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Biomedical subjects

F B Müller

Publications and source records attributed to F B Müller.

At least 37 records · Page 2Linked to original sources
PubMed1989

Mechanisms of action and clinical use of calcium antagonists in hypertension.

Calcium antagonists are potent arterial vasodilators that do not lead to relevant chronic sympathetic reflex activation and sodium and volume retention. This favorable hemodynamic profile renders them suitable for monotherapy of hypertension in which they can reduce the calcium influx-dependent functional component of elevated vascular resistance that may be enhanced by altered vascular muscle cation handling and increased intracellular free calcium concentrations. Clinical studies have proved their efficacy, safety, and good tolerability alone or in combination with other drugs in uncomplicated hypertension in which they are particularly effective in older, low renin, and possibly, black patients. These properties and their efficacy in the treatment of severe and accelerated hypertension or hypertensive emergencies make them a valuable addition to already available drug therapy.

Animals↗
PubMed1988

Hemodynamic and counterregulatory effects of calcium antagonists in hypertension.

Increased systemic vascular resistance in essential hypertension depends on increased calcium influx. Calcium antagonists lower cytosolic free calcium concentrations mainly through a reduction of transmembraneous calcium influx and are potent arterial vasodilators. Dihydropyridine calcium antagonists are pharmacologically more potent with respect to arterial vasodilatation than verapamil- or diltiazem-type calcium antagonists and have less or no clinically detectable negative inotropic effects, but this seems to be of importance only in patients with reduced cardiac function. All calcium antagonists lower high blood pressure through a reduction of elevated systemic vascular resistance without clinically relevant activation of sympathetic reflexes or the renin-angiotensin-aldosteron system. However, subtle changes of sympathetic nervous system activity may codetermine the acute and chronic blood pressure response. They do not lead to volume retention because of improved intrarenal hemodynamics and a diuretic effect. Interference with angiotensin and sympathetically mediated vasoconstrictor mechanisms probably also contributes to their antihypertensive effect. This hemodynamic profile is similar for all calcium antagonists but the degree of acute sympathetic stimulation seems to be greater for dihydropyridines. Their overall favorable hemodynamic and neurohumoral profile and their proven efficacy and lack of serious side effects have made calcium antagonists a valuable addition to the armanentarium available for monotherapy of hypertension.

Animals↗
PubMed1988

Wideband external pulse recording during cuff deflation: a new technique for evaluation of the arterial pressure pulse and measurement of blood pressure.

Analysis of the external brachial pulse recorded during standard blood pressure cuff deflation with use of a transducer with a wide frequency response has revealed a reproducible pattern with three distinct components that we have labeled K1, K2, and K3. K1 is a low-amplitude, low-frequency signal that is present with cuff pressures above systolic pressure. K2 is a triphasic signal appearing at systolic pressure and disappearing at diastolic pressure, which approximately corresponds to the audible Korotkoff sound. K3 appears with cuff pressure between systolic and diastolic pressure and continues to be present below diastolic pressure. Intra-arterial pressure recordings made with a high-fidelity Millar catheter-tip manometer revealed K2 and K3 analogs. K3 resembles the intra-arterial pressure waveform and when calibrated according to the pulse pressure, noninvasive dK3/dt determinations correlated well with intra-arterial dP/dt measurements. The appearance/disappearance property of K2 was designated as the "K2 algorithm" and represents a new, objective noninvasive method for measurement of blood pressure. The K2 algorithm compares favorably with intra-arterial measurements, is more accurate than the auscultatory technique, and may be especially useful in clinical situations in which the auscultatory technique does not work well.

Adolescent↗
PubMed1988

Suppressed aggression and hyperdynamic cardiovascular regulation in normotensive offspring of essential hypertensive parents.

To trace a possible association between suppressed aggression and enhanced responses of the cardiovascular system and plasma catecholamines in a "prehypertensive" state, two groups of 24 subjects with either normal blood pressure and no family history of hypertension or normal blood pressure and a positive family history of hypertension were matched for sex and age (18-24 years). Suppressed aggression was defined by the Rosenzweig Picture-Frustration test, a projective assessment of reactions to everyday stress. Before, during, as well as after application of mental stressors (Stroop color-word conflict test and mental arithmetic), the responses of blood pressure, heart rate, and venous plasma catecholamines were measured. Offspring of hypertensive parents with suppressed aggression (n = 10) had significantly higher heart rates and diastolic blood pressures than offspring of hypertensive parents without suppressed aggression (n = 14), using analyses of covariance for repeated measures to eliminate the influence of anxiety. Plasma norepinephrine responses tended to be greater in the offspring with suppressed aggression. The results suggest that in normotensive offspring of hypertensive parents, a behavioral pattern with suppressed aggression promotes a hyperdynamic cardiovascular state and enhances the hypertensive developmental process.

