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Biomedical subjects

P Weidmann

Publications and source records attributed to P Weidmann.

At least 127 records · Page 7Linked to original sources
PubMed1988

Blunted aldosterone responsiveness to angiotensin II in normotensive subjects with familial predisposition to essential hypertension.

The responsiveness of plasma aldosterone to an angiotensin (Ang) II infusion was assessed in normotensive young men, nine without and 13 with a family history of essential hypertension, after 7 days of low (mean urinary sodium 12 +/- 10 mmol/24 h) and 7 days of high (269 +/- 92 mmol/day) sodium intake. Under both conditions, the two study groups did not differ in body weight, arterial pressure, heart rate, plasma or urinary sodium and potassium or plasma renin, aldosterone or Ang II levels. However, after both dietary periods, the relationship between plasma aldosterone and plasma Ang II concentrations had shifted significantly (P less than 0.01) to the right in predisposed compared to non-predisposed subjects. The sodium-related changes in adrenocortical sensitivity to Ang II were similar in the two groups. The pressor response to Ang II did not differ between the two groups of subjects. These findings suggest that, in addition to the known cardiovascular abnormalities of sympathetic, renal and ion transport mechanisms, a fourth area of disturbance involving the response of plasma aldosterone to Ang II may be present in normotensive subjects with familial predisposition to essential hypertension.

Adrenal Cortex↗
PubMed1987

[History and physiology of atrial natriuretic peptides in man].

The recent discovery of the atrial natriuretic peptide (ANP) system and its possible physiological role in man are discussed. ANPs are produced in the atria of various species, including man. In normal humans the biologically active alpha-ANP, a peptide consisting of 28 amino acid residues, is released into the circulation through cleavage from a larger prohormone which is stored in specific granules in atrial myocytes. The secretion of alpha-ANP from the heart is activated during atrial distension secondary to volume overload or increased atrial pressures. When injected intravenously, synthetic human alpha-ANP can produce a wide spectrum of hemodynamic, endocrine and renal effects. The ANP system may well play an important role in the homeostasis of (central) blood volume and blood pressure.

Amino Acid Sequence↗
PubMed1987

Comparative effects of doxazosin and hydrochlorothiazide on serum lipids and blood pressure in essential hypertension.

The efficacy and safety of doxazosin (mean dosage 6.9 mg, range 1 to 16) in the treatment of essential hypertension were compared in a double-blind study with those of hydrochlorothiazide (HCTZ) (mean dosage, 84.6 mg, range 25 to 100) in 104 hypertensive patients treated once daily for 6 months. Thirty-five patients were also assessed for comparative effects of the 2 agents on serum lipid parameters. Doxazosin produced potentially favorable changes from baseline in the concentrations of serum lipid fractions (total triglycerides, total cholesterol, high density lipoprotein [HDL] cholesterol and the derived HDL/total cholesterol ratio) compared with HCTZ. The decreases in total triglyceride and total cholesterol concentrations and an increase in the HDL/total cholesterol ratio were significantly different (p less than 0.006) from the opposite changes observed with HCTZ. Clinically relevant decreases from baseline in supine and standing blood pressures at 24 hours after administration did not significantly differ between the 2 agents. The incidence and severity of side effects were similar for both drugs. Three patients receiving doxazosin and 6 receiving HCTZ were withdrawn due to drug-related clinical side effects including 2 patients receiving HCTZ who were withdrawn because of laboratory test abnormalities. Eight HCTZ- and 1 doxazosin-treated patients developed hypokalemia and 6 HCTZ-treated patients developed hyperuricemia. These findings indicate that doxazosin and HCTZ provide comparable antihypertensive efficacy after 6 months of treatment using a once-daily regimen, but doxazosin produces a beneficial effect on the serum lipid profile as well as fewer biochemical aberrations.

Adrenergic alpha-Antagonists↗
PubMed1987

Plasma and urinary catecholamines as related to renal function in man.

