Showing papers in "Journal of Hypertension in 1989"

Prognostic value of ambulatory blood pressure measurements: further analyses.

Abstract: The value of ambulatory systolic blood pressure as a predictor of the development of cardiovascular complications was investigated in a sample of 761 hypertensive patients who had undergone ambulatory blood pressure monitoring and who were followed for an average of 5.5 years. Of the 695 patients without prior cardiovascular events at entry into the study, 11% subsequently experienced an event during the follow-up period (up to 10 years) compared to 48% of the 102 patients with a prior cardiovascular event. For each patient, a 'predicted' ambulatory systolic blood pressure was calculated, using the patient's office systolic blood pressure and the equation derived from regressing ambulatory on office blood pressure for the entire sample. By subtracting the predicted from the observed ambulatory pressure, a 'residual' ambulatory systolic blood pressure was derived for each patient, as a measure of that portion of the ambulatory pressure that could not be predicted from the office pressure. We used a Cox proportional hazards model to analyse the independent effect of each of the following patient characteristics at entry on the occurrence of subsequent cardiovascular events: sex, age, ECG evidence of left ventricular hypertrophy, hypertensive retinopathy, ambulatory systolic blood pressure, office systolic blood pressure, residual ambulatory systolic blood pressure and subsequent drug therapy. In both groups, with and without a prior cardiovascular event, women, younger patients and those with lower residual ambulatory systolic blood pressure tended to have longer periods of survival without new cardiovascular events. In the group without prior cardiovascular events, a lower office systolic blood pressure and the absence of advanced ECG evidence of left ventricular hypertrophy were also independently predictive of longer event-free survival.(ABSTRACT TRUNCATED AT 250 WORDS)

Metabolic effects of diltiazem and atenolol: results from a randomized, double-blind study with parallel groups

Abstract: In a randomized, double-blind study (n = 58) with parallel groups, the effects of diltiazem (mean dose 329 mg/day) and atenolol (mean dose 67 mg/day) on carbohydrate and lipoprotein metabolism in hypertensive patients were compared. The mean systolic blood pressure (SBP)/diastolic blood pressure (DBP) reductions in the supine position were similar and satisfactory, 9/11 and 11/9 mmHg during atenolol and diltiazem treatment, respectively. Insulin-mediated glucose uptake, measured with the euglycaemic insulin clamp technique, decreased during atenolol treatment, from 7.1 to 5.6 mg/kg per min (P = 0.05). but not during treatment with diltiazem (initial value 6.8, final value 6.7 mg/kg per min; P greater than 0.8). Treatment differences between groups were statistically significant (P less than 0.05). During atenolol treatment there was a slight but significant increase in plasma glucose in the fasting state (P less than 0.05) and at the end of an intravenous glucose tolerance test (IVGTT; P less than 0.01), and in plasma insulin at the end of IVGTT (P less than 0.05). Despite increased insulin resistance the increase in insulin response was small, suggesting inhibition of insulin release. The insulin peak was decreased by 13% during diltiazem treatment (P less than 0.05). The concentrations of very-low and low-density lipoprotein triglycerides increased, whereas high-density lipoprotein cholesterol decreased and low-density lipoprotein cholesterol was unaffected during atenolol treatment. In conclusion, there was no difference between the antihypertensive effects of atenolol and diltiazem, but atenolol decreased insulin sensitivity and altered the lipid profile, thus possibly increasing the risk of diabetes mellitus and theoretically reducing the benefits of blood pressure reduction with regard to risk of coronary heart disease.

Spectral analysis of R-R and arterial pressure variabilities to assess sympatho-vagal interaction during mental stress in humans

Abstract: We tested the hypothesis that spectral analysis of the R-R interval and systolic arterial pressure variabilities allows assessment of the dynamic changes in neural control of the cardiovascular system in men undergoing mental stress testing. Mental arithmetic increased the low-frequency components of R-R and systolic arterial pressure, i.e. markers of sympathetic activity to the SA node and the vasculature, respectively; it also decreased the high frequency component of R-R variability, a marker of vagal activity. Spectral analysis of R-R and systolic arterial pressure variabilities may be used in the clinic to test the dynamic effects of mental stress on both sympathetic and vagal activities.

