Showing papers in "Journal of Hypertension in 1983"

The relationship of blood pressure to diet and lifestyle in two religious populations.

Abstract: Enalapril, a long-acting, non-sulfhydryl, angiotensin converting enzyme (ACE) inhibitor, is well absorbed after oral administration, and hydrolised to its bioactive form, enalaprilic acid (EA). Administration with food does not affect its bioavailability; elimination is predominantly renal. Peak serum EA concentrations occur 4 h after an oral dose; its serum half-life is approximately 35 h, and steady state is achieved by the fourth day of treatment. Enalapril controls blood pressure in essential and renovascular hypertension without affecting heart rate or cardiovascular reflexes. It also decreases serum concentrations of ACE (for greater than 24 h), angiotensin II and aldosterone, and increases plasma renin activity. Once and twice-daily regimens are equally effective. In patients with congestive heart failure refractory to digitalis and diuretics, enalapril increases cardiac output and decreases pulmonary capillary wedge pressure. Long-term treatment produces improvement in NYHA functional classification, exercise capacity and ejection fraction. Human experience to date indicates that enalapril is safe and well tolerated.

Circulatory and sympatho-adrenal responses to stress in borderline and established hypertension.

Abstract: Responses to mental stress [a colour word test (CWT), orthostatic testing (ORT) and a cold pressor test (CPT) were studied in 33 subjects with essential hypertension (EHT), 16 subjects with borderline hypertension (BHT) and 17 age and sex-matched normotensive controls (NT). Venous plasma noradrenaline (NA) was similar in all groups. CWT induced marked circulatory responses and metabolic activation with minor increases in NA. Circulatory and NA responses to ORT and CPT were similar in all groups. CWT elevated diastolic blood pressure more in BHT and tended to elevate HR more in EHT and BHT than in NT. Plasma adrenaline (ADR) tended to be higher in BHT and increased during all provocations in EHT and BHT but not in NT. Early hypertension appears to be associated with enhanced cardiovascular and sympatho-adrenal reactivity (resembling a hypothalamic defence reaction) which is revealed by mental stress, rather than stimuli such as ORT or CPT. Venous plasma NA has limitations in defining neurogenic alterations in hypertension since it reflects poorly sympathetic activity in the organs responsible for pressor responses to emotional stimuli. Plasma ADR is more valuable in this respect.

Haemodynamic effects of nifedipine in essential hypertension at rest and during exercise.

Abstract: Fifteen males with previously untreated essential hypertension in WHO stage I, aged 20-64 years were studied on an outpatient basis. Oxygen consumption, heart rate, cardiac in a in a supine and sitting position and during steady state work at 50, 100 and 150 W. Following the haemodynamic study, nifedipine (long-acting form) 40-80 mg daily was given as the sole drug for 3-12 months (mean 11 months) whereupon the haemodynamic study was repeated. Systolic, diastolic and mean arterial pressures fell about 17% at rest supine and sitting and from 15 to 10% at the three different workloads (P less than 0.001). All but one patient demonstrated a fall in mean arterial pressure of 10 mmHg or more. The fall in pressure was associated with a statistically significant (P less than 0.05) reduction in total peripheral resistance (17% during rest and 10 to 16% during exercise). There were no statistically significant changes in oxygen consumption, heart rate, cardiac index or stroke index.

The effect of a new calcium channel blocker nicardipine on 24-hour ambulatory blood pressure and the pressor response to isometric and dynamic exercise.

Abstract: We have assessed the potential antihypertensive effect of a new slow channel blocker, nicardipine, in a group of patients with essential hypertension. Fourteen patients completed a study using the 'Oxford' system for recording blood pressure during free ambulation and physiological testing. An initial 24-h recording was performed on no treatment and repeated following chronic therapy with 40 mg b.d. of nicardipine. During each recording, the patients performed isometric and dynamic exercise according to a standardized protocol. Within-patient comparisons of consecutive mean hourly systolic and diastolic blood pressures showed a reduction throughout the 24 h during nicardipine therapy. The reduction in blood pressure was also maintained at the peaks of isometric and dynamic exercise. Side-effects were encountered frequently and led to four patient withdrawals. Nicardipine appears to be effective in reducing blood pressure although the frequency of encountered side-effects may limit its usefulness as a first-line antihypertensive agent.

