Showing papers in "Blood Pressure in 1996"

How smoking affects blood pressure.

Abstract: Omvik P. How smoking affects blood pressure.The addictive effects of smoking are only partly known, but it is likely that hemodynamic effects of tobacco smoking may contribute to the habituation. I...

Controlled Trial of Losartan Given Concomitantly with Different Doses of Hydrochlorothiazide in Hypertensive Patients

Abstract: Ruilope LM, Simpson RL, Toh J, Arcuri KE, Goldberg AI, Sweet CS. Controlled trial of losartran given concomitantly with different doses of hydrochlorothiazide in hypertensive patients.The purpose o...

Physiologic and pharmacologic implications of AT1 versus AT2 receptors.

Abstract: The renin-angiotensin system (RAS) is an important factor in the pathogenesis of cardiovascular diseases, including hypertension and congestive heart failure. The RAS also contributes to media hypertrophy and neointima formation. The recent development of specific, highly selective, nonpeptide angiotensin II (A II)-receptor ligands/antagonists was the basis for the identification of the A II-receptor subtypes, AT1 and AT2, which display a heterogeneous distribution. Virtually all known physiologic actions of A II have been attributed to AT1 receptors; much less is known about AT2 receptors. Cell growth, proliferation, or both are mediated by AT1 receptors, whereas stimulation of AT2 receptors leads to an inhibition of cell proliferation and possibly induces cell differentiation. Under physiologic conditions. AT1 receptors may facilitate angiogenesis while AT2 receptors inhibit it. Under pathophysiologic conditions. AT2 receptors could be up-regulated to control excessive growth mediated in part by AT1 receptors. Characterization of the angiotensin-receptor subtypes has advanced our knowledge of the various functions of A II in the pathogenesis of hypertension and related diseases. It is hoped that eventually we will be able to develop even more specific blocking agents of the pathogenic effects of A II.

The clinical pharmacology of losartan in Japanese subjects and patients

Abstract: The pharmacokinetics and biochemical efficacy of losartan, an orally active nonpeptide angiotensin II (A II)-receptor antagonist, were studied in healthy male volunteers after single oral dose administration (25, 50, 100, or 200 mg) and multiple oral dose administration (100 mg or placebo once a day for 7 days). Plasma and urinary concentrations of losartan and its active metabolite, E-3174, were determined. The mean Cmax and area under the curve (AUC) values increased in a dose-dependent manner. The terminal half-life of losartan ranged from 1.5 to 2.5 hours. Plasma concentration of E-3174 was higher than that of losartan at all dose levels. The Cmax and AUC values for E-3174 were approximately two and five to eight times higher than those for losartan, respectively. Furthermore, the half-life of E-3174 was two times that of losartan. After multiple dosing for 7 days, the pharmacokinetics of losartan or E-3174 did not change significantly between day 1 and day 7. Plasma renin activity and plasma concentration of A II increased at all dose levels. Plasma aldosterone levels were slightly reduced, but a similar decrease was also observed with placebo. The urinary excretion of uric acid within the first 4 hours after treatment was also increased in a dose-dependent manner, whereas the urinary excretion of creatinine remained unchanged. In other pharmacokinetic studies, it has been reported that bioavailability of losartan is about 33%, and its absorption is excellent. The metabolite is excreted via urine and the bile. Based on our observations, the half-life and plasma concentrations of E-3174 were greater than those of losartan. In conclusion, the long-lasting blocking effect of losartan on A II action can be attributed to the plasma levels of its active metabolite, E-3174.

Comparison of cholinergic vasodilator responses to acetylcholine and methacholine in the human forearm.

Abstract: In order to study the contribution of the nitric oxide (NO)-pathway to cholinergic vasodilatation in the resistance vessels of the human forearm, we infused acetylcholine (ACh; 0.1-1000 ng/kg/min) or methacholine (MCh; 0.1A100 ng/kg/min) in the presence of saline, the NO-scavener and guanylate cyclase inhibitor methylene blue (MB; 1000ng/kg/min), or the NO-synthase inhibitor NG-monomethyl-L-arginine (L-NMMA; 30 μg/kg/min) into the brachial artery of normotensive volunteers (n = 32), using venous occlusion plethysmography. We calculated the plasma concentrations of the infused compounds to obtain EC50-values (-log mol/1). ACh and MCh both caused concentration-dependent vasodilatation (ECso-values of 6.43 & 0.05 and 7.24 * 0.08, respectively). MB (13 μmol/1) did not change basal forearm blood flow (FBF) when administered alone, but it markedly potentiated the vasodilator response to ACh, shifting the concentration-response curve (CRC) leftwards by 1.5 log-step (p < 0.001). MB did not affect MCh-induced vaso...

