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Biomedical subjects

P Weidmann

Publications and source records attributed to P Weidmann.

At least 109 records · Page 6Linked to original sources
PubMed1988

Effect of various therapeutic approaches on plasma potassium and major regulating factors in terminal renal failure.

PURPOSE: The development of life-threatening hyperkalemia poses a risk for patients with chronic preterminal renal failure. Various therapeutic options have been suggested for hyperkalemic emergencies in these patients; to date, however, no study has evaluated the relative efficacies of these measures in the presence of renal failure. Our goal was to examine the acute effects of a variety of therapeutic approaches, as well as those of hemodialysis, on plasma potassium levels in a hemodialysis population. PATIENTS AND METHODS: Ten patients with terminal renal failure undergoing maintenance hemodialysis were enrolled in the study. Blood gas parameters and plasma sodium, potassium, glucose, osmolality, renin, aldosterone, epinephrine, norepinephrine, dopamine, and insulin were measured before, during, and after 60-minute infusions of bicarbonate, epinephrine, and insulin in glucose, and before, during, and after performance of regular hemodialysis for one hour. RESULTS: Hypertonic as well as isotonic intravenous bicarbonate (2 to 4 mmol/minute) induced a marked rise in plasma bicarbonate and pH, but failed to lower the plasma potassium level (5.66 versus 5.83 mmol/liter before and after). Epinephrine, 0.05 microgram/kg/minute administered intravenously, decreased plasma potassium only slightly from 5.57 to 5.25 mmol/liter, and five patients showed no decline. On the other hand, insulin in glucose, 5 mU/kg/minute intravenously, effectively lowered plasma potassium levels from 5.62 to 4.70 mmol/liter, and hemodialysis induced the most rapid decline from 5.63 to 4.29 mmol/liter. Plasma aldosterone was elevated before treatment; it correlated with plasma potassium and dropped during intravenous bicarbonate administration or hemodialysis. Pretreatment plasma renin activity, insulin, epinephrine, norepinephrine, and dopamine levels were generally normal. CONCLUSION: We conclude that in patients with terminal renal failure undergoing maintenance hemodialysis, intravenous bicarbonate is ineffective in lowering plasma potassium rapidly, and epinephrine is effective in only half the patients, whereas insulin in glucose is a fast and reliable form of therapy for hyperkalemic emergencies. Plasma aldosterone levels are appropriate in relationship to plasma potassium levels, and levels of other potassium-influencing hormones are generally normal.

Adult↗
PubMed1988

Metabolic effects of calcium antagonists in humans, with emphasis on carbohydrate, lipid, potassium, and uric acid homeostases.

Since metabolic side effects of conventional antihypertensive drugs could be one reason for the lack of improvement of cardiac morbidity and mortality, metabolic neutrality has become an important postulate of newer products such as the calcium antagonists (CA). Carbohydrate homeostasis--in spite of an anticipated deterioration derived from early in vitro experiments--has mostly been unaffected by CA therapy in humans, nondiabetic and diabetic. This was found in long-term studies in particular, whereas in acute or short-term trials with high dosages, minor alterations of insulin secretion and/or action were sometimes noted. These are negligible from a clinical point of view. Serum lipid profiles also were generally not disturbed by CA treatment, since most of the controlled long-term trials showed no change or even a potentially beneficial change. Minor lowering of plasma potassium levels during a CA regimen was exceptional and a rise of plasma uric acid values never reported; the latter may even decrease under certain circumstances. Thus, after reviewing more than 150 pertinent publications, we can state that the benefit of antihypertensive or antianginal treatment with a CA is in all likelihood not compromised by introducing known untoward metabolic cardiovascular risks.

Calcium Channel Blockers↗
PubMed1988

Effect of a new somatostatin analogue SMS 201-995 (Sandostatin) on the renin-aldosterone axis.

