Biomedical subjects

P Weidmann

Publications and source records attributed to P Weidmann.

At least 73 records · Page 4Linked to original sources

PubMed1991

Antihypertensive agents, serum lipoproteins and glucose metabolism.

Effective blood pressure control with traditional high-dose diuretic therapy has led to a distinct decrease in cerebrovascular morbidity and mortality, but failed to achieve a satisfactory reduction of coronary complications and sudden death. The same applies also for beta blockers, although they have been shown to be effective in secondary prevention of myocardial infarction. It is suspected that conventional antihypertensive treatment has an unfavorable effect on coronary risk factors other than hypertension. For instance, thiazide-type diuretics can impair glucose tolerance and increase the potentially atherogenic serum low-density lipoprotein (LDL) cholesterol fraction and triglycerides. Beta blockers without partial intrinsic sympathomimetic activity increase serum triglycerides and tend to lower the potentially antiatherogenic high-density lipoprotein (HDL) cholesterol. Certain beta blockers may also impair glucose tolerance, particularly when they are combined with diuretics. Calcium channel blockers, angiotensin converting-enzyme inhibitors and alpha 1-receptor blockers do not adversely affect lipoprotein or carbohydrate profiles. The latter two drug classes may even increase insulin sensitivity, and alpha 1 blockers may also slightly improve lipid metabolism. The prognostic relevance of drug-induced dyslipidemia and/or glucose intolerance awaits further clarification. In the meantime, it is of clinical interest that several of the generally available antihypertensive drugs seem to be metabolically neutral or sometimes perhaps even potentially beneficial with regard to the lipoprotein and carbohydrate metabolism.

Antihypertensive Agents↗

PubMed1991

[The treatment of orthostatic hypotension with metoclopramide].

The dopamine receptor antagonist metoclopramide (paspertin, primpéran, gastrosil, meclopran, gastro-timelets), used as monotherapy or in combination with an inhibitor of the cyclooxygenase enzyme, affords good results in orthostatic hypotension due to insufficiency of the sympathetic nervous system. The mechanism of action in these cases is unclear but is assumed to be elevation of vascular tone in the splanchnic vessels. A case is discussed which documents the effectiveness of metoclopramide therapy in orthostatic hypotension, even in absence of signs of autonomic dysfunction.

Aged↗

PubMed1991

Unaltered insulin sensitivity during calcium channel blockade with amlodipine.

The sensitivity of peripheral tissues to insulin is of pathophysiological, therapeutic and possibly also of prognostic relevance. Calcium channel blockers are widely used in the treatment of cardiovascular disorders that are commonly associated with decreased insulin sensitivity (SI). To evaluate the effects of calcium channel blokkade on SI, glucose homoeostasis and lipid profiles, studies were made of SI (determined by the Minimal Model Method of Bergman), basal glucose and insulin levels, serum total triglyceride (Tg) and lipoprotein cholesterol (C) fractions and certain other variables in 38 healthy young men (24 y) during placebo and after 3 weeks of calcium channel blockade with amlodipine 5 mg once daily. Measurements were made after 3 days on a standard diet (2200 kcal.day-1, 45% carbohydrates, 40% fat and 15% proteins) and after an overnight fast. Compared to placebo, amlodipine decreased supine systolic blood pressure (P less than 0.01). Heart rate, body weight and 24 h urinary sodium excretion were unaltered, and so were fasting plasma glucose (placebo vs amlodipine: 4.86 vs 4.83 mmol.l-1, respectively) and insulin levels (7.7 vs 7.9 microU.ml-1), SI (10.5 vs 9.6.10(-4) x min-1 pro microU.ml-1), serum total Tg, C and lipoprotein C fractions. The findings demonstrate unchanged insulin sensitivity and secretion, as well as lipoprotein regulation, during maintenance administration of 5 mg amlodipine daily to healthy young men.

Adult↗

PubMed1991

Reproducibility of insulin sensitivity measured by the minimal model method.