Obesity and the sympathetic nervous system.

Abstract: Several epidemiological studies have shown that obesity represents an independent risk factor for development of cardiovascular diseases, including hypertension, myocardial ischaemia, and cardiac arrhythmias. Although the metabolic and the haemodynamic alterations occurring in the obese state have been well defined for several years, our knowledge on the sympathetic alterations occurring in this condition is more scarce and controversial. This paper reviews the evidence that human obesity is characterized by abnormalities in sympathetic cardiovascular control, in the light of the results of recent studies performed by employing a sensitive technique to assess sympathetic activity in humans, i.e. microneurography. Evidence is provided that sympathetic overactivity is a common hallmark of the obese state, even when blood pressure levels are within the normal range. It will also discuss the potential mechanisms responsible for this sympathetic activation, suggesting that overweight-related metabolic alterations, such as the insulin resistance state, and abnormalities in sympathetic cardiovascular control exerted by arterial baroreceptors may play a pathogenetic role. Finally, the effects of body weight reduction on the sympathetic overactivity which characterizes the obese state will also be examined.

Molecular mechanisms of insulin resistance in arterial hypertension.

Abstract: The associations between insulin resistance, hyperinsulinaemia, and hypertension are well recognized. Hyperinsulinaemia induces hypertension through increased renal tubular reabsorption of sodium and water, increased sympathetic nervous system activity, proliferation of vascular smooth muscle cells, and alterations of transmembrane cation transport. At physiological concentrations, insulin decreases urinary sodium excretion, an action mediated by binding to specific high-affinity receptors. Insulin resistance is present also in strains of rats with genetic hypertension (spontaneously hypertensive and Dahl salt-sensitive rats) that can be utilized as models to study the molecular mechanisms of this abnormality. In normal rats, the number and mRNA levels of insulin receptors in the kidney are inversely related with dietary sodium content, suggesting the existence of a feedback mechanism that limits insulin-induced sodium retention when extracellular fluid volume is expanded. We have investigated the relationships between dietary sodium intake and renal insulin receptors in spontaneously hypertensive rats and have found that in this strain the feedback mechanism is abolished. In addition, spontaneously hypertensive rats have decreased expression of the insulin receptor gene in the liver and decreased receptor autophosphorylation and phosphorylation of an endogenous substrate (IRS-1) in liver and muscle. These observations provide a potential explanation for the decreased sensitivity to insulin present in spontaneously hypertensive rats. In these rats, the loss of the capability to down-regulate insulin receptor in the kidney when extracellular fluid volume is expanded can lead to further sodium retention and might play a role in the development and maintenance of hypertension.

Insulin and the sympathetic nervous system in the pathophysiology of hypertension.

Abstract: The well-documented epidemiologic association of insulin levels and blood pressure have raised the possibility of a role for insulin in the pathogenesis of essential hypertension. The sympathetic nervous system (SNS) is a possible link in this relationship, since insulin is a critical mediator of dietary-induced changes in sympathetic activity. Insulin mediated glucose metabolism, in central neurons related anatomically to the ventromedial hypothalamus, mediates fasting-induced suppression, and overfeeding-induced stimulation of the SNS. The effect of insulin to stimulate the SNS is readily demonstrable in humans. The physiological role of insulin-mediated sympathetic stimulation is in the regulation of dietary thermogenesis, the linkage between dietary intake and metabolic rate. The association of hyperinsulinemia with hypertension in the obese led to the hypothesis that insulin-mediated sympathetic stimulation, recruited in the obese to increase metabolic rate and restore energy balance, had the unintended consequence of increasing blood pressure. Data developed in a population based cohort (The Normative Aging Study, NAS) support this hypothesis since: obesity was associated with evidence of increased SNS activity; there was a demonstrable relationship between glucose and insulin levels and SNS activity; and blood pressure was associated with both insulin and sympathetic activity, a relationship that was noted in the population as a whole after adjustment for body mass index and body fat distribution. Interruption of hyperinsulinemia in obese subjects, furthermore, decreased both plasma NE level and blood pressure. These data provide evidence that insulin-mediated sympathetic stimulation contributes to hypertension in the NAS population, and that the relationship occurs in both obese and non-obese subjects.

