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Biomedical subjects

P Weidmann

Publications and source records attributed to P Weidmann.

At least 91 records · Page 5Linked to original sources
PubMed1990

Urodilatin, a natriuretic factor from kidneys, can modify renal and cardiovascular function in men.

Urodilatin is a newly identified analogue of human atrial natriuretic factor-(99-126) [ANF-(99-126)], which has recently been isolated from human urine and has 32 amino acid residues [ANF-(95-126)]. To investigate renal and cardiovascular effects in men, eight healthy subjects received injections of 25, 50, and 100 micrograms urodilatin iv compared with 50 micrograms ANF-(99-126) and placebo. Blood pressure decreased (P less than 0.05) after 50 micrograms ANF-(99-126), whereas urodilatin lowered diastolic blood pressure only at the highest dose (P less than 0.01). Heart rate increased (P less than 0.05-0.01) dose dependently after urodilatin injections. Glomerular filtration rate rose after 100 micrograms (from 120 +/- 3 to 156 +/- 7 ml.min-1.1.73 m-2, P less than 0.001) and 50 micrograms urodilatin (from 116 +/- 7 to 149 +/- 13 ml.min-1.1.73 m-2, P less than 0.01) but not after 25 micrograms urodilatin, ANF-(99-126), or placebo. Effective renal plasma flow was not significantly modified. Diuresis and excretion of sodium, chloride, and guanosine 3',5'-cyclic monophosphate increased (P less than 0.001) dose dependently; effects of 25 micrograms urodilatin equaled those of 50 micrograms ANF-(99-126). Plasma renin, aldosterone, and catecholamines were unchanged. We conclude that urodilatin can acutely modify renal and cardiovascular function in men and seems to exert more potent renal effects than ANF-(99-126).

Adult↗
PubMed1990

Dysregulation of atrial natriuretic factor in hypertension-prone man.

To evaluate the hypothesis of an atrial natriuretic factor (ANF) deficiency in hypertension-prone humans, we investigated plasma ANF and other variables in 116 white offspring of normotensive parents (ONorm) or essential hypertensive parents (OHyp). Ten ONorm and 10 OHyp, all men matched for age and body habitus, were studied after 4 days of low (70 mmol/day) and high (350 mmol/day) dietary sodium intake. After mild sodium restriction, plasma ANF did not differ between ONorm and OHyp (9.7 +/- 0.7 vs. 9.0 +/- 1.3 fmol/L). On high sodium intake, plasma ANF increased in ONorm, but not in OHyp (to 18.3 +/- 1.7 vs. 11.7 +/- 1.7 fmol/L; P less than 0.001). On the other hand, acute responses of plasma immunoreactive ANF (irANF) to saline loading or a norepinephrine-induced rise in blood pressure did not differ significantly between 8 ONorm and 8 OHyp. Fifty-one additional ONorm and 45 OHyp were evaluated during liberal sodium intake. Groups were further subdivided according to whether 24-h urinary sodium excretion was 91 mmol/m2 or less (modest salt intake) or more than 91 mmol/m2 (high salt intake). Twenty-four-hour urinary sodium was similar in the 26 ONorm and 21 OHyp on a modest salt intake (121 +/- 6 vs. 116 +/- 9 mmol) and in the 25 ONorm and the 24 OHyp on a high salt intake (226 +/- 10 vs. 221 +/- 9 mmol). However, compared with ONorm, plasma irANF in OHyp was slightly lower on modest sodium intake (7.7 +/- 0.7 vs. 5.3 +/- 0.7 fmol/L; P less than 0.05) and markedly reduced on high sodium intake (15.0 +/- 1.3 vs. 8.0 +/- 1.3 fmol/L; P less than 0.001). Moreover, the slope of the relationship between plasma irANF and 24-h urinary sodium was flatter in OHyp than in ONorm (z test = 2.4). We postulate a new endocrine syndrome characterized by a relative plasma ANF deficiency during high sodium intake in some hypertension-prone humans. This functional defect becomes apparent during chronic, rather than acute, stimulation of ANF release. It occurs as a familial disturbance and may potentially predispose to the development of hypertension.