Insulin resistance is a critical component underlying the altered glucose homeostasis in a variety of metabolic and non-metabolic disorders. Aging, body fat distribution, obesity, diabetes mellitus or hypertension are well recognized conditions associated with an impaired tissue sensitivity to insulin action. Apart from such constant factors, insulin sensitivity can be acutely modified by independent variables such as physical exercise, dietary factors, alcohol intake or harmless drugs. To evaluate the day-to-day intra-individual variation in insulin sensitivity, glucose homeostasis and lipid profiles, we investigated the insulin sensitivity index (S1) (determined by the minimal model method of Bergman), basal and post-glucose-load insulin and glucose levels, serum total triglyceride and lipoprotein cholesterol fractions in 15 healthy young men (24 +/- 1 year, mean +/- SEM), on two different occasions at an interval of 3 weeks (days 1 and 21), after 3 days of a standard dietary regimen and after an overnight fast. Blood pressure, heart rate, body weight and 24 h urinary sodium excretion were almost identical in the two phases. S1(day 1) varied from 4.2 to 15.8 x 10(-4).min-1 pro microU/ml (mean: 10.2 +/- 0.9) and correlated with S1(day 21) (11.2 +/- 1.2 x 10(-4).min-1 pro microU/ml, r = 0.78, p less than 0.0007). The slope of the relationship did not differ from 1 (1.01, p greater than 0.90), the intercept was close to the origin (0.8, p greater than 0.73) and the coefficient of variation was 14.4%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1991

Altered insulin sensitivity, hyperinsulinemia, and dyslipidemia in individuals with a hypertensive parent.

PURPOSE: Essential hypertension is, in some patients, complicated by impairment of insulin-mediated glucose disposal and hyperinsulinemia. Whether this metabolic disturbance is a consequence of the hypertensive process or whether it may precede, and thus possibly promote, the development of hypertension has been unknown. SUBJECTS AND METHODS: Searching for hereditary or familial defects in hypertension-prone humans, we prospectively investigated insulin sensitivity, plasma insulin and glucose, and serum lipoproteins in normotensive offspring of essential hypertensive as compared with age- and body habitus-matched offspring of normotensive families. RESULTS: Compared with 78 control subjects, 70 offspring of essential hypertensive parents had similar age (mean +/- SEM: 24 +/- 1 versus 24 +/- 1 years, respectively) and body mass index (22.3 +/- 0.2 versus 22.4 +/- 0.2 kg/m2), a blood pressure of 127/77 +/- 1/1 versus 123/76 +/- 1/1 mm Hg (p less than 0.05 for systolic), and significantly elevated (p less than 0.01 to 0.001) fasting plasma insulin levels (9.9 +/- 0.3 versus 8.6 +/- 0.3 microU/mL), serum total triglycerides (1.03 +/- 0.06 versus 0.83 +/- 0.03 mmol/L), total cholesterol (4.37 +/- 0.08 versus 3.93 +/- 0.07 mmol/L), low-density lipoprotein cholesterol (2.45 +/- 0.08 versus 2.14 +/- 0.07 mmol/L), and total/high-density lipoprotein cholesterol ratio (4.3 +/- 0.1 versus 3.7 +/- 0.1). Insulin sensitivity was lower (9.4 +/- 0.7 versus 13.2 +/- 1.1 x 10(-4) x minute-1/microU/mL, p less than 0.001), while post-glucose-load plasma insulin levels were higher (p less than 0.05) in the 41 offspring of essential hypertensive parents than in the 38 offspring of normotensive parents so investigated. CONCLUSION: These findings demonstrate that young normotensive humans in apparently excellent health but with one essential hypertensive parent tend to have an impairment of insulin-mediated glucose disposal, hyperinsulinemia, and dyslipidemia. It follows that a familial trait for essential hypertension seems to coexist commonly with defects in carbohydrate and lipoprotein metabolism that can be detected before or at least at a very early stage of the development of high blood pressure as judged by resting blood pressure measurements.

Adolescent↗

PubMed1991

Cardiovascular pressor reactivity after chronic converting enzyme inhibition.