The Swedish Trial in old patients with hypertension-2 (STOP-hypertension-2): a progress report.

Abstract: Lindholm LH, Hansson L, Dahlof B, Ekbom T, Hedner T, de Faire U, Schersten B, Wester P-O. The Swedish trial in old patients with hypertension-2 (STOP-hypertension-2): a progress report.Objective: The Swedish Trial in Old Patients with Hypertension-2 (STOP-Hypertension-2) was designed by a project group of the Swedish Hypertension Society to test whether the “newer” treatment alternatives (ACE inhibitors and calcium antagonists) are as good as, better or less good than, the “older” ones (beta-blockers and diuretics) in terms of preventing cardiovascular morbidity and mortality in elderly hypertensives. The aim of the present paper is to report on the progress of the study.Design: Prospective, open trial with blinded end-point committee and centralized randomization (PROBE design). STOP-Hypertension-2 may be regarded as a scientific follow-up of the previously published Swedish Trial in Old Patients with Hypertension (STOP-Hypertension-I) (6) using the same study organization.Subjects: By the end of 1994 wh...

Angiotensin-converting enzyme-independent pathways of angiotensin II formation in human tissues and cardiovascular diseases.

Abstract: The tissue renin-angiotensin system plays an integral role in the homeostasis of blood pressure and in the pathogenesis of cardiovascular remodeling. These effects are primarily mediated through the paracrine and autocrine actions of locally produced angiotensin II (A II). It is generally accepted that the conversion of angiotension I to A II is mainly due to angiotensin-converting enzyme (ACE). However, there are several in vitro and in vivo reports of ACE-independent synthesis of A II in hypoxic and ischemic heart and blood vessels, which may also contribute to cardiovascular pathology. The differential cellular and regional expression of ACE and chymase in the human heart and blood vessels suggests distinct pathophysiologic roles for these two A II-forming enzymes. The study of different pathways involved in tissue A II formation, including that of ACE- and chymase-independent enzymes, will clarify their respective contribution to the pathophysiologic changes in cardiovascular diseases, and help in planning a more comprehensive clinical strategy. This report reviews the properties of human heart chymase, an A II-forming serine proteinase, and compares it with those of ACE.

Effects of increased arterial epinephrine on insulin, glucose and phosphate.

Abstract: Kjeldsen SE, Moan A, Petrin J, Weder AB, Julius S. Effects of increased arterial epinephrine on insulin, glucose and phosphate.The relationship between sympathetic nervous system activity and glucose and insulin metabolism is not fully understood. In the present study we therefore investigated the effect of raising arterial plasma epinephrine within the lower pathophysiolgical concentration range on insulin, glucose and phosphate in blood. Arterial plasma epinephrine was raised over 60 min by a stepwise increasing intravenous infusion in healthy men aged 20–40 years (n = 40). Compared with infusion of saline, epinephrine caused a small but significant rise in serum insulin of 10 ± 26 pmol/L (p = 0.016), more than 70% increase in serum glucose (p < 0.0001) and a decrease in serum phosphate (p < 0.0001). The changes in serum insulin during epinephrine infusion correlated negatively with the changes in arterial plasma epinephrine (r = -0.46, p = 0.003) and the changes in serum phosphate correlated negatively...

Brief report: acute renal failure after losartan treatment in a patient with bilateral renal artery stenosis.

Abstract: (1996). Case Report: Brief Report: Acute Renal Failure after Losartan Treatment in a Patient with Bilateral Renal Artery Stenosis. Blood Pressure: Vol. 5, No. 6, pp. 360-362.