Correlations and otherwise between blood pressure, cardiac mass and resistance vessel characteristics in hypertensive, normotensive and hypertensive/normotensive hybrid rats.

Abstract: We have measured heart weight and properties of 150-200 microns mesenteric resistance vessels from spontaneously hypertensive (SHR), Wistar-Kyoto (WKY), two-kidney, one clip Goldblatt renal hypertensive (RHR) and outbred Wistar rats, as well as in SHR/WKY F2-hybrid rats. All rats were 14-weeks-old. In the SHRs, WKYs, RHRs and Wistars the mean blood pressures (measured intra-arterially) were, respectively: 136, 111, 164 and 100 mmHg. In the SHR/WKYs the systolic blood pressures (measured regularly over a two-week period by the tail cuff method) were normally distributed between the values obtained from control SHRs and WKYs. Relative heart weight and resistance vessel media thickness/lumen diameter ratio correlated (P less than 0.001) with blood pressure between SHRs, WKYs, RHRs and Wistars; however, no significant correlation was seen in SHR/WKYs. By contrast, the calcium sensitivity of the resistance vessel noradrenaline response did correlate (P less than 0.01) with blood pressure in the SHR/WKYs, but did not correlate between the pure strains (calcium sensitivity of the SHR and Wistar vessels was similar, but higher than that of the WKY vessels; induction of renal hypertension did not affect calcium sensitivity). The results suggest that although the cardiac enlargement and increased resistance vessel media/lumen ratio of 14-week SHRs may be advantageous for these animals, these structural abnormalities may not be primary causes of the hypertension. Furthermore, the results indicate that it is the WKYs which are abnormal in having a low calcium sensitivity of their resistance vessels, but suggest also that this reduced sensitivity may be associated with mechanisms which help to keep the WKYs normotensive.

Cardiac and haemodynamic effects of enalapril.

Abstract: The haemodynamic effects of enalapril were evaluated by sequential radionuclide studies in 10 patients followed for three to seven months. The pattern of response was remarkably similar to that of angiotensin antagonists and other oral converting enzyme inhibitors; it consisted of a reduction in peripheral resistance, minimal blood volume changes and no significant increase in either cardiac output or heart rate. The haemodynamic and neurohumoral responses to upright tilt remained normal, despite the lack of supine tachycardia in response to peripheral vasodilation. The pattern of response suggests that the haemodynamic effects of enalapril resulted from interference with angiotensin II (AII) generation rather than from a direct drug effect. Serial echocardiographic studies showed a significant regression in left ventricular (LV) hypertrophy in six out of seven hypertensive patients followed sequentially for three to seven months. Ventricular performance was well preserved despite the reduction in ventricular mass, as indicated by maintenance of the normal relationship of LV fractional shortening (% Sh) to LV end-systolic stress.

Rapidly reversible albumin and beta 2-microglobulin hyperexcretion in recent severe essential hypertension.

Abstract: Seven young patients with newly diagnosed severe hypertension were studied for one week. The mean age was 34.9 years (range 28-44). The mean initial values +/- s.d. for systolic and diastolic pressures were 223 +/- 27 and 141 +/- 8 mmHg, respectively. Secondary hypertension was excluded by conventional methods and serum creatinine was normal. A pronounced but quite variably elevated albumin excretion 440 +/- 448 micrograms/min (mean +/- s.d.) and a moderately increased beta 2-microglobulin excretion 3.06 +/- 3.29 micrograms/min was noted before treatment. The abnormal albumin excretion with ensuing fall in blood pressure was rapidly and almost completely reversible in all but one patient during conventional treatment and the increased beta 2-microglobulin excretion was totally reversible in all but one patient. Both albumin and beta 2-microglobulin excretion rate were positively correlated to arterial pressures in all patients. Thus glomerular and to some extent tubular protein handling were both affected in untreated patients, but rapidly reversible during initial antihypertensive treatment. The data indicate that the beta 2-microglobulin hyperexcretion is secondary to enhanced filtration of plasma protein saturating the tubular reabsorption capacity, while the hyperexcretion of albumin is mainly due to the increased filtration pressure per se, though other factors may be partly responsible.