To assess the relationship between renal plasma flow (ERPF) or glomerular filtration rate (GFR) and the levels of norepinephrine (NE) or epinephrine (E) in plasma or urine in the presence of progressive degrees of non-oliguric renal functional impairment, these variables were assessed simultaneously in 18 normal subjects, 72 with parenchymal kidney disease and 14 with essential hypertension. ERPF and GFR were lower (P less than 0.01 to 0.001) in the groups with renal disease (mean +/- SD, 340 +/- 230 and 68 +/- 43 ml/min/1.73 m2, respectively) or essential hypertension (434 +/- 101 and 97 +/- 25 ml/min/1.73 m2) than normal subjects (597 +/- 133 and 118 +/- 14 ml/min/1.73 m2). Plasma and urinary NE and E did not differ significantly among groups and were unrelated with ERPF or GFR (range 4 to 160 ml/min/1.73 m2), except for reduced (P less than 0.001) urinary NE and E excretion in the presence of a GFR less than 20 ml/min. Subgroups with renal disease and a normal (N = 39) or high blood pressure (N = 33) also were comparable in their plasma and urinary NE and E, while ERPF and GFR tended to be lower in hypertensive patients. It is concluded that a chronic reduction in excretory kidney function may have no relevant impact on circulating levels of NE and E per se, although their urinary excretion falls distinctly at the stage of advanced renal failure. These aspects deserve consideration when pathogenetic or diagnostic studies of catecholamines are performed in normotensive or hypertensive patients with impaired kidney function.

Blood Pressure↗
PubMed1987

Plasma levels and dialysance of atrial natriuretic peptide in terminal renal failure.

Plasma immunoreactive atrial natriuretic peptide (irANP) levels, their chromatographic profile, relationship with hemodynamic variables, and responses to hemodialysis (HD) or postural changes were investigated in HD patients. Peripheral venous supine plasma irANP averaged 167 +/- 31 (+/- SEM) pg/ml in 12 normal subjects (age 63 +/- 2 yr). In 42 HD patients (mean age 65 +/- 1 yr), plasma irANP in peripheral arterio-venous fistulae was high (447 +/- 50 pg/ml, P less than 0.01) before HD and decreased (P less than 0.001) to 164 +/- 24 pg/ml after HD. The latter reduced body weight by -2.3 +/- 0.2 kg (P less than 0.001) and blood pressure from 139/77 +/- 4/2 to 126/73 +/- 4/2 mm Hg (P less than 0.01). Pre-dialysis plasma irANP in right atrium, pulmonary artery or avfistula correlated with pulmonary capillary wedge pressure (N = 10, r = 0.66 to 0.73; P less than 0.05); HD-induced changes in these variables were also correlated (r = 0.80 to 0.90; P less than 0.05 to less than 0.01). Compared with supine values, upright posture decreased plasma irANP in 12 normal subjects and 8 HD patients (-40 and -42%, respectively, P less than 0.01). IrANP clearance from plasma averaged 24 +/- 5 ml/min across the hemodialyzer (N = 6) and 46 +/- 3 ml/min across the hemofilter (N = 4). We conclude that in terminal renal failure, circulating irANP consists largely of alpha ANP, is often elevated before HD, decreases with the change from recumbency to standing, falls after removal of excess fluid, and may depend strongly on left atrial and pulmonary arterial pressures.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗
PubMed1987

Potassium and norepinephrine- or angiotensin-mediated pressor control in pre-hypertension.