Adolescent↗
PubMed1987

Calcium antagonist induced vasodilation in peripheral, coronary and cerebral vasculature as important factors in the treatment of elderly hypertensives.

Increased arteriolar tone is the pathophysiological hallmark of essential hypertension and is determined by the intracellular free calcium concentration in the vascular smooth muscle cell. Calcium influx is an important determinant of vasoconstriction and excess calcium influx-dependent vasoconstriction has been shown by plethysmographical studies in patients with essential hypertension. Calcium antagonists acutely lower BP by reducing calcium influx, calcium concentration and peripheral resistance. The degree of the attendant sympathetic nerve reflex activation and counter-regulatory mechanisms determines the antihypertensive response of the individual. Chronic monotherapy with a calcium antagonist results in an antihypertensive response, which is directly related to the patient's age and pretreatment BP and indirectly related to plasma renin levels. The resulting reduction in after-load neither leads to reduced cerebral blood flow in hypertensive patients, nor aggravates congestive heart failure. Calcium antagonists are a useful alternative to diuretics, primarily in older patients with low renin levels, either alone or combined with any other antihypertensive drug, and provide effective and safe control of blood pressure.

Aged↗
PubMed1987

The vasodilator potency of atrial natriuretic peptide in man.

The vasodilating potency of alpha-human atrial natriuretic peptide (alpha-hANP) was investigated in the forearms of 16 normotensive subjects, 22 to 48 (mean 28) years old, with the use of venous occlusion plethysmography. alpha-hANP, 0.005 to 1.5 micrograms/min/100 ml forearm volume (FAV), infused in nine dose steps into the brachial artery increased forearm blood flow (FAF; ml/min/100 ml FAV) from 2.8 +/- 0.4 (SEM) to a maximum of 9.6 +/- 1.1. Forearm vascular resistance (mean arterial pressure/FAF) decreased by 72%. The alpha-hANP dose that produced a 50% vasodilator response was 0.093 +/- 0.016 microgram/min/100 ml FAV (n = 11) and it resulted in a venous plasma concentration of ANP (pANP) of 115 +/- 7 pmol/liter (normal 2 to 80; radioreceptor assay). Intraindividually, the maximum dose of alpha-hANP induced an increase in FAF that was 60% of the maximum response to sodium nitroprusside (14.1 +/- 1.8). Combined infusions (n = 9) of maximum forearm vasodilator doses of alpha-hANP and nitroprusside increased FAF to 22.7 +/- 3.4; this additive vasodilator effect of alpha-hANP and nitroprusside is consistent with their different actions on the guanylate cyclase system. In man, the direct vasorelaxant effect of alpha-hANP occurs at concentrations within the upper normal range of pANP, suggesting a physiologic vasodilator role for alpha-hANP.

Adult↗
PubMed1987

Greater vasodilator responsiveness to atrial natriuretic peptide in low-renin essential hypertensives.

Forearm vasodilator responses to atrial natriuretic peptide (ANP) were studied in twelve untreated patients with essential hypertension and twelve normotensive subjects. Alpha-human ANP (0.005 to 1.5 micrograms/min per 100 ml forearm volume) infused into the brachial artery increased forearm blood flow dose-dependently. This was paralleled by a decrease in forearm vascular resistance (FVR) which, at lower doses, was greater in essential hypertensives than in normotensives (P less than 0.001), and showed a lower ED50 for ANP in essential hypertensives (P less than 0.01). At higher doses of ANP the difference in vasodilator response between hypertension and normotension disappeared; the response to ANP was associated with a fall (P less than 0.01) in systemic blood pressure in hypertensives but not normotensives. At lower doses, the decreases in FVR were correlated directly with plasma renin activity in hypertensives (r = 0.656; P less than 0.05) but not normotensives. These data suggest greater vasodilator responsiveness to infusions of low doses of ANP in essential hypertensives, which is greater in low-renin states and blunted in high-renin states.