In addition to inhibiting the formation of angiotensin II, chronic converting enzyme inhibition may affect other blood pressure modulating factors. The influence of an 8 week treatment phase with cilazapril on the activity of the renin-angiotensin-aldosterone and sympathetic nervous systems, the pressor reactivity to infused angiotensin II or norepinephrine, the chronotropic response to isoproterenol, and body sodium and plasma atrial natriuretic peptide concentrations was assessed in 11 normal subjects and 12 patients with essential hypertension. As compared to a 4 week placebo phase, cilazapril decreased arterial pressure in both study groups (from 124/83 +/- 9/6 to 114/77 +/- 9/5 mm Hg and from 143/102 +/- 13/7 to 137/96 +/- 10/10 mm Hg; P less than .025); exchangeable sodium (-158 mmol and, respectively, -104 mmol) and upright plasma aldosterone (-24% and -15%) also tended to fall. Heart rate, the chronotropic response to posture or isoproterenol, plasma norepinephrine levels, the concentration/pressor response curve to norepinephrine, plasma atrial natriuretic peptide concentration, plasma angiotensin II and the responses of blood pressure or plasma aldosterone to angiotensin II were unchanged after 8 weeks of cilazapril. Plasma renin activity increased (+175% to +650%). These findings indicate that the blood pressure lowering effect of cilazapril in the stable phase of pharmacological intervention is not associated with modifications of sympathetic-dependent pressor reactivity or beta-adrenergic sensitivity. Plasma angiotensin II concentration and angiotensin II-dependent pathways including the pressor and aldosterone responsiveness to angiotensin II are also unchanged.

Adolescent↗

PubMed1991

Atrial natriuretic factor after cardiac surgery with cardiopulmonary bypass in children.

OBJECTIVE: To determine circulating atrial natriuretic factor (ANF) concentrations in the postoperative state and to define potential hemodynamic determinants of regional plasma ANF concentrations. DESIGN: Cohort study. SETTING: Pediatric ICU in a university hospital. PATIENTS: Twenty-two children, mean age 4.2 yrs (range 0.9 to 13.5), were studied 18 hrs after corrective surgery on cardiopulmonary bypass. The underlying cardiac malformations were ventricular septum defect (n = 5), transposition of great arteries (n = 5), tetralogy of Fallot (n = 4), pulmonary stenosis (n = 3), and miscellaneous (n = 5). INTERVENTIONS: In addition to the commonly monitored variables in postoperative cardiac patients, blood volume was estimated by the 125I albumin method, and plasma samples for radioimmunoassay determination of ANF concentrations were taken simultaneously from indwelling catheters. MEASUREMENTS AND MAIN RESULTS: Compared with normal age-matched values, plasma ANF concentrations were increased in all patients, with values tending to be highest in the left atrium, followed by systemic artery, superior vena cava, and pulmonary artery (345 +/- 158, 333 +/- 169, 311 +/- 154, and 272 +/- 160 pg/mL, respectively [mean +/- SD; NS]). Simple regression analysis demonstrated a moderate correlation between blood volume and the concentration of ANF in the superior vena cava (p less than .05). Stepwise multivariate analysis showed no significant independent predictor of plasma ANF concentrations. CONCLUSIONS: Plasma ANF concentrations are increased after open-heart surgery in children, with moderate direct correlation to blood volume. The wide scatter of increased hormone concentrations may be explained by the many factors known to influence circulating ANF concentrations, such as age, underlying disease, cardiovascular state, and drugs.

Adolescent↗

PubMed1991

Modulation of noradrenergic but not angiotensinergic blood pressure control by beta-blockade with carteolol.

Various beta-blockers possessing similar antihypertensive potency have been found to differ widely with regard to their influence on blood pressure-regulating factors such as cardiac output and plasma levels of renin or norepinephrine. Recently, beta-blocker-induced stimulation of circulating atrial natriuretic factor (ANF) was reported. Blood pressure is determined not only by levels of vasoconstrictive factors but also by tissue reactivity. To investigate these aspects, we assessed the cardiovascular responsiveness to norepinephrine and angiotensin II, plasma levels of catecholamines, angiotensin II, ANF and aldosterone and the body sodium-blood volume state of 15 patients with essential hypertension (mean age +/- s.e.m., 42 +/- 3 years) and 12 normal control subjects (41 +/- 5 years), first on placebo and then after 4 weeks of intervention with carteolol, a non-selective beta-adrenergic antagonist with intrinsic sympathomimetic activity. Compared with placebo, carteolol decreased resting plasma norepinephrine in both groups while plasma norepinephrine-blood pressure response curves were shifted to the left, their slopes increased and norepinephrine pressor doses decreased (P less than 0.05 to less than 0.001). Chronotropic responses to isoproterenol were abolished but negative chronotropic responses to a norepinephrine-induced 20 mmHg rise in diastolic blood pressure were unaltered. Plasma norepinephrine clearance in the supine position was slightly decreased in hypertensive and unchanged in normal subjects. Supine and upright blood pressure was lowered (P less than 0.05 to 0.001) in the hypertensive while upright systolic blood pressure only decreased in the normal group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1991