Is hypertension changing ? Blood pressure development in cohorts of 50-year-old men between 1963 and 1993

Abstract: Ribacke M, Tibblin G, Rosengren A, Eriksson H. Is Hypertension changing? Blood pressure development in cohorts of 5-years-old men between 1963 and 1993.Objective: To study secular trends in the prevalence and treatment of hypertension in the general population, and the disease course. Design: Health examinations of cohorts of 50-year-old men in 1963, 1973, 1983 and 1993. Setting: The city of Goteborg, Sweden (about 400 000 inhabitants). Participants: Random population samples of 50-year-old men. Main outcome measure: Mean blood pressure (BP) levels in the populations and among treated hypertensives, proportions of hypertensives, and frequency of high BP values (≤ 160/and or 95, and ≤ 175/115 mmHg, respectively). Results: The mean population BP decreased from 138.4/89.0 mm to 128.7/84.4 mmHg during the 30-year period (p < 0.0001). Mean BP levels among treated hypertensives decreased from 170/113 to 142/94 mmHg (p < 0.001), and the proportion of men with high BP values diminished from 3.9 to 0.1%. Also BP l...

Clinical Implications of White Coat Hypertension

Abstract: Objective: To determine the clinical implications of mild white coat hypertension (WCH).Subjects and methods: We studied 102 subjects (54 men, 48 women). 51 of whom were normotensive and 51 slightly hypertensive. None had ever received antihypertensive therapy. An ambulatory blood pressure (ABP) record (Accutracker II), a 24-h electrocardiogram and an echocardiogram were obtained from each, and each was examined by funduscopy. WCH subjects were compared with sustained hypertension (SH) subjects and with normotensives.Results: Fifty-three percent of the hypertensives qualified as WCH. The ultrasonographic characteristics and the ABP variables of the WCH group differed significantly from those of normotensives, but not from those of the SH group. The prevalence of left ventricilar hypertrophy (LVH) in the SH group (62.5%) did not differ significantly from its prevalence in the WCH group (40.7%). but the prevalence among normotensives (17.6%) was significantly lower than in either of the other two groups. Th...

Marked hepatotoxicity associated with losartan treatment

Abstract: Losartan represent a novel approach in the treatment of hypertension. Clinical trials have reported a very low incidence of side effects. We describe two patients who developed increases in alanine/aspartate amino transferase of 8 and 15 times the upper normal limit, as well as thoracic pain, after a short time of treatment with losartan. The increase resolved after discontinuing losartan treatment.

Quality of life in hypertensive patients treated with either carvedilol or enalapril

Abstract: Ostergren J, Storstein L, Karlberg BE, Tibblin G for the study group. Quality of life in hypertensive patients treated with either carvedilol or enalapril.An important aspect of antihypertensive drug treatment is quality of life (QL) which should at least not be negatively affected. In this study, the QL during treatment with carvedilol (C), a beta-blocker with vasodilating properties due to alpha-1-receptor blockade, was compared to that of enalapril (E) in patients who had responded to the treatment.Patients und methods: Patients with mild to moderate hypertension (diastolic blood pressure 95–115 mmHg) were randomised to receive either E(n =119) of C(n = 129) in a double-blind multicenter study. The starting doses were 12.5 (C) and 10 (E) mg with doubling of the dose if necessary at 3-week intervals. If insufficient blood pressure (BP) control was found at 50 mg C or 40 mg E, 12.5 mg of hydrochlorothiazide was added. After having reached the goal BP the patients entered a 5-months maintenance period. Ge...

The crosstalk between insulin and the sympathetic nervous system: possible implications in the pathogenesis of essential hypertension.

Abstract: Patients with non-insulin dependent diabetes mellitus and obesity show an elevated risk for development of arterial hypertension, while many non-obese, non-diabetic patients with essential hypertension display resistance to insulin-induced glucose disposal, accompanied by hyperinsulinaemia. This close association has lead some investigators to postulate that insulin resistance could be implicated in the pathogenesis of essential hypertension. Among the various factors considered as potential links between insulin resistance and high blood pressure, the sympathetic nervous system can be considered a prime candidate. In particular, our recent data in hypertensive patients have documented that the muscle sympathetic response evoked by insulin is about threefold greater than that observed in normal subjects. Such finding is well in agreement with previous observations in hypertensives obtained with experimental maneuvers and extends them by showing an abnormal sympathetic response to a physiological stimulus like insulin, so important in every day life. Recent data both from our and other laboratories have clearly established that an acute activation of sympathetic nervous system is able to antagonize insulin-mediated glucose uptake in the skeletal muscle, making very real the possibility that a primary defect in insulin sensitivity in hypertension may be further aggravated by the greater sympathetic response evoked by episodic stimuli, such as postprandial hyperinsulinaemia. However, while insulin evokes an increase in sympathetic nervous activity, at same time it is able to blunt the vasoconstrictive effects caused by the reflex sympathetic activation. Such vascular modulating effect of insulin is lost in essential hypertension, indicating that the resistance to insulin effect in this disease is not only present in skeletal muscle metabolism but it is also evident at the vascular level.