An analysis of spontaneous hypertension in spontaneously hypertensive rats by means of new recombinant inbred strains.

Abstract: The mode of blood pressure inheritance and some genetic markers of spontaneous hypertension were evaluated in a new set of recombinant inbred (RI) strains obtained by crossing of normotensive (BN.lx) and hypertensive (SHR) progenitor strains. Blood pressure values of RI strains were continuously distributed between both progenitor strains, although normotensive strains slightly prevailed. Statistical analysis suggested that there are three major genes and multiple minor genes responsible of the determination of spontaneous hypertension. The association between blood pressure and gene(s) within RT1 complex or gene(s) closely linked to it was found by RI strain analysis. This suggestion was confirmed by the detection of significant difference in blood pressure between SHR and SHR.1N congenic strains. Our results indicate that RT1 complex gene(s) may be involved in the development of high blood pressure.

Development of blood pressure in spontaneously hypertensive rats after withdrawal of long-term treatment related to vascular structure.

Abstract: We have studied the effects of long-term treatment with different antihypertensive drugs on blood pressure and mesenteric resistance vessel structure of spontaneously hypertensive rats (SHR), both during treatment and after withdrawal of treatment. Young SHR were treated from 4 to 24 weeks with five different drugs: perindopril (1.5 mg/kg per day), captopril (60 mg/kg per day), hydralazine (25 mg/kg per day), isradipine (42 mg/kg per day) and metoprolol (130 mg/kg per day). At 24 weeks, 24-h mean blood pressures (MBP), measured invasively, were 121 mmHg (perindopril), 137 mmHg (captopril), 140 mmHg (hydralazine), 149 mmHg (isradipine) and 146 mmHg (metoprolol), compared to control values of 177 mmHg (SHR) and 132 mmHg (Wistar-Kyoto rats, WKY). Mesenteric resistance vessel structure, measured as media:lumen ratio (m:l), was also reduced to different extents: to WKY-level by perindopril (m:l = 4.4%), to midway between SHR- and WKY-levels by captopril, hydralazine and isradipine (m:l = 5.9%), and not at all by metoprolol (m:l = 6.8%). When treatment was discontinued, low MBP (ca 151 mmHg) persisted for 12 weeks in rats treated with the angiotensin converting enzyme inhibitors (perindopril and captopril), but rose rapidly in rats which had received the other treatments. At 3-12 weeks after withdrawal of treatment vascular structure was closely correlated with the blood pressure expected from the SHR- and WKY-control values, as were the left ventricle: body weight ratios. The results suggest that the ability of a drug to control vascular structure during treatment is not in itself a predictor of a persistent effect on blood pressure after withdrawal of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Sexual dimorphism of blood pressure in spontaneously hypertensive rats: effects of anti-androgen treatment

Abstract: The mechanisms resulting in the greater predisposition of male subjects towards hypertension were investigated in different strains of rats with genetic hypertension [spontaneously hypertensive rats of the stroke-prone strain (SHRSP) and spontaneously hypertensive rats (SHR)] and their respective normotensive controls. Blood pressure was reduced in young (9 weeks of age) hypertensive rats by (1) surgical castration, (2) treatment with the testosterone receptor antagonist cyproterone acetate (CPA), which does not elevate testosterone, or (3) with the testosterone receptor antagonist flutamide, which leads to a feedback elevation of gonadotrophic hormones and plasma testosterone. These treatments had no effect on high blood pressure in old hypertensive rats aged 25 weeks. Both androgen receptor antagonists attenuated high blood pressure development when given for the first 10 days after birth. These data clearly relate the sexual dimorphism of hypertension to testosterone produced during male brain maturation in the early phase of hypertension development. Testosterone appears not to contribute directly to the maintenance of high blood pressure in established hypertension.

Multiple pathways of angiotensin production in the blood vessel wall: evidence, possibilities and hypotheses.