Postsynaptic alpha 1-blockade with terazosin does not modify insulin sensitivity in nonobese normotensive subjects.

Plasma insulin levels and the sensitivity of peripheral tissue to insulin (SI) have pathophysiological, therapeutic, and possibly also prognostic relevance. To investigate the effects of short-term selective alpha 1-adrenergic receptor blockade in nonobese normotensive humans on glucose and lipoprotein homeostasis, we assessed SI (determined by the minimal model method of Bergman), before and after glucose load plasma, glucose, and insulin levels, serum total triglycerides and lipoprotein cholesterol fractions, and some other variables in 20 healthy young men (26 +/- 1 years old, mean +/- SEM) during placebo and after 5 weeks of terazosin administration at a dose up to 10 mg once daily. Measurements were made after 3 days of standard diet (2,500 kcal/day, 45% carbohydrates, 40% fat, and 15% proteins) and after an overnight fast. Compared to placebo, terazosin decreased the upright systolic blood pressure (placebo vs. terazosin: 125 +/- 2 vs. 117 +/- 2 mm Hg, p less than 0.05) and increased supine (63 +/- 2 vs. 70 +/- 1 beats/min, p less than 0.05) and upright (77 +/- 2 vs. 88 +/- 2 beats/min, p less than 0.01) heart rates, while the body weight was unaltered. Terazosin did not significantly modify fasting plasma glucose (5.08 +/- 0.09 vs. 5.23 +/- 0.08 mmol/L, respectively), or insulin (8.9 +/- 0.5 vs. 8.6 +/- 0.6 microU/ml), SI (14.3 +/- 1.8 vs 11.8 +/- 1.5 x 10(-4)/min/microU/ml), the areas under the insulin or glucose curves, serum total triglycerides, and cholesterol or lipoprotein cholesterol fractions.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Antagonists↗

PubMed1991

Developing essential hypertension: a syndrome involving ANF deficiency?

The pathogenesis of essential hypertension may possibly involve a deficiency in, or a decreased response to, endogenous vasodilator and natriuretic factor(s). Searching for hereditary or familial defects, it is plausible to evaluate blood pressure (BP) regulating factors in (yet) normotensive offspring of hypertensive parents (OHyp), some of whom are in fact in a stage of prehypertension. Studies by our group demonstrated that compared with healthy offspring of normotensive parents, OHyp have plasma atrial natriuretic (ANF) factor levels that are unaltered on a low salt intake but often fail to increase normally in response to a high salt intake. Plasma levels of cyclic GMP, the presumed second messenger of ANF, also may tend to be decreased in certain OHyp. On the other hand, renal excretory responses of cyclic GMP and electrolytes to ANF infused in "physiological" dose were unchanged in some OHyp tested so far. In borderline to moderate, uncomplicated essential hypertension, plasma ANF levels are often "normal." This may be inappropriately low relative to the existing BP, although the relationship of circulating ANF to atrial pressures in essential hypertension remains to be clarified. A conversion to higher plasma ANF values may occur with cardiac complications such as left ventricular hypertrophy, enlargement, dysfunction, or overt heart failure. Acute or short-term elevation of circulating ANF within the physiological and pathophysiological range by ANF infusion produces an exaggerated natriuresis and lowers BP in essential hypertensive patients. We postulate a syndrome of ANF deficiency, characterized by an impaired response of circulating ANF to high salt intake and by low cyclic GMP levels in certain yet normotensive offspring of essential hypertensive parents and by inappropriately "normal" plasma ANF in some patients with uncomplicated essential hypertension. At the stage of prehypertension, a disturbance in the ANF - cyclic GMP pathway may be expressed primarily at the circulatory rather than at the renal level. Hypertension-prone humans also tend to have an exaggerated vascular reactivity to norepinephrine. Whether the two disturbances may be interrelated is presently unknown. Both defects may potentially predispose to the development of essential hypertension. Relative ANF deficiency, an enhanced natriuretic response to ANF, and a sustained antihypertensive effect of infused ANF may represent a rational basis for treatment of essential hypertension with agents that activate the ANF system.