Arterial wall renin.

Abstract: Aortic homogenates contain proteolytic enzymes which will release angiotensin I (AI) from renin substrate. Some of these are active at low pH and are probably unrelated to renin. Renin-like activity in the rat measured at the optimum pH of 6.5 is altered in parallel with plasma renin in a wide variety of situations. The two diverge only in non-steady state situations. Studies have therefore been carried out after bilateral nephrectomy and after the injection of renal renin into nephrectomized rats. In each case aortic renin-like activity was cleared much more slowly than plasma renin, and the blood pressure change was related to aortic renin-like activity rather than to plasma renin. The blood pressure response to the converting enzyme inhibitor teprotide was also related to the former rather than the latter. Immunofluorescent studies of the aorta and the intrasplenic arteries from rats injected with mouse renin showed that renin was taken up predominantly into the media and persisted at this site. Thus, the uptake of renal renin from plasma by both large and small arteries is probably an important step in the physiology of the renin-angiotensin system and mediates renin-induced changes in peripheral resistance and blood pressure. However, we have no evidence for the hypothesis that selective accumulation of renin in the resistance vessel walls causes hypertension when circulating levels of renin are normal.

Relationship of antihypertensive effect of enalapril to serum MK-422 levels and angiotensin converting enzyme inhibition

Abstract: In hypertensive patients the time courses for the rise in serum MK-422 level, and fall in both angiotensin converting enzyme (ACE) activity and blood pressure after 10 mg of enalapril were very similar. A close relationship between serum MK-422 levels and percentage ACE inhibition could be demonstrated and the acute fall in blood pressure showed a good correlation with either measurement. With chronic administration, serum MK-422 levels increased linearly with the dose of enalapril. As in the acute study, close relationships between the serum MK-422 level and ACE inhibition, and between either measurement and the fall in blood pressure, could be demonstrated after chronic enalapril administration. However, when compared to the acute response, the ACE inhibition dose-response line was shifted to the right after chronic enalapril therapy suggesting that enalapril may lead to ACE induction in humans. This did not appear to influence significantly the blood pressure lowering effect of enalapril or the relationship between ACE inhibition and the hypotensive effect.

Effects of natural oestrogen therapy on blood pressure and renin-angiotensin system in normotensive and hypertensive menopausal women.

Abstract: The blood pressure level and the renin-angiotensin system were investigated in 24 menopausal women (12 normotensive and 12 hypertensive) before, during and after six months of treatment with either oestradiol or trisekvens (sequential preparation containing oestradiol, oestriol and norethisterone acetate). In the normotensive women no significant alterations in systolic or diastolic blood pressure were found during treatment for six months. In the hypertensive women systolic blood pressure fell significantly during treatment with oestradiol as well as with trisekvens, while diastolic pressure did not change. All individual variations of blood pressure were small. The plasma concentrations of renin, angiotensin II and aldosterone remained unchanged during the treatments. A statistically significant increase in plasma renin substrate concentration was observed in all groups with the exception of the normotensive women treated with oestradiol. Menopausal symptoms in hypertensive women may safely be treated with natural oestrogens on the same indications as used for normotensive women.

Regulation of angiotensin converting enzyme.