Adult↗
PubMed1990

Insulin sensitivity in humans: alterations during drug administration and in essential hypertension.

Hypertension has a high prevalence among patients with noninsulin-dependent diabetes mellitus as well as in obese subjects, and glucose intolerance is emerging as a common feature to these conditions. There is increasing evidence that essential hypertension in nonobese, nondiabetic patients can be an insulin-resistant state per se. In view of the known acute effects of insulin on renal sodium retention, transcellular cation transport and perhaps also on sympathetic system, a possible involvement of insulin resistance in the genesis of essential hypertension deserves consideration. This point is of particular relevance not only because of the possible pathogenetic link between insulin resistance and high blood pressure, but also because of the potential metabolic interactions of certain drugs, especially in hypertensive diabetics. The oral glucose tolerance test, the glucose clamp and the minimal model approach represent three different methodological approaches that have been used to estimate insulin sensitivity in the intact organism. These methods differ with regard to their sensitivity, comparability and complexity. Although the oral glucose tolerance test has been widely used as standard approach to investigate drug-induced glucose intolerance, it does not provide a specific measure of insulin responsiveness. The insulin clamp introduced by Andres allows a direct quantification of insulin sensitivity, but its methodological complexity has limited its application in humans. The minimal model approach allows an accurate estimate and facilitates the assessment of insulin sensitivity under clinical conditions.

Blood Glucose↗
PubMed1990

[HMG-CoA-reductase inhibitors: a new principle in the treatment of hypercholesterolemia].

HMG-CoA reductase inhibitors are a new class of drugs, which inhibit de novo cholesterol biosynthesis and significantly reduces the blood cholesterol concentrations. Three separate inhibitors, lovastatin, simvastatin and pravastatin can lower plasma total cholesterol and low-density lipoprotein (LDL) levels in hypercholesterolemic humans by 20 to 30% and 30 to 40%, respectively. The reduction in the levels of circulating atherogenic lipoprotein particles occurs as a result of decreased synthesis and enhanced removal of LDLs by the LDL receptor pathway in hepatocytes. Moreover, the levels of high-density lipoprotein (HDL-)cholesterol, which are inversely related to atherosclerosis, increase with treatment by these drugs. If the short-term safety of these drugs extends to ongoing longterm studies and if cardiovascular morbidity and mortality are improved by their use, these hypolipidemic agents will facilitate the effective treatment of hypercholesterolemia.

Anticholesteremic Agents↗
PubMed1989

Stimulation of renin secretion by potassium-channel activation with cromakalim.

The cardiovascular and endocrine profile of cromakalim has been studied in 8 healthy men (age 25 +/- 2 years: means SEM) and its influence on renin release from cultured rat juxtaglomerular cells in vitro has also been examined. According to a double-blind, randomized sequence the subjects received placebo or cromakalim 1 mg as a single daily oral dose for 5 days. Compared to placebo, cromakalim significantly increased plasma renin activity (+ 122%; from 1.73 to 3.87 ng AI.ml-1.h-1), angiotensin II (+ 105%; from 5.1 to 10.5 pg.ml-1), and norepinephrine (+ 61%) levels, and heart rate (+ 8%). Plasma aldosterone, blood pressure and indices of the electrolyte-fluid volume state were unchanged. Cromakalim in vitro stimulated renin release, from 9.9 to 36.5 ng AI.h-1.30 min.mg cell protein, from juxtaglomerular cells. It appears that the presumed K+-channel activator cromakalim increases renin release in vivo at least in part by direct stimulation of renal juxtaglomerular cells.

Adult↗
PubMed1989

Antihypertensive and hypouricaemic effects of nitrendipine in chronic renal failure.

To evaluate the potential therapeutic value of calcium antagonists in hypertension associated with impaired renal function, blood pressure (BP), certain regulatory factors, and metabolic correlates of cardiovascular risk have been assessed in 15 patients with mild to marked chronic renal failure before and after 6 weeks of therapy with nitrendipine. Compared to placebo, nitrendipine (mean final dose 55 mg/day) decreased supine BP from 173/102 to 146/81 mm Hg and upright BP from 170/105 to 145/86 mm Hg. Heart rate, body weight (+0.8 kg) and exchangeable sodium (+176 mmol, not significant) were minimally increased, and plasma and whole blood volume, plasma angiotensin II and creatinine concentrations, and urinary electrolyte and creatinine excretion were not significantly changed. Nitrendipine increased uric acid excretion and lowered plasma uric acid by 24%; glucose, insulin, serum total lipids, and lipoprotein fractions were unchanged.