Global efficacy and tolerability of losartan, an angiotensin II subtype 1-receptor antagonist, in the treatment of hypertension.

Abstract: Losartan is the first drug of a new therapeutic class, the angiotensin II (A II)-receptor antagonists, to be clinically studied and become available for the management of hypertension. Clinical experience with losartan from worldwide, double-blind, controlled studies has been obtained in more than 2900 hypertensive patients treated with losartan alone or in combination with hydrochlorothiazide, with 1700 patients receiving treatment for more than a year. The efficacy of losartan was evaluated in the young and old, in different degrees of hypertension, in blacks and nonblacks, and in patients with renal impairment. Tolerability parameters were assessed by subgroup as well. In dose-ranging studies, 50 mg once daily has generally been shown to produce near maximum effects and a dose of 100 mg does not produce additional effects. The efficacy of losartan (50 to 100 mg once daily) has been compared to atenolol (50 to 100 mg once daily), felodipine ER (5 to 10 mg once daily), and enalapril (20 mg once daily). The blood pressure-lowering effect of losartan was comparable to felodipine, enalapril, and atenolol. The efficacy of losartan was demonstrated using ambulatory blood pressure monitoring, which showed that losartan 50 mg once daily produced gradual reduction in blood pressure, providing 24-h control without affecting the body's circadian rhythm. In subgroups of study populations, no differences in efficacy were noted with respect to age, gender and the severity of hypertension. No initial dosage adjustment is necessary in the elderly and patients with renal impairment (even those on dialysis). Among blacks, the mean response of losartan was lower, which is not surprising given the lesser activation of the renin-angiotensin system in this population. A subgroup safety and tolerability analysis confirmed that there were no important differences in adverse events when assessed by age, race, or gender. The data obtained from controlled clinical trials conducted with losartan, the first A II-receptor antagonist, has shown that a single daily 50-mg dose provides adequate 24-h control of blood pressure in most patients with comparable efficacy to other classes and is well tolerated.

Hypertension in pregnancy and size at birth.

Abstract: Low birth weight and high placental weight are associated with increased cardiovascular morbidity and mortality. Children born after hypertensive pregnancies have higher blood pressure than children born after normotensive pregnancies. Hypertension in pregnancy is considered a major risk factor for intrauterine growth retardation. The present study describes size at birth and perinatal characteristics in children born after hypertensive pregnancies. During five consecutive years 17,000 deliveries took place in the well defined geographic area of eastern Goteborg. Hypertension in pregnancy complicated 261 pregnancies. For comparison 260 normotensive pregnancies, matched for maternal age and time of delivery, were used. Standard deviation score for birth weight and length were calculated according to reference standards for birth weight (BWSDS) and length (BLSDS) based on all Swedish births 1977-1981 (n = 475,588). Children born after hypertensive pregnancies had lower birth weight, were shorter and had a shorter gestational period as compared with children born after normotensive pregnancies. Head circumference and placental weight did not differ and there were no significant differences in BWSDS. It is concluded that hypertensive pregnancies are characterized by lower birth weight and shorter gestational period. However, intrauterine growth retardation is not a general characteristic of hypertension in pregnancy.

Considerations on current and future trials in hypertension.

Abstract: Conclusive evidence from large-scale epidemiological studies has shown that hypertension is a major risk factor for cardiovascular disease. Large-scale intervention trials have indicated that, by reducing elevated blood pressure values with antihypertensive treatment, the risk can be decreased. Despite the large body of evidence on the protective effects of the blood pressure reduction, several questions concerning the benefit of antihypertensive treatment remain unanswered. This paper briefly reviews the information provided by clinical trials on antihypertensive treatment. It also critically examines the questions that have remained partially or totally unanswered and the trials that are currently addressing them. Focus is directed on the Insight Study which addresses the benefit of antihypertensive treatment in hypertensive subjects with additional cardiovascular risk factors.