Adult↗
PubMed1986

Calcium antagonists and the second drug for hypertensive therapy.

Calcium antagonist monotherapy is more effective in older patients and in those with low plasma renin activity, whereas beta blockers control blood pressure better in younger patients and in those with normal or high renin activity. Monotherapy with a calcium antagonist has been shown to result in the reduction of diastolic blood pressure to equal to or less than 95 mm Hg in more than 80 percent of patients with essential hypertension. We investigated the antihypertensive efficacy of verapamil plus an angiotensin converting enzyme inhibitor and nifedipine plus a beta blocker in 24 patients (aged 41 to 68) with moderate to severe hypertension in whom monotherapy with a calcium antagonist had been ineffective. Blood pressure recorded in patients during the placebo period was 175 +/- 3/111 +/- 2 mm Hg (mean +/- SEM). Twelve patients received monotherapy with nifedipine (50.0 +/- 5.2 mg per day) and 12 others received verapamil (460 +/- 20 mg per day); neither treatment resulted in the reduction of diastolic blood pressure to less than 90 mm Hg. However, this goal was achieved when atenolol (89.5 +/- 25.7 mg per day) was added to the regimen of patients receiving nifedipine and enalapril (29.5 +/- 5.0 mg per day) was added to the regimen of those receiving verapamil; resultant blood pressures were 127 +/- 3/83 +/- 2 mm Hg and 137 +/- 5/85 +/- 1 mm Hg, respectively. It is suggested that in patients in whom hypertension is inadequately controlled by calcium antagonist monotherapy, counter-regulatory mechanisms can be blocked by the addition of a beta blocker or an angiotensin converting enzyme inhibitor to the calcium antagonist regimen, resulting in greatly improved, simple, well-tolerated, and safe control of blood pressure.

Adrenergic beta-Antagonists↗
PubMed1986

[Secretion of atrial natriuretic peptide: relation to atrial pressure and systemic blood pressure].

To determine the influence of atrial pressure, heart rate and loss of atrial-ventricular synchrony in the release of atrial natriuretic peptide (ANP), plasma ANP concentrations were measured by radio-receptor assay in 12 patients during diagnostic cardiac catheterization and in patients with atrial fibrillation and during cardiac pacing. There was a relationship between right atrial pressure and right atrial ANP concentration (r = 0.813, p less than 0.01). Acute loss of atrial-ventricular pacing mode induced an increase in plasma ANP concentration from 44 +/- 8 to 104 +/- 13 pmol/l (n = 11, p less than 0.01) provided that systemic blood pressure was maintained. In contrast, if hypotension developed during ventricular pacing, the ANP levels fell from 68 +/- 11 to 14 +/- 7 pmol/l (n = 5, p less than 0.05) within five minutes despite elevation of atrial pressure. We therefore conclude that atrial pressure and the loss of atrioventricular synchrony may profoundly alter ANP release. The fall in plasma ANP concentration in acute hypotension suggests that, in addition to atrial pressure, ANP release is controlled by a peripheral negative feedback mechanism.

Aged↗
PubMed1986

Atrial natriuretic peptide and atrial pressure in patients with congestive heart failure.

To define the relation between atrial pressures and the release of atrial natriuretic peptide, we measured plasma concentrations of the peptide in 26 patients with cardiac disease--11 with normal atrial pressures and 15 with elevated atrial pressures (11 of these 15 had elevated pressures in both atria). Mean peptide levels (+/- SEM) in the peripheral venous blood were increased in the 11 patients with cardiac disease and normal atrial pressures, as compared with 60 healthy controls (48 +/- 14 vs. 17 +/- 2 pmol per liter). In the patients with elevated atrial pressures, peptide concentrations were increased twofold in peripheral venous, right atrial, pulmonary arterial, and systemic arterial plasma, as compared with the concentrations in the patients with normal atrial pressures. A step-up in peptide concentration was seen between the venous and right atrial plasma (P less than 0.002) and between the pulmonary and systemic arterial plasma (P less than 0.01), suggesting release of the peptide from the atria. A linear relation was found between right atrial pressure and right atrial peptide concentration (r = 0.835, P less than 0.001) and between pulmonary wedge pressure and the systemic arterial peptide concentration (r = 0.866, P less than 0.001). Right atrial pressure and the peptide concentration both increased with exercise testing in the nine patients evaluated. We conclude that the release of atrial natriuretic peptide is at least partly regulated by right and left atrial pressures. Distinguishing the relative contributions of the two atria and defining the role of peptide release in the pathogenesis of heart failure will require further investigation.