Abstract: In summary, multiple pathways of angiotensin production may exist in the blood vessel wall (Fig. 1), in addition to the well described renin--ACE enzymatic axis. It is not known whether these enzymatic pathways represent in vitro phenomena, or authentic in vivo alternate pathways which are activated only when the renin--ACE pathway is blocked, or whether they are operative at all times in the vessel wall. If these multiple pathways are functional, then the vascular angiotensin system may be very complicated, and may vary in different pathophysiological states. Future research in this area is likely to yield important and novel information on the in vivo pathways of production and function of vascular angiotensin.

Hypertension in blacks: psychosocial and biological perspectives.

Abstract: The extraordinarily high rate of hypertension in blacks remains a significant public health issue in most industrialized societies. Research has focused on the investigation of racial differences in biological, nutritional, behavioural and psychological, and social factors in an effort to identify the causes of this high morbidity rate. Thus far, research suggests important racial differences in renal functioning, particularly in sodium metabolism and plasma renin activity, as well as potassium intake and sodium:potassium ratio. Behavioral factors such as anger-coping style and John Henryism, and social factors such as socioeconomic status, socioecological stress, social support, urban-rural residence, and family interaction patterns have also been identified as potential contributors. Finally, emerging research paradigms such as laboratory stress reactivity and 24-h ambulatory monitoring of blood pressure may provide promising leads about the interaction between these effects and hypertension in black populations.

The hypertensive effect of synthetic glucocorticoids in man: role of sodium and volume.

Abstract: In previous studies, administration of adrenocorticotrophin (ACTH; 0.5 mg i.m. b.d. for 5 days) to normal subjects produced an adrenally dependent rise in blood pressure (BP) of some 20mmHg, accompanied by an increase in cardiac output and an increase in plasma volume [1]. The BP and metabolic effects of ACTH (increase in plasma glucose, fall in eosinophils, increase in body weight and urine sodium retention) were reproduced by infusion of the glucocorticoid (GC) cortisol at rates (6-8mg/h) which reproduced the blood concentrations of the steroid achieved with ACTH administration [2]. Oral administration (hydrocortisone 200 mg daily) produced similar changes qualitatively, although the cortisol concentrations and increase in pressure (12mmHg) were less. Plasma volume was increased [3]. To determine the role of urine sodium retention and plasma volume expansion in the hypertension, we gave synthetic steroids to six normal subjects for 5 days, at doses which were calculated to be similar for GC activity, but which had little or no mineralocorticoid (MC) activity. Prednisolone (40mg/day), methylprednisolone (32mg/day), triamcinolone (40mg/day) and dexamethasone (8mg/day) all produced equivalent GC effects (increase in plasma glucose, increase in total white cell count, fall in direct eosinophil count). There were no MC effects with any of the steroids. Body weight did not increase and urinary sodium excretion increased rather than decreased. Plasma volume (125I human serum albumin) and haematocrit were unchanged. BP rose with all four steroids: systolic BP rose by 13mmHg with prednisolone, by 9mmHg with methylprednisolone, by lOmmHg with triamcinolone, and by 6mmHg with dexamethasone. Diastolic BP increases were 8, 11, 8 and 7mmHg, respectively. Thus, neither MC activity nor an increase in plasma volume is essential for steroids to induce an increase in blood pressure. Therefore, screening of synthetic GCs to minimize MC activity will not prevent hypertensive complications.

Clinical evaluation of semiautomatic and automatic devices for home blood pressure measurement: comparison between cuff-oscillometric and microphone methods.

Abstract: The accuracy and reliability of blood pressure (BP) values were evaluated by comparing values obtained with eight automatic or semiautomatic devices designed for home BP measurement (four microphone devices based on the Korotkoff-sound technique and four cuff-oscillometric devices) with those obtain

Pulse pressure and echocardiographic findings in essential hypertension.