The effects of a new somatostatin analogue SMS 201-995 (H-D-Phe-Cys-Phe-D-Trp-Lys-Thr-Cys-Thr(ol), Sandostatin) on the orthostatic stimulation of plasma renin activity (PRA) following head-up tilting and on angiotensin II (Ang-II) induced aldosterone (PA) release were studied under placebo controlled conditions in separate groups of healthy volunteers consisting of six and 10 subjects, respectively. Head-up tilting (by 60 degrees) produced the characteristic increases in PRA and PA. Administration of SMS 201-995 significantly (P less than 0.05) inhibited this PRA elevation from 30 min on. Throughout the study period, PA levels were not consistently altered by this analogue. Furthermore, SMS 201-995 failed to inhibit the stimulation of PA secretion induced by exogenous angiotensin-II (2-10 ng/kg/min). Results presented here are at variance with data collected with natural somatostatin showing an inhibitory effect on stimulated PA. This discrepancy can be explained by the recently described absence of SMS 201-995 binding sites in primate adrenal cortex and in human aldosteronomas.

Adult↗
PubMed1988

Atrial natriuretic peptide in acute mountain sickness.

To test the hypothesis that elevated atrial natriuretic peptide (ANP) may be involved in altered fluid homeostasis at high altitude, we examined 25 mountaineers at an altitude of 550 m and 6, 18, and 42 h after arrival at an altitude of 4,559 m, which was climbed in 24 h starting from 3,220 m. In 14 subjects, symptoms of acute mountain sickness (AMS) were absent or mild (group A), whereas 11 subjects had severe AMS (group B). Fluid intake was similar in both groups. In group B, urine flow decreased from 61 +/- 8 (base line) to 36 +/- 3 (SE) ml/h (maximal decrease) (P less than 0.05) and sodium excretion from 7.9 +/- 0.9 to 4.6 +/- 0.7) mmol.l-1.h-1 (P less than 0.05); ANP increased from 31 +/- 4 to 87 +/- 26 pmol/l (P less than 0.001), plasma aldosterone from 191 +/- 27 to 283 +/- 55 pmol/l (P less than 0.01 compared with group A), and antidiuretic hormone (ADH) from 1.0 +/- 0.1 to 2.9 +/- 1.2 pmol/l (P = 0.08 compared with group A). These variables did not change significantly in group A, with the exception of a decrease in plasma aldosterone from 189 +/- 19 to 111 +/- 17 pmol/l (P less than 0.01). There were no measurable effects of elevated ANP on natriuresis, cortisol, or blood pressure. The reduced diuresis in AMS may be explained by increased plasma aldosterone and ADH overriding the expected renal action of ANP. The significance of elevated ANP in AMS remains to be established.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Atrial natriuretic factor in mild to moderate chronic renal failure.

The relationship between kidney function and plasma immunoreactive atrial natriuretic factor (irANF) levels as well as the effects of synthetic human ANF-(99-126) were investigated in 13 patients with mild to moderate chronic renal failure. Under basal conditions, glomerular filtration rate averaged 39 +/- 5 (SEM) ml/min/1.73 m2 and blood pressure (BP) averaged 166/107 +/- 7/2 mm Hg; 12 patients were hypertensive. Plasma irANF levels were significantly increased (98 +/- 16 vs 42 +/- 4 pg/ml in healthy control subjects; p less than 0.001) and correlated (p less than 0.05-0.005) inversely with hematocrit (r = -0.65) and positively with systolic BP (r = 0.75) or fractional sodium excretion (r = 0.75). Human ANF-(99-126) infusion for 45 minutes at 0.034 microgram/kg/min augmented (p less than 0.05-0.01) diuresis and urinary sodium, chloride, calcium, phosphate, and magnesium excretion. During the subsequent 45 minutes of human ANF-(99-126) infusion at a rate of 0.077 microgram/kg/min, diuresis and electrolyte excretion remained elevated (p less than 0.05-0.01). Glomerular filtration rate and effective renal plasma flow were not significantly modified, but filtration fraction rose progressively (p less than 0.01). Human ANF-(99-126) infusion decreased BP (p less than 0.05-0.01), produced hemoconcentration (hematocrit + 7%; p less than 0.01) without negative body fluid balance, and increased (p less than 0.01-0.001) plasma norepinephrine, insulin, and serum free fatty acids; plasma aldosterone and renin activity were unaltered during but rose after cessation of human ANF-(99-126) infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Calcitonin gene-related peptide is a stimulator of renin secretion.