Adult↗
PubMed1986

Calcium antagonism--a new concept for treating essential hypertension.

Research on calcium antagonists has been prompted by the observation that the powerful vasodilatory effect of verapamil, as well as other calcium antagonists, is enhanced in hypertensive patients. Increased vascular resistance, seen in most types of hypertension, is determined by the intracellular free calcium concentration. The finding of an increased vascular responsiveness to calcium-channel blockade and the direct relation between the degree of antihypertensive response and the height of pretreatment blood pressure indicate abnormal intracellular calcium handling in patients with essential hypertension. This is supported by the observation that the intracellular free calcium concentration was significantly increased in patients with essential hypertension compared with normotensive subjects. The decrease in blood pressure with calcium antagonists was directly correlated with the patient's age and inversely with the pretreatment plasma renin activity. There was comparable antihypertensive efficacy among verapamil, nifedipine and nitrendipine. Increased understanding of pathophysiologic mechanisms in essential hypertension and pharmacotherapeutic studies have led to a new strategy for treatment of high blood pressure--in which calcium antagonists may be used, at least in part, as alternatives to diuretic drugs primarily in older and low renin patients with essential hypertension.

Age Factors↗
PubMed1986

Regional blood flow and neurohormonal responses to milrinone in congestive heart failure.

We measured systemic hemodynamics, regional blood flow, and neurohormonal parameters in 13 patients with severe chronic congestive heart failure before and after 1 month of therapy with oral milrinone, a bipyridine cardiotonic agent. After milrinone there were significant reductions in pulmonary wedge pressure (27 +/- 2 to 19 +/- 3 mm Hg; P less than 0.02) and systemic vascular resistance (1866 +/- 152 to 1393 +/- 93 dyne X sec/cm5; P less than 0.05) that were associated with increases in cardiac index (1.85 +/- 0.15 to 2.47 +/- 0.20 L/min/m2; P less than 0.02). There was a marked improvement in forearm blood flow (1.98 +/- 0.14 to 3.02 +/- 0.16 ml/min/dl; P less than 0.01) and a reduction in forearm vascular resistance (45 +/- 3 to 30 +/- 3 U; P less than 0.01). Overall there was no significant change in renal blow flow, renal vascular resistance, or glomerular filtration rate. However, there was a heterogeneous response of renal blood flow and glomerular filtration rate, such that both were directly correlated with the magnitude of increase of cardiac index (r = 0.587 [P less than 0.05] and r = 0.721 [P less than 0.01], respectively). After milrinone there were no significant overall or subgroup changes in urinary sodium excretion, blood volume, plasma renin activity, urinary aldosterone levels, plasma or platelet vasopressin levels, or plasma norepinephrine levels. Thus 1 month of therapy with milrinone improves systemic and forearm hemodynamics, but its effects on renal blood flow and function were heterogeneous. These heterogeneous effects on regional blood flow may depend on the relative vasodilator and inotropic effects of milrinone.

Aged↗
PubMed1986

Cardiac and vascular beta-adrenoceptor-mediated responses before and during treatment with bisoprolol or atenolol.

The degree of cardiac and vascular beta-adrenoceptor blockade of bisoprolol and atenolol was determined by the chronotropic dose 25 (CD25) of isoproterenol (the dose of an intravenous isoproterenol bolus required to increase resting heart rate by 25 beats/min) and by the increase in forearm blood flow (venous occlusion plethysmography) to intrabrachial artery infusions of increasing doses of isoproterenol (0.12, 1.2, 4, 12, and 20 ng/min/100 ml forearm tissue). Measurements were taken following placebo and after one week's treatment with atenolol or bisoprolol under double-blind conditions using a within-patient crossover design. Two patients received 10 mg bisoprolol and 50 mg atenolol daily, and three patients 20 and 100 mg daily, respectively. Both beta-blockers produced a similar fall in blood pressure, heart rate, and plasma renin activity. While CD25 of isoproterenol was comparable for both drugs, forearm blood flow to intra-arterial infusion of isoproterenol increased to a greater extent following bisoprolol (20 mg) than during atenolol (100 mg) treatment. Equieffective cardiac beta-blockade with bisoprolol and atenolol was associated with a lesser degree of vascular beta-adrenoceptor blockade during treatment with the more cardioselective beta-blocker bisoprolol.