Blood pressure (BP), plasma electrolytes, renin, aldosterone, angiotensin II (AII) or catecholamines, the chronotropic effects of intravenous isoproterenol, norepinephrine (NE) or AII, the pressor responses to NE or AII, and the relationship between plasma AII and aldosterone concentrations were studied before and after 10 days of dietary supplementation with potassium 100 mmol/day, in normotensive members of normotensive (N = 12) or hypertensive (N = 12) families, and 11 patients with borderline essential hypertension. Under control conditions, the pressor responsiveness to NE was significantly enhanced in normotensive with positive family history for hypertension and hypertensive subjects; the other variables were comparable in the groups. After potassium supplementation, plasma potassium, renin, aldosterone or AII, and the relationship between AII and aldosterone levels increased significantly, while body weight, plasma catecholamines, the chronotropic effects of isoproterenol, AII or NE, the pressor effects of AII and plasma clearance of AII or NE were unchanged in all groups. In normotensive members of hypertensive families and patients with hypertension, BP was decreased and the exaggerated pressor responsiveness to NE was normalized; these variables were not modified in normotensive members of normotensive families. These observations are consistent with a potassium-remediable disturbance in NE- but not AII-dependent regulation of BP in the pathogenesis of essential hypertension.

Adult↗
PubMed1987

Effects of posture and ageing on circulating atrial natriuretic peptide levels in man.

Possible influences of posture or age on plasma immunoreactive atrial natriuretic peptide (irANP) levels and potential correlates were assessed in 12 young (age +/- s.e.m. 24 +/- 1 year) and 12 elderly (63 +/- 8 year) healthy subjects on a liberal sodium intake. The groups did not differ significantly in their basal 24-h urinary sodium excretion (210 +/- 23 versus 180 +/- 15 mmol/l). However, plasma irANP was five- to ninefold higher in the elderly (P less than 0.05-0.01). Plasma irANP averaged 167 +/- 31 and 24 +/- 3 pg/ml in the elderly and young, respectively, during recumbency, fell (P less than 0.05) to 101 +/- 21 and 11 +/- 1 pg/ml, respectively, with upright posture, and rose (P less than 0.01) to 250 +/- 51 and 50 +/- 9 pg/ml, respectively, after intravenous (i.v.) loading with 0.9% saline (2.14 l in 3 h). Supine blood pressure (BP) and plasma norepinephrine tended to be higher while renin and aldosterone levels were lower (P less than 0.01) in the elderly; the three latter variables rose (P less than 0.001) with upright posture. These findings demonstrate that in normal humans, circulating irANP levels vary with posture and ageing. These changes may have potential physiological relevance and should be considered when interpreting plasma irANP levels in pathological conditions.

Adult↗
PubMed1987

Effects of calcium antagonists on glucose homeostasis and serum lipids in non-diabetic and diabetic subjects: a review.

Results from early in vitro experiments have led to the assumption that a deterioration in carbohydrate metabolism must be expected if diabetic patients are treated with calcium antagonists. In order to determine the truth of this assumption, we reviewed 74 publications reporting effects on glucose homeostasis from acute, short-term and long-term therapy with calcium antagonists in non-diabetic patients, and 35 papers and abstracts dealing with the same problem in diabetic patients. The analogous question concerning the influence of calcium antagonists on the serum lipid profile was pursued in 43 recent communications. Long-term studies in particular suggest that although minor transitory changes under special circumstances cannot be excluded, in all likelihood neither glucose nor lipid homeostases are unfavourably altered by current clinical dosages of calcium antagonists in non-diabetic subjects or in patients with diabetes mellitus. Therefore, the benefit of antihypertensive or anti-anginal treatment with these medications is not compromised by untoward metabolic cardiovascular risks.

Blood Glucose↗
PubMed1987

Cardiovascular and renal profile of acute peripheral dopamine1-receptor agonism with fenoldopam.