Calcitonin gene-related peptide (CGRP) was found to stimulate renin secretion in vivo in normal human volunteers. Moreover, CGRP stimulated the release of renin in vitro from isolated rat renal juxtaglomerular cells (half-maximal effective concentration [EC50] 100 nM) concomitant with stimulation of cAMP production (EC50 60 nM). Immunoreactive CGRP was recognized in rat renal cortical nerve fibers, and intact rat CGRP was identified in extracts of the rat renal cortex. Because CGRP containing sensory nerve fibers are seen in the region of the juxtaglomerular apparatus, it would seem that the release of CGRP from these afferent nerves may be involved in the physiological control of renin secretion.

Animals↗
PubMed1988

Glucocorticoid and mineralocorticoid stimulation of atrial natriuretic peptide release in man.

To investigate the influence of a mineralocorticoid and a glucocorticoid on plasma immunoreactive atrial natriuretic peptide (irANP) and possible functional correlates, eight normal men received in random order 9 alpha-fludrocortisone acetate (9 alpha F; 0.6 mg/day), prednisone (50 mg/day), and placebo each for 9 days. Their diet contained 130 mmol sodium and 75 mmol potassium daily. The mean supine plasma irANP levels were similar on days 2, 4, and 9 of placebo treatment [25 +/- 10 (+/- SE), 27 +/- 5, and 27 +/- 6 pmol/L, respectively]. Mean plasma irANP levels were 76 +/- 42 (P less than 0.05), 89 +/- 34, and 93 +/- 29 pmol/L (P less than 0.01), respectively, on days 2, 4, and 9 during 9 alpha F administration, and 68 +/- 37 (P less than 0.05), 83 +/- 41, and 48 +/- 18 pmol/L on the same days during prednisone administration. Compared with the placebo period, sodium intake minus urinary output during 9 alpha F administration averaged +41 mmol at the time of blood sampling on day 2, +112 mmol on day 4, and +149 mmol on day 9; body weight was unchanged on day 2 and increased by 0.7 and 1.1 kg on days 4 and 9, respectively. Escape from 9 alpha F-induced renal sodium retention occurred on days 5 and 6. During prednisone administration, sodium intake minus urinary output and body weight did not change. Plasma volume and BP rose significantly during 9 alpha F (P less than 0.05) but not during prednisone administration. Plasma renin, aldosterone, and norepinephrine (NE) decreased during 9 alpha F treatment (P less than 0.05 to less than 0.01); during prednisone treatment, plasma aldosterone levels were lower on day 9 only. Cardiovascular pressor responsiveness to angiotensin II was enhanced during 9 alpha F but not prednisone administration, while blood pressure reactivity to NE was not significantly modified. These findings demonstrate that 9 alpha F and prednisone in high doses provoke remarkably similar increases in plasma irANP, but that the glucocorticoid-induced rise in plasma irANP is due to a mechanism other than sodium and volume retention.

Adult↗
PubMed1988

Corticosteroid-induced stimulation of atrial natriuretic peptide in man.

UNLABELLED: Previously, we reported elevated plasma immunoreactive ANP (irANP) levels from the 2nd to the 9th day of administering either prednisone, 50 mg/day, or 9 alpha-fludrocortisone acetate (9 alpha F), 0.6 mg/day, to normal humans. To investigate the course of plasma irANP levels during the first 48 h of corticosteroid administration, 9 healthy men (mean age +/- SEM, 24 +/- 1 years) received in randomised sequence A) a 4-h iv infusion of prednisolone sodium tetrahydrophthalate followed by oral administration of prednisone for 2 days; or B) a 4-h infusion of aldosterone followed by oral administration of 9 alpha F for 2 days. Basal supine plasma irANP levels averaged 32 +/- 5 ng/l in study A and 30 +/- 6 ng/l in study B; they were unchanged or even deceased up to 24 h of glucocorticoid or mineralocorticoid administration, but rose (P less than 0.01) to 56 +/- 9 and 62 +/- 12 ng/l at 48 h, respectively, of the two interventions. During glucocorticoid treatment, blood pressure (BP) and indices of the sodium-fluid volume state were unchanged after 48 h. During 9 alpha F administration, body weight increased (1.1 +/- 0.3%, P less than 0.001), whereas urinary sodium excretion (63 +/- 7%, P less than 0.001), hematocrit (4.1 +/- 1.1%, P less than 0.001), and plasma renin activity (38 +/- 4%, P less than 0.001) decreased. CONCLUSIONS: The increase in circulating irANP at 48 h of administration of either a glucocorticoid or a mineralocorticoid demonstrates a distinct but slow response of the ANP system to these corticosteroids in normal humans.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Serum lipoproteins during treatment with antihypertensive drugs.

