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Biomedical subjects

P Weidmann

Publications and source records attributed to P Weidmann.

At least 181 records · Page 10Linked to original sources
PubMed1984

Effects of nitrendipine and other calcium antagonists on glucose metabolism in man.

Some calcium antagonists, including nitrendipine, were noted to cause a dose-dependent and reversible inhibition of insulin release in certain animal models. Therefore, it is important to know the effects of clinical treatment with calcium antagonists in nondiabetic or diabetic man. A review of the literature allows the following conclusions: Acute and short-term therapy with calcium antagonists in nondiabetic and diabetic individuals did not change glucose homeostasis assessed with or without a glucose load. Nevertheless, higher doses of calcium antagonists were occasionally noted to slightly impair glucose homeostasis in nondiabetics, whereas, in some studies of diabetics, a slight amelioration or deterioration of glucose tolerance was variably reported. In long-term studies, the longest extending over 5 years, no change in basal or in glucose-stimulated carbohydrate metabolism was apparent in nondiabetic or diabetic subjects. These results are corroborated by our placebo-controlled observations during antihypertensive monotherapy with nitrendipine in Type II diabetics. Thus, glucose and insulin profiles and areas under the curve, before and following standard breakfast, were not altered following nitrendipine treatment periods of 6 weeks and 6 months, respectively. Concomitant blood levels of HbA1 on nitrendipine also were not different from those on placebo. The available information indicates that calcium antagonists probably do not affect glucose homeostasis to a clinically relevant degree, although some minor influences especially of higher dosages cannot be excluded.

Blood Glucose↗
PubMed1984

Body sodium blood volume state in essential hypertension: abnormal relation of exchangeable sodium to age and blood pressure in male patients.

The circulatory volume and exchangeable sodium (NaE) were measured by the Berne group in 110 normal subjects and 12 patients with benign untreated essential hypertension. Total plasma volume (PV) and blood volume (BV) correlated with total NaE (r = 0.64-0.75, p less than 0.001); these correlations were similar in normal and hypertensive subjects. PV, BV, and NaE related to body surface area averaged normal in the hypertensive population. PV and BV were unrelated to age or blood pressure in both normal and hypertensive subjects; NaE correlated positively with age (r = 0.25, p less than 0.02) and arterial pressure (r = 0.25, p less than 0.02) in essential hypertensive but not in normal subjects. These relationships in essential hypertension confirmed a previous observation by the Glasgow group. Moreover, a combined analysis of both study populations, with a total of 211 hypertensive patients, revealed significant correlations between NaE and age (r = 0.38, p less than 0.001) or arterial pressure (r = 0.40, p less than 0.001) in male but not in female subjects. The NaE was significantly decreased in hypertensive males less than 35 years old as compared with appropriate controls (95.8 +/- 5.1 vs 99.1 +/- 6.5%, p less than 0.02). BV and body sodium content are on average normal in patients with benign essential hypertension. The NaE may even be decreased in young male patients. These observations do not support the concept that body sodium and fluid volume expansion represent the initial event leading to high blood pressure in patients with essential hypertension.

Adolescent↗
PubMed1984

Circulatory volume in essential hypertension. Relationships with age, blood pressure, exchangeable sodium, renin, aldosterone and catecholamines.

The circulatory volume and exchangeable sodium were measured in 110 normal subjects and 120 patients with benign untreated essential hypertension. The two study groups did not differ in age, sodium and potassium metabolism, and plasma levels of renin, aldosterone and norepinephrine, while plasma epinephrine was slightly higher in essential hypertension. Total plasma and blood volume correlated with total exchangeable sodium (r = 0.64-0.75; p less than 0.001); these correlations were similar in normal and hypertensive subjects. Body surface area was found to be the most appropriate frame of reference for judging individual values of plasma and blood volume or exchangeable sodium; using this approach these body constituents were on average normal in the hypertensive population. Blood volume was unrelated to age or blood pressure in normal and hypertensive subjects. Exchangeable sodium tended to increase with age (r = 0.25; p less than 0.02) and correlated positively with blood pressure (r = 0.25; p less than 0.02) in essential hypertension but not in normal subjects. The latter body constituent was slightly but significantly decreased in hypertensive males aged less than 35 years as compared with appropriate normal controls (96.1 +/- 6.8% versus 99.6 +/- 6.7%; p less than 0.05). These findings confirm that blood volume and exchangeable sodium are on average normal in patients with benign essential hypertension. Body sodium may even be decreased in certain young hypertensive patients. These observations do not support the concept that hypervolemia may represent the initial event leading to high blood pressure in essential hypertension; in contrast, changes in blood volume appear to reflect variations in blood pressure.