Diagnosing Renal Artery Stenosis: A Comparison Between Conventional Renography, Captopril Renography and Ultrasound Doppler in a Large Consecutive Series of Patients with Arterial Hypertension

Abstract: The purpose of the study was to compare the positive and negative predictive values of conventional renography (Reno-A), captopril renography (Reno-B) and ultrasound Doppler (UD) with regard to the diagnosis renal artery stenosis. These three tests, and in addition a renal angiography, were performed in consecutively admitted patients with arterial hypertension, owing to either suspicion of renovascular hypertension or refractoriness to treatment. Patients with occlusion of a renal artery or a serum creatinine level higher than 300 μmol/1, or a previous investigation for renovascular hypertension at another hospital, were excluded from the analysis. The European Multicenter Study (EMS) criteria and local criteria for abnormal renography were compared. Of 131 patients, 28 had a renal artery stenosis (RAS) exceeding 50% reduction in diameter of the artery and 19 exceeding 70%. Using the EMS criteria for renography the predictive values of a negative test for a RAS more than 50% were 0.88 for Reno-A, 0.90 fo...

Concomitant risk factors in hypertensives: a survey of risk factors for cardiovascular disease amongst hypertensives in English general practices.

Abstract: Aims: To determine the prevalence of cardiovascular risk factors among hypertensives in a cross-sectional survey of hypertensives from 13 general practices in England.Conclusion: It is important to consider other cardiovascular risk factors in hypertensives because they are very common and interact with blood pressure (BP) to determine levels of risk. The high proportion of inadequately controlled hypertensives demands a more effective management strategy.Findings: Of 1,948 European hypertensives (systolic blood pressure 150 mmHg and/or diastolic blood pressure >90mmHg and/or on treatment for hypertension), 40 to 69 years of age, 53.3% on treatment had controlled blood pressures (systolic blood pressure < 160 mmHg and diastolic blood pressure <95 mmHg). Electrocardiographic abnormalities and other cardiovascular risk factors were common among these hypertensives, with dyslipidaemia, past or current smoking and lack of physical exercise being present in the majority of those studied. All risk factors excep...

The diversified pharmacology of angiotensin II-receptor blockade.

Abstract: The discovery of orally active nonpeptide angiotensin II (A II)-receptor antagonists has initiated a growing understanding of the physiologic and pathophysiologic roles of A II. Losartan is the first of the new class of antagonists that block all the well-known effects of A II, including vasoconstriction, aldosterone release, renin release (negative feedback), and the stimulation of thirst. A II-receptor subtypes have been described, with losartan antagonism defining the AT1 subtype and with PD123319 antagonism defining the AT2 subtype. The AT1 receptor is G-protein-coupled, involving PLC, PLA2, PLD, or adenylate cyclase and the release of intracellular calcium. The receptor-response coupling of the AT2 site remains elusive but may involve protein tyrosine phosphatase and subserve an antiproliferative role. Losartan as the prototype of an AT1-selective antagonist: i) inhibits A II binding, ii) antagonizes effects of A II in vivo and in vitro, and iii) lowers blood pressure in models of A II-dependent hypertension A II stimulates growth in vitro (DNA and protein synthesis) and in vivo (cardiac and vascular hypertrophy), and these effects are blocked by losartan. Losartan, like angiotensin-converting enzyme inhibitors, has significant renal, cardiac, and cerebral protective effects in models of renal failure, cardiac failure, and stroke, confirming the pathologic role of A II in these models. The pioneering studies in experimental animals are being confirmed by a growing number of other AT1-selective blockers and provide the basis of use of losartan for hypertension and its clinical trial in other disease states.

Salt sensitivity and insulin resistance: Is there a link?