Adrenergic beta-Antagonists↗
PubMed1986

Abnormal cellular calcium regulation in essential hypertension.

The plasticity of cellular Ca2+ control and the events regulated by [Ca2+]i and other messengers make it difficult to assign causative or consequential roles to deranged platelet Ca2+-linked processes in the pathophysiology of essential hypertension. Our studies in human platelets support an underlying membrane pathology as being causative since observed derangements including partial membrane depolarization and enhanced calcium influx, enhanced hormone responsiveness and coupling to adenylate cyclase, increased phosphoinositide metabolism, as well as stimulated Ca2+-ATPase extrusion activity are membrane associated systems. Modification of phosphoinositide metabolism may be a key factor accounting for the multifaceted membrane abnormalities and eventually contribute to the elevated cytosolic [Ca2+]i concentration in essential hypertension. Whether these membrane abnormalities can also be found in human smooth muscle cells has yet to be determined.

Blood Platelets↗
PubMed1986

Hyperadrenergic borderline hypertension is characterized by suppressed aggression.

The effect of suppressed aggression on the reactivity of the sympathetic nervous and cardiovascular systems has been investigated in two groups of 24 subjects each with either borderline hypertension or normal blood pressure and no family history of hypertension. Groups were matched for sex and age (18-24 years). Suppressed aggression was defined by the newly standardized Rosenzweig Picture-Frustration test, a projective method assessing the reaction to everyday stress. Responses of blood pressure, heart rate, and venous plasma catecholamines were measured before and during application of mental stressors, using the Stroop color-word conflict test and mental arithmetic. In an analysis of covariance for repeated measures, which eliminates the influence of anxiety, borderline hypertensive subjects with suppressed aggression had significantly higher heart rates and diastolic blood pressures and a greater noradrenaline reactivity than borderline hypertensive subjects without suppressed aggression or normotensive subjects. Suppressed aggression may lead to a hyperadrenergic form of early borderline hypertension and thereby contribute to higher blood pressure.

Adolescent↗
PubMed1986

Withdrawal of the long-acting beta blocker bopindolol is not associated with beta-adrenoceptor supersensitivity.

beta-Adrenoceptor sensitivity after abrupt withdrawal of long-term therapy (5-12 months) with bopindolol (1-2 mg/day), a long-acting beta-adrenoceptor blocking agent with intrinsic sympathomimetic activity, was assessed in five patients with uncomplicated essential hypertension. The chronotropic dose 25 of isoproterenol (CD 25), plasma concentrations of catecholamines, triiodothyronine and thyroxin, plasma renin activity and aldosterone, hemoglobin, hematocrit and oxyhemoglobin dissociation were measured on the last day of bopindolol administration and 1, 2, 3, 6, and 13 days after abrupt replacement by placebo tablets. The chronotropic dose 25 of isoproterenol (microgram/m2) was greater than 25.6 in all patients on the last day of bopindolol therapy. On day 1 in patients who had been taking 2 mg/day of bopindolol, CD 25 remained greater than 25.6 but fell to 12.1 in the one patient who had been taking 1 mg/day. On day 2, CD 25 was 10.19 +/- 2.97 and felt gradually to the lowest value of 3.76 +/- 1.19 on day 13. Throughout the study, plasma concentrations of catecholamines, triiodothyronine and thyroxin, and oxyhemoglobin dissociation remained unchanged. Plasma renin activity and plasma aldosterone, which were suppressed during bopindolol therapy, rose during placebo, coinciding with a fall in hemoglobin and hematocrit. No subjective symptoms of increased beta-adrenoceptor-mediated functions were reported by the patients throughout the whole study period. Therefore, hypersensitivity of beta-adrenoceptor-mediated responses was not demonstrated within the first 13 days after sudden withdrawal of bopindolol.

Adrenergic beta-Antagonists↗