Abstract: Angiotensin converting enzyme (ACE;EC 3.4.15.1), or kininase II, was studied in serum, cultured endothelial cells from cord artery, in macrophages of humans, and in serum and purified plasma membranes of rats following treatment with inducers of ACE biosynthesis. ACE activity was measured in biological fluids with an enzyme kinetic method employing synthetic 1-hipp-1-his-l-leu tripeptide as a substrate, and with a new method using 125I-labelled specific inhibitor of ACE as a sensitive probe for ACE binding sites. The latter technique also proved suitable for the quantification of ACE in cells. Anti-human ACE antibody was employed for immunofluorescence studies in human cells. Dexamethasone treatment caused an increase in ACE in cultured human endothelial cells, macrophages and in rat pulmonary plasma membranes, but failed to increase serum ACE activity in rats. Captopril and enalapril treatment of hypertensive patients increased total serum ACE, the increase being evident after removal of the active drug from the serum by prolonged storage or chloramine T treatment (captopril) or by dialysis (enalapril). Captopril increased the ACE content of endothelial cells and macrophages. Macrophages appeared sensitive to captopril induction of ACE biosynthesis after pre-stimulation with Escherichia coli lipopolysaccharide. Dexamethasone treatment potentiated the known induction of ACE in rat pulmonary tissue. Thus ACE biosynthesis may be enhanced by three categories of treatment: (1) glucocorticoid; (2) macrophage activation; (3) ACE inhibitors. The precise mechanism of ACE induction and its possible biological relevance await further clarification.

Homologous radio-immunoassay of human plasma dopamine-beta-hydroxylase: analysis of homospecific activity, circulating plasma pool and intergroup differences based on race, blood pressure and cardiac function.

Abstract: We used a homologous human dopamine-beta-hydroxylase (DBH) radio-immunoassay (RIA) to explore reported differences in plasma DBH enzymatic activity among patient groups stratified for race, blood pressure and cardiac function, as well as to determine plasma immunoreactive DBH protein pool and the relative activity of the enzyme in plasma versus human chromaffin tissue storage vesicles. Plasma DBH activity was lower in patients with congestive heart failure than in control subjects (19.9 +/- 4.0 versus 34.4 +/- 5.9 iu/l, P less than 0.05), paralleled by lower immunoreactive plasma DBH protein concentration (3.50 +/- 0.73 versus 6.34 +/- 1.05 micrograms/ml, P less than 0.05). All subject groups had similar plasma DBH homospecific activity (plasma DBH enzymatic activity/immunoreactive plasma DBH protein), ranging from 5.03 +/- 0.28 to 5.84 +/- 0.44 iu/mg. For the entire subject group, there was a significant relationship between plasma DBH activity and plasma DBH immunoreactive protein (r = 0.89, n = 78, P less than 0.01) from which no subgroup deviated systematically. Black hypertensives had lower plasma DBH activity than white hypertensives (23.0 +/- 5.2 versus 42.9 +/- 4.8 iu/l, P less than 0.01), though their plasma DBH homospecific activities and activity/immunoreactive protein plots were indistinguishable. Total circulating plasma DBH pools were large (from 13.1 +/- 3.7 to 27.5 +/- 4.8 mg).(ABSTRACT TRUNCATED AT 250 WORDS)

Prediction of later hypertension following a hypertensive pregnancy.

Abstract: The aim of the present study was to identify factors predicting later hypertension following a hypertensive pregnancy. In the years 1969-1973, 261 out of a total of 17 000 pregnancies were complicated by pre-eclampsia or hypertension in pregnancy. In a follow-up study seven to 12 years later, 238 (91.2%) of these women were investigated. It was discovered that 26.4% of the women had hypertension and 10.1% had borderline hypertension compared with 2 and 6.5% respectively in a group of matched control subjects. A stepwise regression analysis was performed in order to evaluate the association between nine different variables and blood pressure at follow-up. We found that systolic blood pressure in early pregnancy was the single most important factor predicting systolic blood pressure at follow-up (r2 = 0.28). When highest recorded blood pressure before delivery and age were entered into the statistical model, r2 was increased to 0.35 (P less than 0.0001). Unlike previous studies, parity and proteinuria did not add to the predictive power of the analysis. Late hypertension was found in more than 25% of women seven to 12 years after a hypertensive pregnancy. The most important factor associated with later hypertension was blood pressure before pregnancy.

A comparison of minoxidil and hydralazine in non-azotemic hypertensives.