Hypertension and certain alterations in serum lipoproteins such as a decrease in high density lipoprotein-cholesterol (HDL-C), an increase in low density lipoprotein-cholesterol (LDL-C) and perhaps also elevated triglycerides (Tg), are complementary coronary risk factors. Moreover, it has become evident that several of the drugs used for standard antihypertensive therapy may also interact with lipoprotein metabolism. The following has been observed after 1 to 12 months of treatment. Various diuretics can significantly increase LDL-C and/or very LDL-C and total C/HDL-C ratio, while HDL-C is often largely unchanged; Tg also are often elevated. LDL-C increased in diuretic-treated men and in chlorthalidone-treated postmenopausal women but not in chlorthalidone-treated premenopausal women. The latter may be protected from this side effect. Drug dosages were usually high in these studies. Indapamide, given at a dose of 2.5 mg/day, seems to exert no relevant effect on the lipoproteins. It is not established whether this difference is related to the nature of the drugs or the doses used. There is little doubt that the dose of chlorthalidone used was greater than that required for a full antihypertensive effect of this drug. Several beta-blockers given as monotherapy induce significant increases in Tg and a tendency for decreases in HDL-C. These changes are most prominent on non-selective beta 1+2-blockers without partial intrinsic sympathomimetic activity (ISA), less pronounced on highly selective beta 1-blockers without ISA, and even more discrete or absent on beta-blockers with distinct ISA. Other sympatholytics such as reserpine, methyldopa, debrisoquine, urapidil, clonidine, labetalol, or postsynaptic alpha-blockers (prazosin, trimazosin, doxazosin etc.) did not affect or, postsynaptic alpha-blockers in particular, sometimes even slightly decreased Tg or LDL-C and very LDL-C values. During combination therapy, diuretic-induced increases in LDL-C were at short term prevented or reversed by the concomitant administration of certain beta-blockers, but not by sympatholytics such as reserpine, methyldopa or clonidine. With combined diuretic-prazosin treatment, a tendency for slightly higher HDL-C was reported. Angiotensin converting enzyme inhibitors (captopril, enalapril) and calcium channel blockers (verapamil, nifedipine, nitrendipine, diltiazem) seem to be largely devoid of undesirable effects on serum lipoproteins. Monotherapy with the potent direct vasodilator carprazidil improved blood pressure and significantly increased HDL-C. Whether and to what extent the observed variations in lipoproteins may persist beyond 1 year of treatment is as yet unclear.(ABSTRACT TRUNCATED AT 400 WORDS)

Antihypertensive Agents↗
PubMed1988

Dysregulation of blood pressure in normotensive offspring of hypertensive parents.