Animals↗

PubMed1991

Enhanced exercise-induced rise of aldosterone and vasopressin preceding mountain sickness.

A possible contribution of exercise to the fluid retention associated with acute mountain sickness (AMS) was investigated in 17 mountaineers who underwent an exercise test for 30 min on a bicycle ergometer with a constant work load of 148 +/- 9 (SE) W at low altitude (LA) and with 103 +/- 6 W 4-7 h after arrival at 4,559 m or high altitude (HA). Mean heart rates during exercise at both altitudes and during active ascent to HA were similar. Exercise-induced changes at LA did not differ significantly between the eight subjects who stayed well and the nine subjects who developed AMS during a 3-day sojourn at 4,559 m. At HA, O2 saturation before (71 +/- 2 vs. 83 +/- 2%, P less than 0.01) and during exercise (67 +/- 2 vs. 72 +/- 1%, P less than 0.025) was lower and exercise-induced increase of plasma aldosterone (617 +/- 116 vs. 233 +/- 42 pmol/l, P less than 0.025) and plasma antidiuretic hormone (23.8 +/- 14.4 vs. 3.4 +/- 1.8 pmol/l, P less than 0.05) was greater in the AMS group, whereas exercise-induced rise of plasma atrial natriuretic factor and changes of hematocrit, potassium, and osmolality in plasma were similar in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Acclimatization↗

PubMed1991

Antihypertensive therapy with Ca2+. Antagonist verapamil and/or ACE inhibitor enalapril in NIDDM patients.

OBJECTIVE: To assess the efficacy and tolerance of a diuretic-free antihypertensive therapy with a Ca2+ antagonist and an angiotensin-converting enzyme (ACE) inhibitor in patients with non-insulin-dependent diabetes mellitus (NIDDM). RESEARCH DESIGN AND METHODS: After a 2-wk washout and a 4-wk placebo phase, 47 hypertensive patients with NIDDM randomly received verapamil or enalapril alone and, if blood pressure remained elevated, both agents combined over 30 wk. RESULTS: Verapamil or enalapril alone normalized blood pressure to less than 90 mmHg diastolic in 30 patients; verapamil decreased mean +/- SE blood pressure from 159/98 +/- 3/1 to 146/87 +/- 3/2 mmHg (n = 18, P less than 0.001) and enalapril from 166/99 +/- 5/2 to 146/86 +/- 3/1 mmHg (n = 12, P less than 0.001). In 17 patients who were still hypertensive after 10 wk of monotherapy, combination of both drugs decreased blood pressure from 170/104 +/- 4/2 to 152/90 +/- 4/2 mmHg (P less than 0.001). Fasting plasma glucose, glycosylated hemoglobin, serum fructosamine, total lipids, high-density and low-density lipoprotein cholesterol, apolipoproteins A-I and B, creatinine, and urinary albumin-creatinine ratio were not significantly modified. CONCLUSIONS: In hypertensive patients with NIDDM, a diuretic-free therapy based on the Ca2+ antagonist verapamil and/or the ACE inhibitor enalapril can effectively decrease blood pressure without adversely affecting carbohydrate and lipid metabolism.

Blood Glucose↗

PubMed1991

Central role of sodium in hypertension in diabetic subjects.