Abstract: This study was undertaken to evaluate whether, after long-term enalapril administration tachyphylaxis to the blockade of angiotensin II (Ang II) generation occurs. After a mean follow-up of 24 months, six patients taking enalapril once daily with or without an associated diuretic were studied for 7 h in hospital. Blood pressure, heart rate, plasma converting enzyme activity, angiotension I (Ang I), Ang II and aldosterone were measured before and 2, 4 and 6 h after the morning dose of enalapril. While blood pressure remained unchanged after drug administration, Ang II and aldosterone levels fell following enalapril to very low levels, similar to those observed during the initial study, at the time of peak effect of enalapril. After enalapril administration, there was no correlation between plasma Ang I and Ang II suggesting that blockade of Ang II generation was complete, excluding the possibility of Ang I related interference with the Ang II measurements. These results indicate that virtually complete angiotension converting enzyme inhibition can still be achieved after prolonged use of enalapril.

Alcohol, personality and predisposition to essential hypertension.

Abstract: The nature of the relationship between alcohol, personality and blood pressure levels was examined in 491 working men who completed detailed questionnaires which included Eysenck's personality inventory. Alcohol had an effect on systolic blood pressure levels independent of all other factors studied. However, in 152 non-smoking moderate to heavy drinkers (greater than 18 g ethanol per day) the extroversion/introversion trait was the most significant predictor of systolic blood pressure levels, and in introverted drinkers the prevalence of hypertension (greater than or equal to 140 mmHg systolic or greater than or equal to 90 mmHg diastolic) was three times that of extroverted drinkers and nine times that of teetotallers. This association between introversion and 'hypertension' was not seen in drinkers who also smoked cigarettes. The interactions between environmental stimuli (alcohol, smoking) and presumably genetically determined personality characteristics may have an important bearing on concepts of essential hypertension and point to new approaches for investigation.

Effect of local infusion of ouabain on human forearm vascular resistance and on response to potassium, verapamil and sodium nitroprusside.

Abstract: The effect of local infusion of ouabain into the forearm vascular bed has been examined in 15 normotensive male volunteers in an attempt to define the nature of the functional abnormalities of the resistance vessels in primary hypertension Ouabain and other drugs were infused into the brachial artery and forearm blood flow was measured by venous occlusion plethysmography Infusion of ouabain at 2 micrograms/min for 1 h caused a 26% reduction in forearm blood flow with a small rise in systemic arterial pressure; the increase in vascular resistance was unaffected by prior treatment with phentolamine After infusion of ouabain the dilator response to potassium was reduced by 33% but the responses to verapamil and sodium nitroprusside were unchanged The results show that acute depression of sodium pump activity by ouabain reproduces the increased resting resistance and impaired response to potassium that are seen in hypertension It does not reproduce the relative enhancement of responsiveness to verapamil that is also observed in the resistance vessels of patients with hypertension and this abnormality must have some other cause

Cardiac regression and blood pressure control in the Dahl rat treated with either enalapril maleate (MK 421, an angiotensin converting enzyme inhibitor) or hydrochlorothiazide.

Abstract: Enalapril maleate (MK 421), and hydrochlorothiazide were used to evaluate the control of hypertension and reversal of myocardial hypertrophy in Dahl sensitive (DS) and Dahl resistant (DR) rats given either a high (8% NaCl) or a low salt (0.4% NaCl) diet. Groups of six-week-old male DS and DR rats were treated with enalapril (15-100 mg/kg/day) in drinking water for eight weeks. Additional comparable groups of DS and DR were also treated with hydrochlorothiazide (60-400 mg/kg/day). Systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR) and heart weight/body weight (Hwt/Bwt) ratio were determined. We observed significant reduction in Hwt/Bwt ratio (P less than 0.001) along with control of SBP and DBP in the DS given a high salt diet treated with either enalapril or hydrochlorothiazide. However, in the DR given a high salt diet, cardiac regression (Hwt/Bwt ratio, P less than 0.05), SBP and DBP (P less than 0.01) reduction were seen only with enalapril. Similarly, cardiac regression (Hwt/Bwt ratio, P less than 0.05) was observed along with reduction of SBP and DBP (P less than 0.001) in the DS given a low salt diet and DR given enalapril. These data indicate that enalapril reduced SBP and DBP in association with cardiac regression in hypertensive and normotensive rats. In contrast, hydrochlorothiazide only reduced SBP, DBP and caused cardiac reversal (Hwt/Bwt ratio) in DS placed on a high salt diet.