Adult↗
PubMed1989

Cardiovascular regulation and lipoprotein profile during administration of co-dergocrine in essential hypertension.

Co-dergocrine has recently been demonstrated acutely to lower plasma norepinephrine (NE) and blood pressure (BP) in patients with essential hypertension, and similar results have been obtained during chronic administration of co-dergocrine to healthy men. The present study investigated the effect of 3 weeks of treatment with co-dergocrine 4 mg/day on BP, plasma catecholamines, certain other BP-regulating factors and serum lipoproteins in patients with essential hypertension. Compared to placebo conditions, co-dergocrine decreased supine BP and heart rate by -7% and the upright plasma NE level by -24%. Supine plasma NE also fell (-24%). Total cholesterol and the LDL + VLDL-cholesterol lipoprotein fraction were lowered by -6%. No significant change was observed in plasma renin activity, angiotensin II, aldosterone and epinephrine levels, whole blood and plasma volume, exchangeable sodium, and the cardiovascular responsiveness to NE, angiotensin II and isoproterenol. The findings suggest that in patients with essential hypertension, chronic treatment with co-dergocrine may slightly decrease sympathetic outflow and, at least in the short-term, lower the potentially atherogenic serum LDL + VLDL - cholesterol fraction.

Adult↗
PubMed1989

Atrial natriuretic peptide in man.

The heart is the major source of atrial natriuretic peptides (ANP). A propeptide is stored in atrial myocytes. In normal humans, atrial distension secondary to volume overload and/or increased atrial pressures are thought to stimulate the secretion of biologically active alpha-ANP (ANF-[99-126], 28 amino residues) into the circulation. Plasma immunoreactive ANP (irANP) rises in response to acute sodium-volume loading, the central shift of volume produced by lying down or by immersion, acute increases in blood pressure (BP), dynamic exercise, or the administration of glucocorticoids or mineralocorticoids. Plasma irANP also rises with aging. Synthetic alpha-ANP infused acutely i.v. can lower BP, reduce plasma volume by an extravascular shift, cause baroreflex-mediated sympathetic activation, directly inhibit adrenal steroidogenesis and lower plasma aldosterone and cortisol, directly inhibit renal renin release, elevate plasma insulin; diuresis, free water clearance and natriuresis increase already in response to low alpha-ANP doses that raise plasma irANP within the physiological-pathological range. It follows that in addition to direct influences on cardiovascular and renal function, the ANP system may comprise a cardio-adrenal feedback mechanism and perhaps also modulate insulin and the release of ADH. The major although yet unproven physiological role of the ANP system may be the protection of the heart against volume and/or pressure overload. The pathophysiological, diagnostic and therapeutic aspects of elevated plasma irANP values, ANP measurements, or administration of synthetic ANP, respectively, in various diseases are currently under intense study and of great potential interest.

Atrial Natriuretic Factor↗
PubMed1989

Antihypertensive contribution of sodium depletion and the sympathetic axis during chronic angiotensin II converting enzyme inhibition.