Abstract: Blood pressure, carotid-femoral pulse wave velocity and cardiac mass as judged on echocardiography were evaluated in 11 normal subjects and 36 patients with sustained essential hypertension of similar age. The hypertensive patients were divided into two groups of similar age, weight, height and mean arterial pressure: patients in the first group (Group I) had a pulse pressure inferior to 60 mmHg and in the second group (Group II) had a pulse pressure equal or superior to this value. Group II patients had significant higher values for cardiac mass (148.8 +/- 44.3 vs 116.3 +/- 19.8 g/m2; P less than 0.01) (+/- 1 s.d.) than Group I, while mean arterial pressure and pulse wave velocity were similar in the two groups. Stroke volume was significantly higher in Group II than in normal subjects (99.5 +/- 17.1 versus 82.7 +/- 16.9 ml; P less than 0.05). The study findings suggested that the increased pulse pressure in hypertensive patients might influence the development of cardiac hypertrophy independently of mean arterial pressure and aortic distensibility. The increased pulse pressure could reflect a disturbance between ventricular ejection and impedance affecting the ventricle with a resulting increase in pulsatile energy losses and further increase in cardiac mass.

Effects of complete renal denervation and selective afferent renal denervation on the hypertension induced by intrarenal norepinephrine infusion in conscious rats.

Abstract: To test the hypothesis that continuous intrarenal norepinephrine (NE) infusions produce hypertension via activation of afferent renal nerves (ARN), rats were subjected to complete renal denervation (RN-x), selective renal deafferentation (ARN-x) or sham surgery, prior to infusion of NE. In the pre-infusion period, mean arterial pressure (MAP) was significantly lower in RN-x than in ARN-x or sham-operated rats. Plasma renin concentration (PRC) was significantly reduced following ARN-x, but not RN-x. During 5-day intrarenal infusions of 4, 12 or 36 micrograms NE/kg per h, MAP rose to similar levels in RN-x and sham-RN-x rats. However, RN-x rats exhibited significantly elevated PRC levels, suggesting that denervation supersensitivity masked the possible effects of RN-x. In sham-RN-x rats, MAP increased significantly more during intrarenal infusion of 12 micrograms NE/kg per h than during intravenous infusion of the same amount. In ARN-x rats, MAP rose to a similar degree during intravenous and intrarenal infusions. The pressor responses in the ARN-x rats, however, were not significantly smaller at any point than those in intact rats. PRC rose to comparable levels in ARN-x and intact rats. Thus, in normotensive rats, efferent renal nerves (ERN) but not ARN are of functional significance in maintaining basal blood pressure. ARN may be involved in the control of renin release. Since neither RN-x nor ARN-x attenuated the development of hypertension, renal nerves are not necessary for the full expression of hypertension in this model.

Twenty-four-hour blood pressure is not dependent on endogenous circadian rhythm

Abstract: The effects of shifted working and sleeping phases on the diurnal blood pressure rhythm were investigated in 15 physically working industrial shift workers at a slowly rotated three-shift system. Ambulatory 24-h blood pressure monitoring was performed during the morning and night shifts. In the two

Clinical evaluation of the Colin ABPM 630 at rest and during exercise: an ambulatory blood pressure monitor with gas-powered cuff inflation.

Abstract: The Colin ABPM 630 is a silent, gas-powered (CO2) ambulatory blood pressure monitor which uses both ausculatory and/or oscillometric methods to measure blood pressure. We compared simultaneous, same-arm blood pressures obtained with the monitor with those made by two blinded, skilled clinicians using a mercury column and teaching stethoscope. In a second study, the monitor readings were also compared with opposite-arm intra-arterial recordings of blood pressure. The group mean systolic blood pressures obtained by the Colin monitor via the Korotkoff mode were almost identical to the mercury column readings (127.8 +/- 19.4 versus 128.1 +/- 19.3 mmHg, P = NS) and the limit of agreement (2 standard deviations) for the differences in the two methods was +/- 9 mmHg. The diastolic blood pressure obtained by the Colin monitor was significantly lower than the clinician's readings (-6.0 +/- 5.9 mmHg, P less than 0.0001). Similar findings were obtained with the oscillometric mode, however, the mean systolic blood pressure given by the monitor was slightly higher than that given by the mercury column (1.9 +/- 4.5 mmHg, P less than 0.001). In contrast to the mercury column comparisons, the mean diastolic blood pressure obtained with the monitor was nearly the same as the mean intra-arterial diastolic blood pressure for both the Korotkoff (0.1 +/- 5.6 mmHg) and the oscillometric modes (1.2 +/- 6.3 mmHg). During 100-watt bicycle exercise, there was a considerably greater scatter in the individual comparisons of the monitor and intra-arterial blood pressure than that seen in the measurements at rest, but the group means were again similar.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparative studies of tissue inhibition by angiotensin converting enzyme inhibitors