Whether the dopaminergic system may be involved in essential hypertension is of pathogenetic as well as therapeutic interest. Therefore, we investigated in eight hypertensive and 12 normal subjects cardiovascular, endocrine, and renal responses to fenoldopam, which has been characterized experimentally as an agonist of peripheral postsynaptic dopamine1 receptors. A single oral dose of fenoldopam, 100 mg, changed blood pressure (BP) in hypertensive subjects (from 163/103 to 147/76 mm Hg; p less than 0.01 for systolic and p less than 0.001 for diastolic BP) and normal subjects (from 121/81 to 123/65 mm Hg; p less than 0.001 for diastolic BP); percentage decreases in diastolic BP averaged -20 +/- 6 and -16 +/- 7%, respectively. Fenoldopam-induced effects on other variables were similar in the two groups. Heart rate rose (p less than 0.001) on average from 69 to 92 beats/min in hypertensive and from 64 to 84 beats/min in normal subjects. Effective renal plasma flow increased (from 552 to 765 and 634 to 937 ml/min/1.73 m2; p less than 0.01), while glomerular filtration rate tended to decrease (from 121 to 99 ml/min/1.73 m2 in the hypertensive and from 119 to 97 ml/min/1.73 m2; p less than 0.001 in the normal group). Fractional sodium clearance was elevated (from 2.8 to 5.2 and 1.7 to 3.8%; p less than 0.01), as was free water clearance (from -1.7 to 0.6 and -1.7 to 0.1 ml/min/1.73 m2; p less than 0.01). Potassium clearance was largely unchanged. Plasma renin activity increased about twofold (p less than 0.01 in normal subjects), and plasma aldosterone by 40% (NS). Plasma norepinephrine levels increased twofold to 2.5-fold (p less than 0.001), and urinary norepinephrine excretion fivefold to 10-fold (p less than 0.01). Fenoldopam-induced changes were not significantly modified by intravenous and/or oral pretreatment with the dopamine-receptor antagonist metoclopramide or the cyclooxygenase inhibitor indomethacin. These findings suggest that in humans, fenoldopam may acutely override the dopaminergic antagonism of metoclopramide given in clinical dosage and that its cardiovascular and renal effects are not prostaglandin-mediated. Although acute sympathetic stimulation may be partially antagonistic, the concomitant BP-lowering, renal vasodilating, and natriuretic actions of fenoldopam represent a desirable profile of a potential antihypertensive agent.

Administration, Oral↗
PubMed1987

Pressure dependence of atrial natriuretic peptide during norepinephrine infusion in humans.

The relative contribution of increased blood pressure (BP) or norepinephrine (NE), or both, to the stimulatory effect of an NE pressor infusion on circulating immunoreactive atrial natriuretic peptide (ANP) was evaluated in 10 healthy young men. They were studied during an infusion of NE, which was applied initially alone and then in combination with sodium nitroprusside. NE infusion rate was increased in four 30-minute intervals to a final dose of 200 ng/kg body weight per minute, leading to 12-fold higher plasma NE levels than were seen during control conditions. This increased mean BP (from a mean basal value of 94 +/- 3 to 119 +/- 4 [SEM] mm Hg; p less than 0.001) and plasma immunoreactive ANP (from 50 +/- 7 to 112 +/- 17 pg/ml; p less than 0.001), whereas heart rate decreased (p less than 0.001). The NE infusion was continued at the highest dose and an additional infusion of sodium nitroprusside was started to titrate mean BP in 30-minute intervals down to control values; a mean sodium nitroprusside dose of 0.95 micrograms/kg/min restored mean BP to 93 +/- 4 mm Hg (p less than 0.001), decreased plasma immunoreactive ANP to basal values (51 +/- 4 pg/ml; p less than 0.001), increased heart rate (p less than 0.001), and left plasma levels of NE largely unchanged. Plasma protein and hematocrit rose about 5 to 6% (p less than 0.001) during the NE infusion and then decreased about 3 to 4% (p less than 0.001 and p less than 0.01) when sodium nitroprusside was added.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Atrial natriuretic peptide protects against acute ischemic renal failure in the rat.