The common association between diabetes mellitus and hypertension may be promoted by several mechanisms. Patients with insulin-dependent (type I) diabetes and prone to develop nephropathy often have a familial predisposition for essential hypertension, whereas normotensive healthy offspring of nondiabetic essential hypertensive parents tend to have a reduced insulin sensitivity and increased plasma insulin levels. Na+ retention occurs as a characteristic alteration in type I or non-insulin-dependent (type II) diabetes; exchangeable body Na+ (Naex) is increased by 10% on average. This abnormality develops in the uncomplicated stage of diabetes and differentiates diabetic from nondiabetic essential hypertensive subjects. Possible Na(+)- retaining mechanisms include increased glomerular filtration of glucose leading to enhanced proximal tubular Na(+)-glucose cotransport, hyperinsulinemia (which activates several tubular Na+ transporters), an extravascular shift of fluid with Na+, and, once it occurs, renal failure. The pathogenetic role of Na+ retention in diabetes-associated hypertension is supported by positive correlations between systolic or mean blood pressure and Naex and by normalization of blood pressure after removal of excess Na+ by diuretic treatment in hypertensive diabetic subjects. The latter may also have an enhanced sensitivity of blood pressure to Na+. Plasma levels of active renin, angiotensin II, aldosterone, and catecholamines are usually normal or low in metabolically stable type I or type II diabetes. However, an exaggerated vascular reactivity to norepinephrine and angiotensin II commonly occurs already at uncomplicated stages of type I or type II diabetes. This may be a manifestation of functional (i.e., intracellular electrolytes) and/or morphological (proliferation, narrowing, and stiffening) vasculopathy. Diabetes-associated Na+ retention, vasculopathy, and a presumably inherited predisposition for both diabetes and essential hypertension may represent important complementary factors favoring the frequent occurrence of hypertension in the diabetic population.

Diabetes Mellitus, Type 1↗

PubMed1991

Effects of slow ascent to 4559 M on fluid homeostasis.

Since acute mountain sickness (AMS) is associated with rapid ascent and with fluid retention, we assessed clinical status and fluid homeostasis in men slowly ascending on foot over 3 d to 4559 m and remaining at this altitude 5 d. We studied 15 male mountaineers, 6 of whom had previously had repeated, severe AMS or high altitude pulmonary edema (HAPE), at 1170 m, 3611 m, and 4559 m. We found that four of the six subjects with previous AMS or HAPE compared with none of nine with no such history, developed these conditions. Those who remained well had a diuresis that could not be overcome by increasing fluid intake and no change in renin activity, plasma aldosterone, or atrial natriuretic peptide (ANP). Those who became ill showed considerable weight gain independent of fluid intake, and a great increase in ANP which correlated with measurements of right atrial cross section. We conclude that mountaineers who have previously experienced repeated AMS or HAPE get fluid retention despite slow ascent and that this is associated with widening of the atrium and an increase in ANP.

Adult↗

PubMed1990

Association between sympathetic activity and the atherogenic serum cholesterol fraction.

A possible modulating influence of noradrenergic activity on serum lipoproteins was assessed under placebo conditions and following 4 weeks of sympathetic neurone blockade with debrisoquine in 9 normal subjects, 11 patients with mild essential hypertension, 9 normotensive, and 9 hypertensive hemodialysis patients. Plasma norepinephrine (NE) did not differ significantly among groups on placebo and was consistently reduced (P less than 0.05-0.001) by sympathetic blockade. The latter also decreased (P less than 0.05-0.001) plasma total cholesterol (C) as well as low and very low density lipoprotein cholesterol (LDL + VLDL-C) in the three patient groups. In the two dialysis groups, basal levels of plasma triglycerides (Tg) were increased and high density lipoprotein cholesterol (HDL-C) was diminished (P less than 0.01-0.001); sympathetic blockade lowered Tg and raised HDL-C (P less than 0.01-0.001). In normal subjects, sympathetic blockade did not significantly modify plasma lipoproteins. In the three patient groups, significant correlations (r = 0.62 - 0.88; P less than 0.05 - less than 0.001) existed between (a) basal plasma NE and total C or LDL + VLDL-C and (b) debrisoquine-induced changes in NE and changes in total LDL + VLDL-C. These findings suggest that in essential hypertension as well as in hemodialysis patients, the atherogenic C fraction, represented by LDL + VLDL-C, may be modulated by the noradrenergic activity.