Abstract: There is increasing evidence that inhibition of tissue angiotensin converting enzyme (ACE) is important for the pharmacokinetics and pharmacodynamic effects of ACE inhibitors. Radioligand inhibitor binding methods using 125I-351A and either tissue homogenates or in vitro autoradiography have allowed in vitro and ex vivo quantitation of tissue ACE inhibition by a variety of ACE inhibitors. The rank order of potency against plasma as well as lung, kidney, and cardiac homogenates was quinaprilat = benazeprilat greater than perindoprilat greater than lisinopril greater than enalaprilat greater than fosinoprilat. The highest concentration of ACE in the heart was found in the cardiac valves followed by the right and left atria, then the right and left ventricles. Ex vivo studies showed that after oral administration of quinapril, ACE was inhibited dose-dependently in the lung, kidney, aorta and heart for more than 24h. Tissue bioavailability of the inhibitor is also an important determinant of tissue ACE inhibition. Perindopril crossed the blood-brain barrier and inhibited brain ACE at high doses, but after equivalent doses of quinapril no brain ACE inhibition could be demonstrated. These results suggest that it may be possible to design ACE inhibitors to have specific effects on ACE in different tissues.

Effects of chronic ACE inhibition on cardiac hypertrophy and coronary vascular reserve in spontaneously hypertensive rats with developed hypertension.

Abstract: Left ventricular hypertrophy due to hypertension is associated with a decrease of coronary vascular reserve. We have previously shown that chronic angiotensin converting enzyme (ACE) inhibition prevents cardiac hypertrophy and improves coronary vascular reserve when the treatment is started before appearance of hypertension in spontaneously hypertensive rats (SHR). However, the effects of starting chronic ACE inhibition when hypertension was already developed is not known. The goal of the present study was to assess the effects of chronic ACE inhibition on coronary vascular reserve and on the morphology of the coronary microvasculature when treatment was started after hypertension had developed. For this purpose, one group of SHR was treated from 3-8 months of age with cilazapril, a new ACE inhibitor, and compared with a group treated by placebo. At the end of treatment, cardiac hypertrophy, coronary vascular reserve, density and cross-sectional surface area of the myocardial capillaries (normalized for the myocardial mass) and wall/lumen ratio of the coronary arterioles were determined. Chronic ACE inhibition with cilazapril reduced cardiac hypertrophy and improved by more than 50% coronary vascular reserve in the left and right ventricles. In the left ventricle, the improvement was more pronounced in the subendocardium than in the subepicardium. Cilazapril increased the density and the cross-sectional surface area of the myocardial capillaries and decreased the wall/lumen ratio of the arterioles of the left ventricle. We conclude that chronic ACE inhibition can improve coronary vascular reserve, increase capillary density and capillary cross-sectional surface area and decrease the thickness of the media of coronary arterioles in SHR even when treatment is started after development of hypertension.

Sex steroid hormones are altered in essential hypertension

Abstract: Little is known about the relationship between blood pressure and endogenous sex steroid hormones in patients with essential hypertension. Studies in hypertensive men have described decreased androgens. Men with cardiovascular disease may have estrogen levels which are increased or similar to healthy controls. We measured selected sex steroid hormones in 24 medication-free patients with uncomplicated essential hypertension (diastolic blood pressure less than or equal to 90 mmHg) and 24 normotensive subjects. The groups were equally divided by race, gender, age and weight. Hypertensive men had lower levels of both free and total testosterone and androstenedione than controls. The converse was true for hypertensive women. Androgen levels were similar in blacks and whites regardless of gender or blood pressure. Estradiol levels were higher in hypertensive men and women than controls and in blacks than whites. Levels of luteinizing hormone and sex hormone binding globulin were similar in all subjects. The clinical and pathophysiological significance of our findings merits further investigation.