The known physiological adaptation of cardiovascular sensitivity to variations in angiotensin II (Ang II) levels would predict that the blood pressure (BP)-lowering effect of Ang II inhibition might be at least partly counterbalanced by enhanced Ang II reactivity. Therefore, factors other than Ang II inhibition per se may contribute to the antihypertensive mechanisms of angiotensin converting enzyme (ACE) inhibitors. In order to further investigate this, the body sodium-blood volume state as well as the pressor reactivity to infused Ang II or norepinephrine (NE) were assessed in 12 normal subjects and 16 patients with essential hypertension given a placebo, and after 6 weeks of intervention with enalapril (20-40 mg/day). Enalapril produced in both groups similar falls in plasma ACE activity (P less than 0.0001) and upright plasma aldosterone (P less than 0.01), and a rise in plasma renin activity (PRA; P less than 0.05). BP decreased from 156/107 +/- 3/2 (mean +/- s.e.m.) to 142/94 +/- 5/3 mmHg (P less than 0.001) in the hypertensives and from 118/84 +/- 4/2 to 111/73 +/- 4/3 mmHg (P less than 0.01) in the normal subjects. In the hypertensive patients only, the Ang II pressor reactivity relative to Ang II plasma levels during Ang II infusion was increased (P less than 0.01), while the NE pressor reactivity relative to NE plasma levels during NE infusion (P less than 0.01) as well as the exchangeable body sodium (-5%, P less than 0.001) were reduced significantly. Blood and plasma volume, levels of plasma atrial natriuretic factor and catecholamines, and the heart rate and its response to isoproterenol were unchanged in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Distinct hemodynamic and renal effects of calcitonin gene-related peptide and calcitonin in men.

Cardiovascular and renal actions of human calcitonin gene-related peptide II (or beta) (CGRP) and of human calcitonin (CT) infused intravenously for 1 h each (79 and 263 pmol.kg-1.h-1) have been compared in normal men (n = 10 for CGRP, n = 6 for CT and vehicle alone). CGRP lowered diastolic blood pressure by 26% and increased the heart rate by 35% and raised plasma levels of norepinephrine, epinephrine, and dopamine and renin activity (P less than 0.01). The fractional excretion rates (FE) of sodium and chloride were doubled (P less than 0.05-0.01) in the presence of an unaltered glomerular filtration rate. CT, on the other hand, did not affect the diastolic blood pressure, but the stimulation of diuresis and of the FE of sodium and chloride was more pronounced with CT than with CGRP (P less than 0.01). Moreover, CT lowered serum calcium levels and stimulated urinary adenosine 3',5'-cyclic monophosphate and phosphate excretion (P less than 0.01). In conclusion, the cardiovascular effects of CGRP are contrasted by weaker renal tubular actions of the neuropeptide in relation to CT.

Adult↗
PubMed1989

Hypertensive dysregulation and its modification by calcium channel blockade in nonoliguric renal failure.

UNLABELLED: To investigate the pathogenetic constellation and its modification by calcium channel blockade in hypertension associated with chronic nonoliguric renal failure, blood pressure (BP), various pressor factors or correlates, cardiovascular responsiveness, and plasma atrial natriuretic peptide (ANP) were assessed in 15 hypertensive patients (serum creatinine 160-715 mumol/l) before and after 6 weeks of intervention with the agent nitrendipine. On placebo, these patients had a lower plasma angiotensin II (AngII) clearance and higher values of supine plasma AngII, aldosterone, norepinephrine (NE), and heart rate than healthy humans. Acute responses of BP to AngII and of heart rate to isoproterenol were blunted in the patients (p less than 0.05-0.001). Plasma ANP was elevated, correlated positively with systolic BP, and rose in response to NE pressor infusion (p less than 0.05-0.001). Exchangeable sodium and blood volume did not differ significantly from normal values. Nitrendipine reduced the cardiovascular responses to AngII, NE, and isoproterenol and lowered supine BP from 173/102 +/- 5/2 to 146/81 +/- 3/3 mm Hg and upright BP from 170/105 +/- 5/2 to 145/86 +/- 4/3 mm Hg (p less than 0.05-0.001); except for slightly increased plasma AngII, the levels of other endocrine variables, exchangeable sodium, blood volume, and creatinine clearance were not significantly modified. CONCLUSIONS: Hypertension accompanying chronic nonoliguric renal impairment seems to be strongly AngII and probably also NE dependent. Circulating ANP levels are high in this setting. Calcium channel blockade with nitrendipine effectively reduces cardiovascular AngII and NE dependence and BP.

Adult↗
PubMed1989

Hypotension and renal impairment during infusion of atrial natriuretic factor in liver cirrhosis with ascites.