In normotensive humans with a positive family history of essential hypertension (FHH), blood pressure (BP) is often dysregulated. Resting BP already tends to be slightly higher than in age-matched control groups with negative FHH; BP responses to high sodium intake and perhaps to psychological and/or physical stress may also be exaggerated. Considering BP regulating factors, total exchangeable body sodium, whole blood volume, and their responses to low or high sodium intakes are normal in normotensive subjects with positive FHH; this does not exclude an existing although fully compensated regulatory disturbance. The response of plasma immunoreactive atrial natriuretic peptide levels to a high sodium intake seems to be impaired. On the other hand, a tendency for high ouabain-like Na+/K+-ATPase activity was reported in some normotensive subjects with positive FHH; data on central blood volume are lacking. Basal plasma renin, angiotensin II (AngII), and aldosterone levels, the reactivity of BP to acute increases in circulating AngII, and the responses of these variables to changes in sodium intake did not differe significantly between normotensive groups with a negative or positive FHH; this does not exclude a tendency for low renin-angiotensin activity in certain hypertension-prone families. The responsiveness of plasma aldosterone to acute rises in circulating AngII appeared to be largely unaltered when normotensive subjects with positive FHH were on moderate or high sodium intakes, but aldosterone responses may be blunted on a low sodium diet. Although a familial occurrence of subtle disturbances in AngII-dependent control of aldosterone and renal hemodynamics appears possible, BP regulation by the renin-angiotensin system is probably often intact at the stage of prehypertension. The finding of unaltered basal peripheral venous plasma norepinephrine (NE) and epinephrine levels and NE responses to changes in sodium intake, posture, or physical exercise in normotensive subjects with positive FHH has so far provided no evidence for enhanced sympathetic activity; nevertheless, direct analysis of regional nerve activity or NE release will be required to resolve this question. Regardless of the level of sympathetic activity, an exaggerated pressor responsiveness to NE occurs as a common disturbance in normotensive subjects with a positive FHH.(ABSTRACT TRUNCATED AT 400 WORDS)

Blood Pressure↗
PubMed1988

Potential pitfalls in the radioimmunoassay of physiological plasma levels of atrial natriuretic peptide.

Certain aspects of current radioimmunoassay methodology are presented which may restrict accurate measurement of physiological changes in circulating plasma levels of atrial natriuretic peptide. These include the method of sample collection and time of storage, sample extraction, concentration and reconstitution, the homogeneity of tracer and standards, separation of bound from free ligand and the assessment of blank values. If left unchecked, inaccuracies at each of these stages may cumulatively result in unreliable assessment of changes in circulating ANP levels and limit further understanding of its physiological role.

Atrial Natriuretic Factor↗
PubMed1988

[Pharmacologic effects of atrial natriuretic peptide in humans].

Since the discovery of atrial natriuretic peptide (ANP) by de Bold in 1981, several scientists (e.g. nephrologists, endocrinologists, cardiologists) have contributed to research efforts to define the physiologic and pharmacologic profile of the peptide. ANP given in pharmacologic doses seems to lower blood pressure, probably by reducing both preload and afterload. ANP increases renal water and electrolyte excretion, although the underlying mechanisms have not been entirely clarified yet. The depressor and natriuretic effect of ANP act in harmony with an inhibitory effect on the release of renin, aldosterone, and arginine-vasopressin. While the physiologic role or importance of ANP is still in question, synthetic alpha ANP has a promising pharmacologic profile in renal and cardiovascular pathologic states.

Atrial Natriuretic Factor↗
PubMed1988

Sodium and responses to infused noradrenaline and angiotensin II in subjects predisposed to hypertension.

A disturbed adrenergic dependent blood pressure regulation may represent a familial component in the pathogenesis of essential hypertension; its possible relation to sodium metabolism is presently unknown. Body sodium, the cardiovascular pressor reactivity to infused noradrenaline or angiotensin II, plasma levels of noradrenaline, adrenalin, renin, angiotensin II, aldosterone and atrial natriuretic peptide were measured on a low or high sodium diet in 10 normotensive young subjects without and 13 normotensive subjects with familial predisposition to hypertension. On the low sodium diet, the two groups did not differ significantly in the considered parameters, while blood pressure was slightly higher in predisposed subjects (+7/+7 mmHg). The change from the low to the high sodium diet was associated with a significant increase in supine systolic blood pressure in predisposed but not in non-predisposed subjects (P less than 0.05). Exchangeable sodium, body weight atrial natriuretic peptide and the pressor reactivity to infused adrenalin or angiotensin II increased significantly while plasma catecholamines, renin, angiotensin II and aldosterone levels were suppressed to a comparable extent in the two groups. The findings of this investigation confirm that sodium has an important regulatory effect on cardiovascular pressor responsiveness. The disturbed noradrenergic-dependent regulation of predisposed subjects is not explained by an abnormal adaptation of sympathetic dependent mechanisms or of other pressor factors to variations in dietary sodium intake.

Adult↗