Circadian rhythm of glomerular fitration rate in normal individuals

Abstract: 1. In a group of 11 normal individuals we measured glomerular filtration rate (GFR) by inulin clearances and effective renal plasma flow (ERPF) by p-aminohippurate clearances during a period of 24 h and a regimen of bedrest, identical food intake per 3 h and normal sleep/wake and light/dark cycles. 2. All subjects had a circadian rhythm for GFR with a maximum of 122 ml/min (SD 22) in the daytime, a minimum of 86 ml/min (SD 12) at night and with a relative amplitude of 33% (SD 15). 3. ERPF had a circadian rhythm with a similar relative amplitude as the GFR rhythm, but with a different phase. Because of this difference in phase, the calculated filtration fraction (GFR/ERPF) followed a circadian rhythm as well. 4. The circadian rhythms of urine volume and sodium excretion were in phase with the GFR rhythm, but the potassium rhythm had a different phase, probably because urinary potassium is largely derived from tubular secretion. 5. Urinary albumin and beta 2-microglobulin excretion had a circadian rhythm in phase with the GFR rhythm. 6. The highest quantity of sodium, water and beta 2-microglobulin was reabsorbed in the daytime; tubular reabsorption, expressed as percentage of the filtered load (fractional reabsorption), had a rhythm with a reversed phase.

Effects of alcohol intake on blood pressure and sympathetic nerve activity in normotensive humans: a preliminary report.

Abstract: Although several epidemiological studies have shown an association between alcohol consumption and high blood pressure, the mechanisms involved in the pressor effect of alcohol are not clear. We hypothesized that alcohol might increase blood pressure at least in part by increasing sympathetic nerve activity. In a double-blind, placebo-controlled study of seven normotensive subjects (mean age +/- s.e.m. 24.0 +/- 1.5 years), we investigated the effects of oral administration of alcohol (0.75 g/kg body weight, diluted in orange juice) or vehicle on arterial blood pressure, heart rate and muscle sympathetic nerve activity, measured directly in the peroneal nerve by microneurography. Plasma ethanol levels increased from 0 (control) to a range of 47.7 +/- 7.6 to 53.3 +/- 5.0 mg/dl 30 min after alcohol intake. This increase in plasma ethanol was accompanied by a significant increase (P less than 0.05) in mean blood pressure, heart rate and sympathetic nerve activity. The vehicle did not affect any of these parameters. Our data suggest that acute oral administration of a moderate dose of alcohol induces a pressure effect through activation of sympathetic nervous outflow.

Blood pressure changes during heavy-resistance exercise.

Abstract: To study the mechanisms of the blood pressure changes during weight-lifting, three hypertensive and five normotensive body-builders underwent continuous intra-arterial monitoring. In two subjects (one normotensive and one hypertensive), intrathoracic and intra-abdominal pressures were also measured. Extremely high blood pressure elevations of up to 345/245 mmHg were observed during the lifts. Squatting caused the highest pressure rises and single-arm curls the lowest. Both the intrathoracic and the intra-abdominal pressures increased greatly during each lift and closely paralleled the changes in intra-arterial pressure. A close correlation was found between the blood pressure increase during the exercise and during a hand-grip test (r = 0.95, P less than 0.001). These results suggest that a pronounced increase in intra-thoracic and intra-abdominal pressures is a major determinant of the blood pressure elevations occurring during weight-lifting. The pressor reflex which accompanies static contractions and the individual baseline blood pressure levels also seem to affect the height of the pressure peaks.

Exogenous glucocorticoid eliminates or reverses circadian blood pressure variations.