Plasma immunoreactive atrial natriuretic factor (irANF) levels and the effects of alpha-human ANF (alpha-hANF) infusion were investigated in 7 patients with liver cirrhosis and ascites. Under basal conditions, supine blood pressure (BP) averaged 136/76 +/- 9/4 mm Hg (mean +/- SEM). Plasma irANF concentrations (124 +/- 33 pg/ml) were higher (p less than 0.01) than those in age-matched normal subjects (47 +/- 5 pg/ml). Plasma renin activity (PRA 5.9 +/- 2.2 ng/ml/h), aldosterone (18 +/- 7 ng/dl) and norepinephrine (NE, 66 +/- 5 ng/dl) levels were also elevated compared to the age-related normal range. Alpha-hANF infusion for 60 min at 0.036 micrograms/kg/min decreased the mean BP (-14%; p less than 0.05), increased PRA (+179%; p less than 0.05) and plasma NE (+24%; p less than 0.05). Glomerular filtration rate (GFR), effective renal plasma flow (ERPF), diuresis and natriuresis were not modified. A subsequent 60-min infusion of alpha-hANF at 0.067 micrograms/kg/min produced a marked fall in mean BP (-26%; p less than 0.001), hemoconcentration (hematocrit +6%; p less than 0.001) despite stable body fluid balance and a further increase in PRA (+350%, p less than 0.005). GFR and ERPF were severely reduced (-55 and -56%, respectively; p less than 0.001), while diuresis and natriuresis were not modified. Plasma aldosterone was unaltered during, but rose (+72%; p less than 0.01) after the cessation of alpha-hANF infusion. Variations in natriuresis during alpha-hANF infusion correlated positively with BP (r = 0.47; p less than 0.01), ERPF (r = 0.53; p less than 0.01) or GFR (r = 0.51; p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Pathogenetic and therapeutic relevance of cardiovascular pressor reactivity to norepinephrine in human hypertension.

In normotensive humans with a positive family history of essential hypertension, blood pressure (BP) is often dysregulated. Body sodium, blood volume, plasma angiotensin II (AngII), epinephrine and norepinephrine (NE), their responses to changes in sodium intake or posture, as well as baroreflex function, beta-receptor-mediated cardiac responsiveness, and the responsiveness of BP to AngII appear to be largely unaltered. However, the responsiveness of BP to NE is commonly exaggerated. An increase in potassium intake may improve the NE hyperreactivity and concomitantly lower BP within the "normotensive" range. Therefore, a selective vascular NE hyperreactivity relative to existing sympathetic activity seems to be a common familial abnormality predisposing for the development of essential hypertension. In borderline or established essential hypertension, an inappropriate vascular reactivity relative to sympathetic activity probably complements other mechanisms contributing to the maintenance of hypertension. Various antihypertensive treatments may lower BP at least in part by improving cardiovascular NE (hyper)reactivity without provoking an equivalent rise in sympathetic activity. These include dietary potassium supplementation, thiazide-type agents, indapamide, calcium channel blockers, postsynaptic alpha 1-blockers, and AngII converting enzyme inhibitors.

Animals↗
PubMed1989

Hypotensive and diuretic effects of atrial natriuretic factor in diabetic patients.

Plasma levels of atrial natriuretic factor (ANF), and the effects of intravenously infused ANF (99-126) on renal filtration and blood pressure, were studied during different sodium intakes in six patients with uncomplicated diabetes mellitus. The change from a low (25 mmol/day) to a high (241 mmol/day) sodium intake was associated with a 2.5 fold increase in circulating immunoreactive ANF. On both sodium diets, an infusion of synthetic ANF (99-126) given at two different rates caused a progressive decrease of arterial pressure. On a low but not on a high sodium intake arterial hypotension occurred in two patients. Moreover, on a high sodium intake, ANF did not significantly modify glomerular filtration rate, the effective renal plasma flow and the plasma concentrations of renin and aldosterone. It increased the fractional excretion of sodium by 72%. On a low sodium intake ANF caused a progressive fall of glomerular filtration rates and effective renal plasma flow. It increased the fractional excretion of sodium by 100%, and increased plasma renin and aldosterone levels. In patients with uncomplicated diabetes mellitus, circulating ANF responds physiologically to variations in sodium intake. A low sodium diet could predispose to arterial hypotension and renal functional impairment during infusion of ANF (99-126).

Adult↗