Enalapril (MK421) in the treatment of hypertension with renal artery stenosis

Abstract: The converting enzyme inhibitor, enalapril, was given to 20 hypertensive patients with renal artery stenosis in a single daily dose of 10-40 mg. Enalapril effectively controlled hypertension long-term, and only two of the 20 patients required concomitant diuretic treatment. The blood pressure reduction 6 h after the first dose of enalapril was significantly related to pre-treatment plasma concentrations of active renin and angiotensin II (AII), and to the concurrent fall in AII. Blood pressure fell further with continued treatment; the long-term reduction was not significantly related to pretreatment plasma renin or angiotensin II. At three months, 24 h after the last dose of enalapril, blood pressure, plasma AII and converting enzyme activity remained low, and active renin and angiotensin I (AI) high; 6 h after dosing, AII had, however, fallen further. During prolonged therapy, the increase of active renin was proportionately greater than that of angiotensin I. Enalapril alone caused a long-term reduction in exchangeable sodium, with slight increases in serum potassium, creatinine and urea. Enalapril alone did not impair overall renal function in five patients with bilateral renal lesions despite effective blood pressure reduction. Enalapril was well tolerated with no serious side-effects. Enalapril given once daily is effective in controlling hypertension associated with renal artery stenosis.

Blood pressure and pressor mechanisms during alcohol withdrawal.

Abstract: Blood pressure, alcohol withdrawal symptoms and plasma levels of cortisol, aldosterone and renin activity and serum dopamine beta-hydroxylase concentrations were measured in 65 alcoholics on the first and fourth days after admission for detoxification. On the day after admission blood pressure was elevated (greater than 140/90 mmHg) in 32 patients (49%) and was 160/95 mmHg or more in 21 (32%). Plasma renin activity was elevated in 41 patients and plasma aldosterone concentration in 14, but neither correlated with blood pressure. Plasma cortisol levels were elevated in 13 patients and were positively correlated with systolic blood pressure. Blood pressure and all biochemical measures fell significantly by the fourth day while urine volume and sodium output, low on admission, increased significantly. Urinary metanephrine levels were elevated in four of 31 patients in whom they were measured on admission. Alcohol withdrawal was accompanied by raised blood pressure and high plasma concentrations of cortisol, renin and aldosterone but only plasma cortisol concentrations and withdrawal symptoms were significantly related to blood pressure.

Renal blood flow and glomerular filtration rate in renal wrap hypertension in rabbits.

Abstract: Serial measurements of mean arterial pressure and glomerular filtration rate (GFR) were made in rabbits before and 10, 28 and 56 days after bilateral renal cellophane wrap (n = 8) or sham operation (n = 6). No significant changes were seen 10 days after renal wrap, but by 28 days GFR was reduced by 50 +/- 3% and mean arterial pressure had risen by 42 +/- 5 mmHg. No significant further changes occurred over the subsequent month. Changes in plasma renin activity after renal wrapping were not significantly different to those seen after sham operation. In a separate series of experiments, renal extraction ratio of para-aminohippurate (PAH), 28 days after renal wrap, averaged 63 +/- 4% (n = 6) compared to 83 +/- 2% (n = 5) after sham operation. Calculated renal blood flow of the hypertensive rabbits was only about 40% of that in the sham operated rabbits. Thus large reductions in GFR, renal blood flow and PAH extraction ratio occurred following bilateral renal wrapping and these changes may reflect compression of the kidney by the cellophane induced fibrous capsule. These reductions occurred concomitantly with the rise in arterial blood pressure.