Adolescent↗
PubMed1984

Correction of cardiovascular hypersensitivity to norepinephrine by potassium supplementation in normotensive members of hypertensive families and patients with essential hypertension.

Blood pressure (BP), plasma levels of norepinephrine (NE) and epinephrine, the chronotropic effect of isoproterenol, and the relationship between variations in BP and concomitant plasma NE levels obtained during NE infusion were studied under control conditions and after 10 days of dietary potassium supplementation (100 mmol/day) in 12 normotensive subjects with negative family history (FH) of hypertension (mean BP 111/70 +/- 9/7 mmHg), 11 normotensive subjects with positive FH (112/73 +/- 8/6 mmHg), and 10 subjects with untreated borderline to mild essential hypertension (131/89 +/- 15/9 mmHg). Under control conditions, the increase in circulating NE required to elevate mean BP by 20 mmHg was significantly lower in hypertensive subjects (6.1 +/- 4.0 nmol/l) or normotensive subjects with positive FH (5.0 +/- 2.4 nmol/l) than in normal subjects with negative FH (9.9 +/- 6.4 nmol/l); the other study parameters were similar. After potassium supplementation, plasma and urinary potassium increased and body weight decreased slightly in all groups; basal plasma NE and epinephrine levels and cardiovascular effects of isoproterenol were unchanged. However, in normotensive subjects with positive FH and hypertensive subjects, the increase in plasma NE required to elevate mean BP by 20 mmHg was normalized (to 8.9 +/- 5.9 and 9.9 +/- 6.9 nmol/l, respectively), while BP tended to decrease slightly. These findings indicate that dietary potassium supplementation may favorably modify noradrenergic BP-regulation in hypertension prone individuals.

Adult↗
PubMed1984

Pressor factors and cardiovascular pressor responsiveness after short-term antihypertensive therapy with the calcium antagonist nifedipine alone or combined with a diuretic.

Exchangeable sodium, blood volume, plasma norepinephrine, epinephrine, renin levels, and pressor responses to infused norepinephrine or angiotensin II were assessed in 10 patients with essential hypertension on placebo, following six to eight weeks of monotherapy with nifedipine, 3 X 10-20 mg/day, and after six to eight weeks on nifedipine combined with the diuretic chlorthalidone, 25 to 50 mg/day. Supine blood pressure was decreased after nifedipine alone (P less than 0.05) and even further after nifedipine + chlorthalidone (P less than 0.01). Body weight and exchangeable sodium increased after nifedipine (P less than 0.05), but were decreased after adding chlorthalidone. Blood volume was unchanged after nifedipine, but was reduced on nifedipine + chlorthalidone (P less than 0.05). Heart rate, supine plasma renin, catecholamine levels, and pressor responses to norepinephrine or angiotensin II were not consistently changed on nifedipine alone or combined with chlorthalidone. These findings indicate that in the established phase of treatment, nifedipine may exert its antihypertensive effect without necessarily altering cardiovascular responsiveness to norepinephrine and angiotensin II. Moreover, mild sodium retention may develop on nifedipine at least in some hypertensive patients.

Adult↗
PubMed1983

[Long-term treatment of hypertension in 1983].