Because of its ability to increase glomerular filtration, antagonize the actions of vasoconstrictors, and produce vasodilation, alpha human atrial natriuretic peptide (alpha-hANP) was evaluated for its potentially beneficial effects in experimental ischemic renal failure induced by 45-60 min of renal artery occlusion in bilaterally or unilaterally renally intact Sprague-Dawley rats. After ischemia, a 4-h intrarenal infusion of alpha-hANP restored 14C-inulin clearances in bilaterally and unilaterally intact animals from 0.05 +/- 0.006 and 0.05 +/- 0.01 ml/min per 100 g to 0.314 +/- 0.04 and 0.25 +/- 0.01 ml/min per 100 g, respectively (P less than 0.001, n = 8), compared with normal values of 0.49 +/- 0.023 ml/min per 100 g. Histologically, there was a progressive decrease in medullary hyperemia and prevention of intratubular cell shedding and granulocyte margination as a result of the 4-h alpha-hANP infusion such that after 24 and 48 h the histological appearance of the tissue was essentially normal. The results show that a 4-h intrarenal infusion of alpha-hANP after renal ischemia can preserve glomerular filtration rate and reduce renal tissue damage.

Acute Kidney Injury↗
PubMed1986

[Hypertension management in practice, 1986].

Persons with persisting (at least 3 measurements over several weeks) borderline blood pressure elevation or established hypertension should always be instructed to follow general non-pharmacological measures. Antihypertensive pharmacotherapy is recommended in the following situations: in hypertensive emergencies, immediately; if the hypertension is not due to a surgically remediable cause, in patients with documented (at least 3 measurements) blood pressure elevation to diastolic values greater than 100 mm Hg; in patients with "mild" hypertension (diastolic up to 104 mm Hg) which does not decrease to less than 160/95 mm Hg following 3 to 6 months of treatment with general non-pharmacological measures; in persons with borderline blood pressure values (141-159/91-94 mm Hg) that persist following 6 to 12 months of general measures and only if they have severe additional cardiovascular risk factors; in patients with pronounced isolated systolic hypertension (greater than 180 mm Hg). In elderly patients who are frail or have evidence of advanced cardiovascular disease, dementia or other debilitating illnesses, blood pressure-lowering drugs should generally be reserved for diastolic blood pressure values consistently exceeding 110 mm Hg. There have recently been important new developments in antihypertensive pharmacotherapy. Two new pharmacological principles, the calcium entry blockers and angiotensin converting enzyme (ACE) inhibitors, have been introduced widely into practical hypertension treatment. On the other hand, concern has arisen that the conventional, thiazide-diuretic based therapy, despite its established beneficial influence on blood pressure and most cardiovascular complications, may not significantly improve or may sometimes even adversely affect coronary prognosis because of metabolic side effects.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenergic beta-Antagonists↗
PubMed1986

Autonomic function tests as related to age and gender in normal man.

To obtain a comparative assessment of 5 different clinical autonomic function tests as related to age and gender in normal man, the beat-to-beat variation during deep breathing (BBV), orthostatic 30/15 R-R ratio, heart rate response to the Valsalva manoeuvre, blood pressure response to sustained handgrip and orthostatic blood pressure response were evaluated in 120 healthy subjects (60 women and 60 men) aged 22 to 92 yrs. Each of the functional parameters depending on cardiac parasympathetic integrity, i.e. the beat-to-beat variation, orthostatic 30/15 R-R ratio and Valsalva ratio, decreased (P less than 0.0001) progressively with increasing age. The blood pressure response to handgrip, which depends on the efferent sympathetic function, was unchanged, while the orthostatic response of systolic blood pressure, which depends on the function of the entire reflex arch, was augmented only minimally (P less than 0.001) with increasing age. No significant dependence on gender was noted, although blood pressure responses to handgrip tended to be slightly greater in men than women. Beat-to-beat variation expressed as the standard deviation of the mean R-R interval correlated with mean heart rate (P less than 0.05), while the coefficient of variation and the exspiration/inspiration ratio of beat-to-beat variation did not. The orthostatic 30/15 R-R ratio and beat-to-beat variation tended to be more closely interrelated (r = 0.56 to 0.63) than any of these tests with the Valsalva ratio (r = 0.51). The findings indicate that consideration of age may improve the diagnostic value of the orthostatic 30/15 R-R ratio.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Cardiovascular regulation during administration of co-dergocrine to normal subjects.