The angiotensin conver­ting enzyme inhibitor enalapril and its effects on renal function

Abstract: The renal effects of the new angiotensin converting enzyme inhibitor enalapril (MK-421) and of its active metabolite MK-422, were investigated in patients with essential hypertension. Together with a reduction in blood pressure, renal blood flow increased after intravenous injection of MK-422. Glomerular filtration as well as fractional sodium excretion increased. The latter was explained by the inhibition of both proximal and distal tubular sodium reabsorption. During oral enalapril therapy renal blood flow remained elevated, whereas glomerular filtration did not differ significantly from pretreatment values. Body weight fell after 12 weeks of therapy, a possible consequence of the 'diuretic' effect of enalapril which may contribute to the antihypertensive action of the drug. In conclusion, enalapril had either no, or even beneficial, effects on renal function.

Does potassium lower blood pressure by increasing sodium excretion? A metabolic study in patients with mild to moderate essential hypertension.

Abstract: Potassium chloride (96 mmol potassium/day) in the form of 12 Slow K tablets/day in 10 patients on an intake of 150 mmol sodium and 80 mmol potassium produced a cumulative sodium loss of 110 mmol by the 12th day of potassium supplementation. At the same time there was attenuation of the expected increase in plasma renin activity appropriate for such a sodium loss. The lack of rise in plasma renin activity and hence angiotensin II combined with sodium loss may account at least in part for the observed blood pressure fall. No change in ouabain-sensitive or total white cell sodium efflux rate constant was found. An effect of an increase in plasma potassium on the sodium pump cannot be excluded as the white cell sodium efflux rate constant was measured in a fixed external potassium concentration. There was no evidence from plasma noradrenaline measurements that increasing potassium intake reduces sympathetic activity in the resting state.

Relation of blood pressure with body and plasma electrolytes in Conn's syndrome.

Abstract: Thirty-four patients with untreated Conn's syndrome were studied in a metabolic ward. The final diagnosis in each case was based on the finding and removal of an adrenal cortical adenoma with histological features typical of the disorder. Compared with 34 age and sex-matched normal controls the untreated patients had increased plasma aldosterone concentration, increased blood pressure (183/112 mmHg), increased exchangeable sodium (116.7% of normal), hypokalaemia and increased plasma sodium concentration. Exchangeable potassium was lower than normal and plasma concentrations of active renin, total renin and angiotensin II were lower than normal mean values. Arterial pressure correlated significantly and positively with plasma and exchangeable sodium and there was a significant negative correlation with plasma potassium concentration. Partial regression analysis showed that the relation of exchangeable sodium with blood pressure did not depend on age or renal function but that the relation of blood pressure and plasma potassium could be attributed to the correlation of exchangeable sodium and blood pressure. Multiple regression analysis suggested that exchangeable and plasma sodium were the most important determinants of blood pressure in untreated patients. Spironolactone, amiloride and surgical removal of the adenoma corrected the electrolyte abnormality and usually lowered blood pressure. The fall in exchangeable sodium was related to the fall in blood pressure. The pattern of correlation found by multiple regression analysis in postoperative patients was similar to that in normal subjects. The findings are relevant to some of the mechanisms proposed for the hypertension of mineralocorticoid excess.

Clinical biochemical and haemodynamic correlates of sodium sensitivity in essential hypertension.

Abstract: Factors contributing to the blood pressure (BP) response to changes in dietary sodium intake were studied in 25 patients with essential hypertension (EH) Relevant clinical, biochemical and haemodynamic variables were measured after two weeks on a low sodium diet (LS, 50 mmol) and after two weeks on a high sodium diet (HS, 300 mmol) BP was significantly higher during HS The difference in mean arterial pressure between HS and LS (delta MAP) was taken as a measure of sodium sensitivity delta MAP was directly related to age, initial BP, plasma noradrenaline during HS and changes in forearm vascular resistance It was indirectly related to plasma aldosterone during LS No correlation was found with renin or with the excretion of urinary kallikrein It is concluded that sodium sensitivity in EH is related to age and blood pressure and is predominantly mediated by changes in vascular resistance to which aldosterone and adrenergic mechanisms are likely to contribute

Membrane abnormalities occur in vascular smooth muscle but not in non-vascular smooth muscle from rats with deoxycorticosterone-salt induced hypertension.