Persons with either borderline or established hypertension should always be instructed in a series of general measures. These include a reduction of overweight, dietary salt restriction, no smoking, whenever possible discontinuation of oral contraceptives, appropriate physical exercise, and treatment, primarily by diet, of a coexisting hyperlipidemia. Such non-pharmacologic measures may often improve the potential risk constellation and in some persons with borderline or mild hypertension even normalize the blood pressure. Pharmacotherapy is recommended only in selected cases with persistent borderline blood pressure elevation but, on a partly empirical basis, appears usually to be indicated for established hypertension of greater than or equal to 160/95 mm Hg. The coexistence of diabetes mellitus or renal functional impairment and advancing age of a patient deserve special consideration in the choice and/or dosage of antihypertensive drugs. Failure to achieve satisfactory blood pressure control through general measures and appropriately dosed triple drug therapy (including a diuretic, a betablocker or other sympatholytic or calcium antagonist, and (di)hydralazine, prazosin or endralazine) calls for thorough reevaluation of the situation. Causes which may simulate or induce resistant hypertension include technical problems with measurement, oral contraceptives, insufficient patient cooperation, sodium fluid volume retention, insufficient pharmacotherapy, drug interactions, "office hypertension" with satisfactory blood pressure in the patient's daily environment, and potentially operable causes such as renal artery stenosis or pheochromocytoma. If none of these factors is present, persistent uncontrolled hypertension can very often be treated satisfactorily with newer potent drugs such as the convertase inhibitor captopril as first choice agent in women, or the direct vasodilator minoxidil as the preferred agent in men. Together with the necessary steps to improve patient compliance, including increased blood pressure measurements by the patient himself, practitioners can now rely upon effective therapeutic tools. The present social and economic burden resulting for the individual and the public from neglected therapeutic opportunities, from excess morbidity and early death due to inadequately treated hypertension, can and must be reduced in the interests of the community at large.

Adolescent↗
PubMed1983

Constant kinetics and constant concentration-effect relationship during long-term beta-blockade with pindolol.

Long-term beta-blockade is said to increase the number of beta-receptors. The effect of beta-blockers could therefore be reduced after long use. We tested this hypothesis in nine healthy subjects given 15 mg pindolol daily for 4 wk. Plasma concentrations (measured fluorometrically), isoproterenol dose-response relationship (to calculate the dose needed to increase heart rate by 25 bpm), renin, epinephrine, and norepinephrine were measured several times before and after the first and last dose. Kinetic parameters remained stable: total clearance (Cltot) = 45.2 and 42.9 l/hr, and Vdss = 205.8 and 198.6 l after the first and last dose. The concentration-effect relationship, plotted as the "dose ratio minus one" against the log of the plasma concentration was identical after 4 wk. Basal plasma renin activity was reduced slightly and the increase of stimulated plasma renin was blunted by pindolol even after 4 wk. The initial lowering of unstimulated renin by pindolol in the first 2 hr after dosing was not detectable after 4 wk. Epinephrine and norepinephrine levels in plasma were not changed initially nor after 4 wk. It is concluded that pindolol has a stable kinetic profile over time and that its beta-blockade does not induce tachyphylaxis.

Adult↗
PubMed1983

Antihypertensive mechanism of diuretic treatment with chlorthalidone. Complementary roles of sympathetic axis and sodium.

Twenty-three patients with untreated mild to moderate essential hypertension had on the average an abnormally increased cardiovascular pressor responsiveness to exogenous norepinephrine (NE), while plasma and urinary NE, exchangeable body sodium and blood volume were normal. An increased pressor responsiveness to angiotensin II in these patients was associated with a tendency for low plasma renin activity (PRA). Compared to placebo conditions, treatment with chlorthalidone, 100 mg/day, for 6 weeks significantly decreased blood pressure and exchangeable sodium in these hypertensive patients but not in ten normal subjects; blood volume and heart rate were unchanged in both groups. Chlorthalidone induced a marked increase in PRA, but only a mild increase in angiotensin II pressor dose. In contrast, the diuretic caused a greater increase in NE pressor dose than in plasma NE in the hypertensive group, thus improving the disturbed relationship between plasma NE and NE responsiveness in these patients. No significant modification of plasma NE and NE responsiveness occurred in diuretic-treated normal subjects. In addition to sodium and the renin-angiotensin system, the sympathetic regulatory axis seems to be involved in the antihypertensive mechanism of chlorthalidone. Thiazide-like diuretics may decrease blood pressure in essential hypertension in part by lowering an abnormally high cardiovascular NE responsiveness without causing an equivalent increase in circulating NE.