Whether and to what extent activation of peripheral presynaptic dopamine2-receptors may modulate the release of norepinephrine (NE) and so affect blood pressure (BP) in normal or hypertensive man is not clear. The hydrogenated ergotoxine derivative, co-dergocrine, given in effective antihypertensive rather than excessive experimental doses, has recently been shown to act predominantly as a peripheral dopamine2-receptor agonist in several species. Accordingly, BP regulation assessed has been in 8 normal men on placebo and after 3 weeks on codergocrine 4 mg/day. Co-dergocrine significantly reduced urinary NE excretion from 43 to 33 micrograms/24 h, supine and upright plasma NE 21 to 16 and 49 to 36 ng/dl, respectively, heart rate (-8 and -5%, respectively) and upright systolic BP, 115 to 102 mm Hg; upright diastolic BP also tended to be lower. A standard pressor dose of infused NE was lowered from 131 to 102 ng/kg/min, and the relationship between NE-induced changes in BP and concomitant NE infusion rate or plasma NE concentration was displaced to the left. Exchangeable sodium and plasma volume tended to be slightly decreased. Plasma and urinary electrolytes and epinephrine, plasma renin activity and aldosterone levels, pressor responsiveness to angiotensin II, the chronotropic responses to isoproterenol, and the NE-induced rise in BP, plasma clearance of NE, glomerular filtration rate and effective renal plasma flow were not consistently modified. The findings are consistent with effective peripheral dopamine2-receptor agonism by co-dergocrine in humans. Peripheral presynaptic dopaminergic activation may modulate sympathetic activity and BP in normal man.

Adult↗
PubMed1986

Alpha-1-adrenergic blockade and lipoprotein metabolism in essential hypertension.

The effect of the selective alpha 1-antagonist terazosin on serum lipoproteins and certain blood pressure-regulating factors was assessed in 15 patients with essential hypertension. Terazosin given during 8 weeks reduced arterial pressure (from 153/103 +/- 3/2 (SE) to 143/96 +/- 5/2 mm Hg; P less than 0.02) but did not modify body weight, heart rate, blood volume, plasma renin activity, aldosterone and catecholamine levels, or serum cholesterol, triglycerides, and their lipoprotein fractions. In nine of the patients, blood pressure control was not achieved with terazosin monotherapy and the diuretic methyclothiazide, 2.5 mg, was added. After 8 weeks of combined treatment, blood pressure decreased further (P less than 0.05); serum lipids and lipoprotein fractions did not change as compared with placebo or terazosin conditions. These findings indicate that terazosin in monotherapy does not unfavorably influence lipid metabolism.

Adrenergic alpha-Antagonists↗
PubMed1986

Blood pressure control in normotensive members of hypertensive families.

The cardiovascular pressor responses to a stepwise increase in plasma norepinephrine or angiotensin II concentrations, induced by infusions, were studied in 23 normotensive subjects with a negative and 25 with a positive family history of essential hypertension. The two study groups had a similar mean age (24 +/- 2 (SD) yr), body weight, blood pressure (112/64 +/- 10/7 mmHg), heart rate, plasma and urinary sodium and potassium, and plasma norepinephrine, epinephrine, angiotensin II, renin and aldosterone levels. However, subjects with positive history differed from those with negative history of hypertension by a decreased pressor dose of infused norepinephrine (89 +/- 29 vs. 135 +/- 66 ng/kg/min; P less than 0.005), and a significant (P less than 0.01) shift to the left of the relationship between norepinephrine-induced changes in mean arterial pressure and concomitant changes in plasma norepinephrine. In contrast, the relation between stepwise increasing plasma angiotensin II levels and induced changes in diastolic blood pressure or plasma aldosterone did not differ significantly between the two study groups. These findings delineate a distinct abnormality which may often occur in normotensive offspring of hypertensive families. It is characterized by a selectively disturbed noradrenergic blood pressure control in the presence of a normal angiotensin-mediated blood pressure and aldosterone regulation.

Adult↗