Adult↗

PubMed1990

Therapeutic efficacy of the HMG-CoA-reductase inhibitor pravastatin in hyperlipoproteinaemia type II.

The efficacy and safety of the HMG-CoA-reductase inhibitor pravastatin was assessed in a double-blind, placebo controlled study. Thirty patients (51 y) with hyperlipoproteinaemia Type IIa (N = 22) or IIb (N = 8) received for 16 weeks either pravastatin 5 mg b.d. for 8 weeks followed by 10 mg b.d. for 8 weeks (Group I), or 10 mg b.d. for 8 weeks followed by 20 mg b.d. to 16 weeks (Group II), or placebo (Group III). In Groups I and II, mean serum total cholesterol was reduced by -26% and -22%, respectively; low-density lipoprotein (LDL)-cholesterol decreased by -28% and -27%, apolipoprotein B by -25% and -23%, and apolipoprotein E by -9% (NS) and -16%, respectively. Serum high-density lipoprotein (HDL)-cholesterol was increased by 11% in Group II, and so the total/HDL-cholesterol ratio fell by 33%. Apoprotein A1 and A2 were not significantly changed. No serious clinical and laboratory abnormalities were observed. The data suggest considerable therapeutic efficacy of pravastatin in the treatment of Type II hyperlipoproteinaemia.

Anticholesteremic Agents↗

PubMed1990

Atrial natriuretic factor and autonomic nervous system function in man.

To delineate a possible interaction of atrial natriuretic peptide ANF-(99-126) with autonomic nervous system function in humans, a spectrum of indices were assessed in 10 healthy young men during a 90 min iv administration of a) synthetic ANF-(99-126) 50 micrograms bolus followed by 0.025 micrograms.kg-1.min-1, b) the potent vasodilator sodium nitroprusside (SNP) 0.35 micrograms.kg-1. min-1, or c) vehicle 0.9% NaCl40 ml and 20% albumin 5 ml, in random sequence. Plasma immunoreactive ANF (irANF) rose from 32 to 1700 pg.ml-1 during the ANF-(99-126) infusion and was stable during SNP or vehicle. Infusion of ANF-(99-126) and SNP, but not vehicle, decreased diastolic blood pressure (BP) on average by -9 and -7.5%, respectively; systolic BP was largely unchanged. Heart rate (HR, + 15 and 12%) or plasma norepinephrine (NE) rose similarly during ANF-(99-126) and SNP infusions, and the systolic BP response to orthostasis was similar (-18 mmHg). The following autonomic indices did not differ significantly after the 3 infusions: responses of HR and NE to orthrostasis; reflex bradycardic response to phenylephrine (PE)-induced rise in systolic BP (+ 20 mmHg); responses of BP to hyperventilation, PE, or 3 min of sustained handgrip; and beat-to-beat variation (R-R interval) during deep breathing. The immediate orthostatic HR response (30/15 R-R interval ratio) fell similarly during infusion of ANF-(99-126) or nitroprusside. The findings indicate that in healthy men the function of the autonomic nervous system is not notably impaired by high circulating ANF levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1990

Insulin, insulin sensitivity and hypertension.

The sensitivity of tissue to insulin is of physiological, pathophysiological and therapeutic relevance. The quantity of insulin and the response to insulin are paramount complementary factors in the regulation of glucose metabolism, and may, at least under certain pathophysiological conditions, also affect cardiovascular function. Hypertension has a high prevalence among subjects with decreased insulin sensitivity and/or hyperinsulinaemia due to obesity, impaired glucose tolerance, non-insulin-dependent diabetes mellitus, and certain other conditions. There is evidence that, even in the absence of obesity or diabetes mellitus, essential hypertension tends to be associated with insulin resistance. The latter elicits a compensatory increase in insulin secretion. Hyperinsulinaemia also occurs in diabetes type 1 as a consequence of insulin treatment. Considering the acute effects of insulin on sympathetic nervous activity, transmembranous cation transport, renal sodium reabsorption, cellular proliferation and lipid metabolism, insulin resistance and/or hyperinsulinaemia may possibly contribute to the genesis of essential, obesity-associated and diabetes-associated hypertension, and may also promote dyslipidaemia in these disorders.

Blood Glucose↗