Adult↗
PubMed1983

Acute effects of combined vasodilation and beta-adrenoceptor blockade with prizidilol on renal function.

1 The effects of a single oral dose of 600 mg of prizidilol on renal function were studied 5 to 6 h after dosing in six normal subjects and eight patients with essential hypertension. 2 Mean arterial blood pressure was reduced to 92% of the control value in normal subjects and to 75% in hypertensive patients. Heart rate increased slightly. 3 In normal subjects, effective renal plasma flow was increased to 107% of control values while glomerular filtration rate (83%), filtration fraction (79%), sodium (84%) and potassium (50%) clearances were significantly decreased. 4 In hypertensive subjects, effective renal plasma flow was increased to 120% of control values, while glomerular filtration rate (67%), filtration fraction (57%), sodium (27%) and potassium (72%) clearances were significantly decreased. 5 Plasma noradrenaline increased significantly in normal subjects (150%) and in patients (173%). Plasma renin activity, aldosterone and epinephrine levels did not change consistently. 6 The results indicate that the acute effects of prizidilol on blood pressure and renal function are more marked in hypertensive than in normotensive subjects. Prizidilol increases renal plasma flow like hydralazine and depresses glomerular filtration rate and fractional sodium excretion like endralazine. In addition to the fall in arterial pressure, efferent vasodilation and/or a specific effect on the glomerular ultrafiltration coefficient Kf may account for the striking decrease in filtration fraction.

Adrenergic beta-Antagonists↗
PubMed1983

Correction of altered noradrenaline reactivity in essential hypertension by indapamide.

Fourteen patients with untreated mild to moderate essential hypertension had, on average, an abnormally high cardiovascular reactivity to exogenous noradrenaline and angiotensin II, while plasma noradrenaline, renin activity, exchangeable body sodium, and blood volume were normal. Treatment with a low dose of indapamide (2.5 mg/day) for 6 weeks decreased blood pressure by 10% in these hypertensive patients but not in 13 normal control subjects. Plasma or blood volume and exchangeable sodium were not changed significantly; nevertheless, the latter, and body weight, tended to be decreased slightly. Though a mild reduction in extracellular sodium in both normal and hypertensive subjects appears possible, it may not fully explain per se the blood pressure-lowering effect of indapamide in essential hypertension. Indapamide induced a mild decrease in angiotensin II pressor responsiveness in normal or hypertensive subjects, but a possible depressor influence from this change was probably antagonized by a concomitant pronounced increase in plasma renin activity. In hypertensive patients, the abnormally high noradrenaline reactivity was corrected by indapamide without an accompanying increase in endogenous plasma noradrenaline levels. Indapamide-induced changes in blood pressure correlated with those in noradrenaline pressor dose. It was concluded, therefore, that indapamide may decrease blood pressure in essential hypertension at least in part by lowering an abnormally high cardiovascular noradrenaline reactivity without causing an equivalent increase in adrenergic nervous activity.

Adolescent↗
PubMed1983

Effects of indapamide and various diuretics alone or combined with beta-blockers on serum lipoproteins.