Abstract: Microsomal fractions were isolated from the smooth muscle of gastric fundus, vasa deferentia and mesenteric arteries of rats made hypertensive by deoxycorticosterone-salt treatment. Several enzymatic activities, Ca2+ binding and ATP-dependent Ca2+ accumulation of the microsomal fractions from these hypertensive rats were compared with those from the control of rats which remained normotensive under similar treatment. Altered membrane properties were observed in microsomal fractions isolated from vascular smooth muscle but not in those isolated from non-vascular smooth muscles in this form of experimental hypertension. These alterations included decreased Mg2+ ATPase activity, enhanced alkaline phosphatase activity, decreased Ca2+ binding in the absence of ATP and decreased ATP-dependent Ca2+ accumulation. This result is in contrast to our previous findings that decreased ATP-dependent Ca2+ accumulation was observed in microsomal fraction isolated from non-vascular smooth muscles of rats with genetic hypertension. The present study, together with our previous findings, support the contention that altered Ca2+ handling by vascular smooth muscle is associated with the pathogenesis of hypertension, whereas altered Ca2+ handling by non-vascular smooth muscles previously observed in spontaneous hypertension may be associated with genetic factors not related to hypertension.

Na-K-ATPase in single nephron segments of hypertension-prone rats.

Abstract: The mechanism of action of angiotensin converting enzyme (ACE) inhibitors to lower blood pressure remains unclear, but the weight of available data favour peripheral blockade of the formation of angiotensin II (AII). Previous work in rats has shown that the prodrug ACE inhibitor, enalapril (MK-421), lowered blood pressure most effectively when PRA was elevated [sodium deficiency, two-kidney, one figure 8 hypertension, diuretic-treated spontaneously hypertensive rats (SHR)]. In sodium-deficient rats, the enalapril-sensitive component of the blood pressure was greatly reduced after salt loading, and nephrectomy blocked the antihypertensive response to enalapril in SHR. In the present study, further support that the mechanism of action of enalapril involves a reduction in AII has been obtained from rats made hypertensive by continuous intravenous (i.v.) AII infusion for 10 days. Enalapril administered for seven days did not significantly lower blood pressure, suggesting that there were no important non-angiotensin mechanisms (such as bradykinin potentiation) involved in its action. From earlier studies in SHR, the time course for blockade of angiotensin I (AI) pressor responses and the blood pressure reduction did not correspond, suggesting a tissue site of action. In the present studies in adult SHR, a central site of action was ruled out since the parent inhibitor, enalaprilic acid (MK-422), injected into the brain ventricles did not acutely reduce blood pressure. An interaction of enalaprilic acid with the sympathetic nervous system was evaluated in dogs in which adrenergic activity was enhanced as a result of diuretic-induced renin release. Enlaprilic acid did not alter the enhanced hindquarter vasoconstrictor responses to sympathetic nerve stimulation. Enalapril increased renal blood flow, glomerular filtration rate and sodium excretion. The mechanism of the natriuresis in dogs probably involves several mechanisms including a decrease in aldosterone biosynthesis, changes in renal function (glomerular filtration rate and renal blood flow) and possibly blockade of a direct tubular effect of AII on sodium reabsorption. Enalaprlic acid was also studied in a closed chest dog model of acute left ventricular (LV) failure caused by embolization via the left main coronary artery with 50 microns plastic microspheres. Enalaprilic acid at 100 micrograms/kg i.v. reduced preload, afterload and improved LV performance without changing the heart rate. In conclusion, enalapril the prodrug, and enalaprilic acid the active inhibitor, are potentially useful in the treatment of hypertension and LV failure.(ABSTRACT TRUNCATED AT 250 WORDS)