Abstract: The effect of glucocorticoid on circadian variations of blood pressure was examined. In untreated patients with essential hypertension, a clear nocturnal fall in blood pressure and heart rate was observed and this was unaffected by combined treatment with antihypertensive drugs. The circadian blood pressure variation in patients with chronic glomerulonephritis (CGN) not receiving glucocorticoid treatment was essentially the same as that in patients with essential hypertension. In both groups there was a positive correlation between blood pressure and heart rate. On the other hand, in patients with CGN and systemic lupus erythematosus (SLE) who were treated with glucocorticoid, there was no nocturnal fall in blood pressure, and often a significant rise. In these patients the blood pressure was lowest in the afternoon and began to rise from then, and during the night, attaining a peak level in the morning. Despite this changed pattern of blood pressure variations, the heart rate in these patients was clearly reduced at night. In 10 patients with CGN and SLE, circadian rhythm of blood pressure and heart rate was examined before and during treatment with prednisolone (40.2 +/- 17.0 mg/day for 58.0 +/- 19.4 days, mean +/- s.d.). Prednisolone abolished the nocturnal fall of blood pressure, while the nocturnal fall of heart rate remained. There was no correlation between blood pressure and heart rate in patients with glucocorticoid treatment. These results suggest that the circadian blood pressure variation is influenced by the hypothalamo-pituitary-adrenal axis, probably through its action on the autonomic nervous system.

Endothelium-dependent relaxation in resistance vessels from the spontaneously hypertensive rats.

Abstract: The endothelium-dependent vasodilator acetylcholine was used to observe relaxation responses of noradrenaline-contracted mesenteric resistance vessels from 3-, 6-, 12- and 18-week-old spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). Relaxation responses were greater than normal in the 3-week-old SHR but the pattern of response was different in the 6-18-week-old SHR compared with the WKY. In these older animals, low concentrations of acetylcholine relaxed SHR and WKY vessels to a similar extent, but high concentrations (greater than 10(-7) mol/l) caused the partially relaxed vessels to contract again. Indomethacin enhanced relaxation in the 12-week-old SHR and reduced the difference between the SHR and WKY. The reduction in acetylcholine-induced, endothelium-dependent relaxation in SHR suggested that a functional change occurred, causing the vessels to release a vasoconstrictor factor that opposes the action of endothelium-derived relaxing factor.

Value of ambulatory blood pressure monitoring in clinical pharmacology.

Abstract: Ambulatory monitoring of blood pressure can improve clinical trials in two ways, first, by the identification and exclusion of those patients in whom the blood pressure is raised only in the clinic environment and second, by improving the repeatability of blood pressure estimations. In 75 subjects the standard deviation of the difference in diastolic pressure between two clinic readings taken a month apart was 12.3 mmHg. On ambulatory monitoring this fell to 6.3 mmHg. Since the number of subjects needed in a trial is related to the square of the standard deviation of the difference, the improved repeatability leads to a substantial reduction in the number of subjects needed. However, to achieve an adequate repeatability, at least 20 blood pressure readings are required per day.

Phenylephrine, vasopressin and angiotensin II as determinants of proto-oncogene and heat-shock protein gene expression in adult rat heart and aorta.

Abstract: The expression of two oncogenes (conc) c-myc and c-fos, coding for nuclear proteins which play a regulatory role in growth and differentiation, and of two genes coding for two heat shock proteins (HSP) 68 (molecular weight 68,000) and 70 (molecular weight 70,000), which have a protective function during stress, have been investigated by Northern blot analysis of the total RNA, extracted from adult rat ventricle and aorta. (1) The two onc transcripts are absent from these tissues but their expression can be enhanced by a pretreatment with cycloheximide. (2) The HSP70 is, in part, constitutive, while HSP68 is not; both are thermo-inducible in an isolated coronary perfused rat heart. (3) The four messenger RNA (mRNA) are expressed in both ventricles and aorta, 1 or 2 hours after i.p. injection of 6 mg/kg phenylephrine or 12 IU/kg of vasopressin. (4) They are also induced by a continuous or discontinuous injection of angiotensin II (7.5 micrograms/kg per min) for 1-2 h, but only in the aorta. The lack of ventricular response to angiotensin II in rat ventricles has been attributed to the lack of angiotensin II receptors in this tissue. This indicates that, in addition to mechanical factors, circulating hormones which have in common the use of the phosphoinositol pathway, may activate the expression of genes coding for regulatory proteins. This may play a role in the genesis of both ventricular and aortic hypertrophy.