A prospective evaluation was started in 1976 to study the influence of diuretics alone or combined with beta-blockers on serum lipoproteins in normal or hypertensive subjects. Compared to placebo conditions, 4 or 6-weeks' monotherapy with various diuretics significantly (p less than 0.05) increased the beta-lipoprotein fraction (furosemide, 80 mg/day or chlorthalidone, 100 mg/day; n = 16) or low-density lipoprotein-cholesterol (LDL-C) (chlorthalidone, 100 mg/day, n = 27 men; tienilic acid, 250 mg/day, n = 16 men, clopamide, 5 mg/day, n = 17 men; or muzolimine, 20 to 40 mg/day, n = 13 men or post-menopausal women). No increase in LDL-C was noted in 43 men (32 normal, 11 with mild hypertension) treated with indapamide, 2.5 mg/day. Serum high-density lipoprotein-cholesterol and apoproteins A1, A2 and B were not consistently changed by any of these agents. In women, chlorthalidone (100 mg/day) significantly increased LDL-C in the (100 mg/day) significantly increased LDL-C in the post-menopausal (n = 18) but not in the pre-menopausal (n = 22) state. Increases in LDL-C caused by chlorthalidone monotherapy were prevented or reversed by the addition of a beta-blocker, usually propranolol or atenolol (n = 18); increases in LDL-C during clopamide monotherapy were reversed after the addition of the beta-blocker pindolol (10 mg/day, n = 17). In all studies, variations in beta-lipoprotein or LDL-C levels could not be explained by changes in blood volume, serum glucose or insulin and did not correlate with alterations in blood pressure, plasma potassium, renin, aldosterone, adrenaline or noradrenaline. These observations indicate that various diuretics may increase serum LDL-C in men or post-menopausal women. Pre-menopausal women may often be protected from this side-effect. Long-term studies are now needed to clarify the pathogenic and prognostic relevance of lipoprotein changes induced by diuretics. In the meantime, it is of clinical interest that indapamide had no significant effect on serum lipoproteins and that certain beta-blockers appear to prevent or reverse increases in LDL-C during diuretic treatment in men and post-menopausal women.

Adrenergic beta-Antagonists↗
PubMed1983

Responsiveness of plasma 18-hydroxycorticosterone and aldosterone to angiotensin II or corticotropin in nonazotemic diabetes mellitus.

To assess the function of the final step of the pathway for aldosterone biosynthesis, the responsiveness of plasma 18-hydroxycorticosterone and aldosterone concentrations to angiotensin II infusion was studied in 14 patients with nonazotemic diabetes mellitus as compared with 14 normal controls approximately matched for sex and age. In addition, the responses of both steroids to corticotropin injection were investigated in the diabetic patients. Under basal conditions, plasma aldosterone levels were slightly lower in the patients than in normal controls, while plasma 18-hydroxycorticosterone concentrations were similar in the two study groups. Angiotensin II induced marked and comparable increases in plasma 18-hydroxycorticosterone and aldosterone levels in normal and diabetic subjects. Plasma 18-hydroxycorticosterone and aldosterone levels before and after angiotensin II infusion were significantly interrelated; this correlation was similar in normal subjects (r = 0.61; P less than 0.001) and diabetic patients (r = 0.51; P less than 0.005). Plasma 18-hydroxycorticosterone and aldosterone were significantly increased by corticotropin in the patients. These findings indicate that the terminal step of aldosterone biosynthesis, which involves the production of 18-hydroxycorticosterone and aldosterone, is largely unaltered in patients with nonazotemic diabetes mellitus.

18-Hydroxycorticosterone↗
PubMed1983

Different blood pressure responses to diuretic treatment in normotensive subjects with and without a family history of hypertension.

The possibility that the familial background for hypertension may influence the blood pressure response to diuretic treatment was evaluated in 14 normotensive subjects with negative and 14 normotensive subjects with positive family history of hypertension. Under control conditions, blood pressure, heart rate, body weight, urinary sodium and potassium, plasma sodium, potassium, creatinine, norepinephrine, epinephrine, renin and aldosterone levels did not differ between the two study groups. Each subject received chlorthalidone, 100 mg/day, or indapamide, 2.5 mg/day for eight weeks. Compared with control values, blood pressure was decreased during diuretic treatment in subjects with positive (P less than 0.05), but not in those with negative family history for hypertension. Diuretic-induced decreases in plasma potassium (P less than 0.005), increases in plasma renin activity and aldosterone (P less than 0.005), and a tendency towards higher plasma norepinephrine levels were not different between the two study groups. These findings suggest that the familial background of hypertension may, at least in part, determine the blood pressure response to diuretic treatment.