Abstract: Salt sensitivity is not only found in patients with essential hypertension but also in normotensive individuals. These salt-sensitive normotensives are believed to be genetically predisposed to the development of hypertension. In this paper we present data from our studies in such normotensive salt-sensitive individuals, thereby focusing on the relationship between salt sensitivity and familial history of hypertension and on insulin sensitivity. Salt-sensitivity was associated with a positive familial history of hypertension, a finding that supports the hypothesis that salt sensitivity in normotensive individuals points to a genetic predisposition for the development of hypertension. Also, salt-sensitive subjects displayed a hyperinsulinaemic response to an oral glucose load and a decreased insulin-mediated glucose disposal, as assessed by the insulin suppression test. The latter finding implies that insulin resistance is present in otherwise healthy, hypertension-prone individuals before overt hypertension develops. Assuming that there is a pathophysiological relationship between insulin resistance and salt sensitivity, our findings suggest that early recognition of insulin resistance and the implementation of measures aimed at improving insulin sensitivity could contribute to the prevention of cardiovascular disease in these individuals.

Salt Sensitivity in Hypertensive Type-1 Diabetes Mellitus

Abstract: Gerdts E, Svarstad E, Myking OL, Lund-Johansen P, and Omvik P. Salt sensitivity in hypertensive type-I diabetes mellitus.As sodium retention has been proposed as a causal factor in the development of hypertension in diabetic patients, a high incidence of salt sensitivity has been suggested. To evaluate the influence of dietary sodium intake on blood pressure, casual and 24-h blood pressure was measured in 30 hypertensive type-I diabetic patients aged 24-67 (mean 46) years while they were on habitual diet, after 6 days of low-sodium diet (50 mmol/day), and after 6 days of high-sodium diet (250mmol/day). Nine patients (30%) who increased their 24-h mean blood pressure by more than 10% when going from low- to high-sodium intake were classified as salt sensitive; the others as salt resistant. The salt sensitive group had a significantly lower urinary excretion of dopamine at baseline, and a higher diuresis and a more pronounced decrease in 24-h blood pressure during salt depletion (all p < 0.01). Low-sodium d...

Prediction models for insulin resistance.

Abstract: A prediction model for estimating insulin resistance in hypertensive patients is presented. Body-mass index, serum triglyceride concentrations and liver enzyme activity in plasma correlate to insulin resistance determined with the euglycaemic, hyperinsulinaemic clamp technique. Prediction models using body-mass index and either triglycerides or serum alanine-amino transferase were equally good in predicting insulin resistance and gave results that were; is reliable as those obtained in a model using fasting-insulin concentrations. The hyperinsulinaemic clamp had a reproducibility error of 14%, and body-mass index and serum triglycerides had a multiple correlation of 0.57 to the insulin-sensitivity results. The model predicts insulin resistance with acceptable statistical power, whereas the power to predict high values of insulin sensitivity is less good.

Interrelationships between salt and fish oil in stroke-prone spontaneously hypertensive rat.

Abstract: Vaskonen T, Laakso J, Mervaala E, Sievi E, Karppanen H. Interrelationships between salt and fish oil in stroke-prone spontaneously hypertensive rat.The cardiovascular effects of a partially purifie...

The role of the renin-angiotensin system in the pathophysiology of cardiac remodeling.

Abstract: Cardiac hypertrophy of diverse etiologies is associated with two remodeling events: an increase in cardiac muscle mass, and the abnormal accumulation of fibrillar collagen, which results in increased myocardial stiffness and eventual ventricular dysfunction. Clinical and animal studies have implicated angiotensin II (A II) as a growth promoter of both cardiac myocytes and fibroblasts during the cardiac remodeling that occurs with hypertension and myocardial infarction. The growth-promoting effects of A II occur, in part, independent of effects on hemodynamic load. Tissue culture studies have shown that cardiac myocytes and fibroblasts are targets for the actions of A II. In these cells. A II activates phospholipases C, D, and A2, leading in turn to the activation of multiple, conventional second-messenger pathways. By an undefined process. A II also increases the tyrosine phosphorylation of cytosolic proteins, and activates the STAT family of transcription factors, which may mediate an inflammatory or stress response. A II has been shown to affect gene expression of cultured cardiac myocytes and fibroblasts, induce either cellular hyperplasia or hypertrophy, and increase expression of other growth factors. Cardiac fibroblasts have been shown to respond to A II with increased expression of integrins and the extracellular matrix proteins, collagen and fibronectin. Recently, stretch of cardiac myocytes was shown to induce hypertrophy, through an autocrine release of A II. All of the aforementioned actions of A II are mediated by the AT1 receptor.