Abnormal structure and function of isolated subcutaneous resistance vessels from essential hypertensive patients despite antihypertensive treatment.

Abstract: The morphological and functional characteristics of isolated subcutaneous resistance vessels (about 230 microns internal diameter) from 13 patients treated for essential hypertension for a median period of 14 months and from 15 matched normotensive controls were examined. The blood pressure of the patients and the controls were not significantly different at the time of examination. However, although compared with the controls, the lumen diameter of the vessels from the patients was not significantly different, the media thickness to lumen diameter ratio was 19% greater. Furthermore, although there was no difference in the active pressure response of the vessels from the two groups, the vessels from the patients had a lower sensitivity to calcium, relaxed faster after a contraction and the sensitivity to exogenous noradrenaline shifted more to the left with cocaine. Since the abnormalities found here have previously also been found in vessels from patients with untreated essential hypertension, the study suggests that despite antihypertensive treatment to normotensive levels for about 1 year, some morphological as well as functional characteristics of the resistance arteries are not fully normalized. This could have consequences for the prognosis of essential hypertension.

Endothelin sensitivity and receptor binding in the aorta of spontaneously hypertensive rats.

Abstract: The aim of this study was to determine whether sensitivity to endothelin was greater in isolated aortic rings of spontaneously hypertensive rats (SHR) than in those of normotensive Wistar-Kyoto rats (WKY) and, if so, whether this was due to an increased binding affinity. Adult SHR were more sensitive to endothelin that age-matched WKY, but the maximal tension developed in response to endothelin was significantly lower in SHR than in WKY

Clinical evaluation of the Accutracker II ambulatory blood pressure monitor: assessment of performance in two countries and comparison with sphygmomanometry and intra-arterial blood pressure at rest and during exercise.

Abstract: In order to assess the Accutracker II (Suntech Medical Instruments, Raleigh, North Carolina, USA), a relatively new ambulatory blood pressure (BP) monitor, versus standard forms of BP measurement, we compared same- and contralateral-arm measurements made, via a t-tube connected to a mercury column sphygmomanometer, by two clinicians using a teaching stethoscope and by intra-arterial recordings. Average systolic BP values obtained using the Accutracker II were similar to both the mercury column and intra-arterial determinations, but average diastolic BP values were lower than both the average mercury column (2.8 +/- 4.2 mmHg, P less than 0.001) and intra-arterial measurements (2.0 +/- 4.7 mmHg, P less than 0.02). During isometric exercise and 100-watt bicycle exercise, there were greater limits of agreement for the differences in BP between the Accutracker II and the intra-arterial transducer than were observed for the resting measurements, but these differences were no greater than those observed between intra-arterial and clinician-determined BP measurements. The clinical performance of the Accutracker II was assessed using 119 hypertensive subjects (84 in Norway and 35 in the USA) who wore the monitor for 24 h. While there was good-to-excellent data return in both countries, there were significantly less error codes secondary to excessive arm motion observed in Norway. Our data demonstrate that the Accutracker II is quite accurate compared with both the mercury column and intra-arterial methods of measuring BP, and performs well during 24 h outpatient activities. Our findings also indicate certain geographical differences which may be important in the performance of ambulatory BP-monitoring studies.

Differences in the subjective well-being and symptoms of normotensives, borderline hypertensives and hypertensives.

Abstract: In this study, previously untreated subjects were randomly recruited from a blood pressure screening programme. After repeated measurement of blood pressure levels, the subjects were divided into three groups: normotensives (n=95), borderline hypertensives (n=69) and hypertensives (n=30). Three self-administered standardized questionnaires were used to measure different aspects of subjective well-being and symptoms: the Nottingham Health Profile (NHP), the subjective Symptoms Assessment Profile (SSAP) and the Minor Symptoms Evaluation Profile (MSEP)