Adult↗
PubMed1982

[Hyporeninemic hypoaldosteronism and the differential diagnosis of hyperkalemia].

Selective hypoaldosteronism is defined as diminished production of aldosterone, and sometimes also of 18-hydroxycorticosterone, with otherwise intact adrenal function. A decrease in the secretion of potassium and H+-ions and in the reabsorption of sodium in the distal nephron may result and lead to hyperkalemia, hyperchloremic acidosis, and impaired renal sodium conservation. The form of hypoaldosteronism which occurs in the adult is characterized by the following additional features: the aldosterone deficiency is due in the majority of cases to a decrease in enzymatically active plasma renin ("hyporeninemic hypoaldosteronism"), while various endogenous mechanisms as well as certain drugs (prostaglandin inhibitors, beta-blockers) may contribute. Other disturbances of the renin-angiotensin system (e.g. during treatment with converting-enzyme inhibitors) may rarely be responsible. Abnormalities in adrenal cortical synthesis may sometimes coexist, but proof that adrenal enzymatic defects play a primary pathogenic role in selective hyperaldosteronism in the adult is lacking. Such patients are frequently older (greater than 50 years), and often have diabetes mellitus and/or nephropathy (diabetic, interstitial, or hydronephrosis). Hyperkalemia and acidosis tend particularly to develop in association with mild to moderate impairment of renal function. The differential diagnosis should include other causes of impaired renal potassium secretion (Addison's disease, renal resistance to mineralocorticoids, potassium-sparing diuretics). Moreover, possible extrarenal factors contributing to hyperkalemia (oral potassium intake and redistribution of intracellular/extracellular space, particularly with associated insulin deficiency) should also be considered. For treatment, dietary potassium restriction is recommended as a general step. Replacement with the mineralocorticoid fludrocortisone acetate usually reverses the hyperkalemia and acidosis, but may sometimes induce sodium retention and hypertension. Loop diuretics, potassium-exchanging preparations and/or bicarbonate may also be useful as alternatives or additives.

Acid-Base Equilibrium↗
PubMed1982

Serum lipoproteins in patients with mild renal disease treated with the diuretic muzolimine.

Patients with renal functional impairment are prone to develop hypertension and hyperlipidemia, and both abnormalities tend to occur already at an early stage of kidney disease. In 18 patients with mild renal disease (glomerular filtration rate 65 +/- 5 ml/min) and hypertension (mean blood pressure 126 +/- 4 mm Hg), the effect of six weeks of treatment with the loop-diuretic muzolimine on serum lipoproteins was assessed. Compared to placebo values, the diuretic significantly increased serum low-density lipoprotein cholesterol (LDL-C) and apoprotein B (+ 18 and 11%, respectively, P less than 0.005) in 13 men or postmenopausal women, but not in 5 premenopausal women. Serum high-density lipoprotein cholesterol (HDL-C), and total triglycerides or lipoprotein triglyceride fractions were not consistently changed in both subgroups. Thus, the ratio LDL-C/HDL-C was increased from 3.2 +/- 0.3 to 3.9 +/- 0.3 (P less than 0.05) in the men or postmenopausal women, while no such tendency occurred in the premenopausal women (4.1 +/- 0.6 to 3.7 +/- 0.6). Changes in serum LDL-C were not associated with hemoconcentration or alterations in carbohydrate metabolism and were not related to variations in serum potassium or blood pressure. Increased serum levels of the atherogenic LDL-C fraction during diuretic treatment in men or postmenopausal women with renal disease may represent a potentially undesirable effect, particularly since such patients may tend to have hyperlipidemia in the untreated state.

Female↗