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Biomedical subjects

F B Müller

Publications and source records attributed to F B Müller.

At least 55 records · Page 3Linked to original sources
PubMed1986

Once a day verapamil in essential hypertension.

Pharmacodynamic and therapeutic studies with a new slow release 240 mg verapamil formulation were performed in a total of 73 patients with essential hypertension (WHO I-II, diastolic greater than or equal to 100 mm Hg). Chronic administration of slow release 240 mg verapamil, one or two tablets in the morning, resulted in 24 h plasma concentration profiles with trough levels greater than 40 ng ml-1 in 14 of 16 patients and good 24 h blood pressure control. There was no correlation between plasma verapamil or norverapamil concentration and blood pressure response. Monotherapy with slow release verapamil was well tolerated and resulted in good blood pressure control (less than or equal to 95 mm Hg diastolic) in 46 of the 57 patients. Responses were best in older patients and those with low plasma renin or higher control blood pressure. Slow release 240 mg verapamil given once daily is a simple and effective regimen.

Adult↗
PubMed1986

Differing hemodynamic responses to atrial natriuretic factor in two models of hypertension.

Hemodynamic responses to synthetic atrial natriuretic factor (ANF), were studied in renin-dependent two-kidney, one-clip (2K,1C) and deoxycorticosterone (DOC) salt-treated hypertensive rats as well as normotensive controls. ANF infusion (800 pmol/kg prime, 120 pmol X kg-1 X min-1 for 60 min) decreased blood pressure (BP) more in conscious 2K,1C (-24 +/- 4%) than in DOC salt-treated (-12 +/- 4%, P less than 0.05) or control rats. Hemodynamic parameters were also evaluated during graded infusion of three doses, each for 30 min. At 24 and 120 pmol X kg-1 X min-1, ANF lowered BP in 2K,1C rats, both conscious (from 156 +/- 6 to 144 +/- 7, P less than 0.05 and 135 +/- 5 mmHg, P less than 0.05) and anesthetized (from 148 +/- 7 to 138 +/- 7, P less than 0.05 and 128 +/- 7, P less than 0.05). In anesthetized 2K,1C, BP changes were associated with reduction in total peripheral resistance (TPR) that became significant at 120 pmol X kg-1 X min-1 (-10 +/- 2%), whereas cardiac output (CO) and stroke volume (SV) were unchanged. In DOC-salt-treated rats these doses did not lower BP despite progressive falls in CO (-7 +/- 3% and -24 +/- 5%, P less than 0.05) and SV (-8 +/- 2% and -23 +/- 5%, P less than 0.05), which were balanced by a simultaneous rise in TPR (+12 +/- 4% and +26 +/- 10%, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Identification of the direct vasodilator effect of milrinone with an isolated limb preparation in patients with chronic congestive heart failure.

We developed an isolated limb preparation to evaluate the direct vasoactive properties of cardioactive drugs on the forearm vasculature in patients with congestive heart failure. Using this model, we infused milrinone in subsystemic doses (1, 10, and 20 micrograms/min per 100 ml forearm volume [FAV] ) into the brachial artery of 13 patients with moderate-to-severe congestive heart failure. We monitored forearm hemodynamics, systemic hemodynamics, and milrinone plasma concentration from both the forearm venous effluent and pulmonary artery. This preparation enabled us to assess the direct forearm vascular response to milrinone. Compared with baseline forearm blood flow (2.46 +/- 1.37 ml/min/100 ml FAV), the three doses of milrinone resulted in increases in forearm blood flow to 2.66 +/- 1.43, 4.21 +/- 1.79, and 6.73 +/- 3.69 ml/min/100 ml FAV. This was associated with a reduction of forearm vascular resistance from the baseline value of 52 +/- 38 U to 47 +/- 36, 25 +/- 13, and 17 +/- 10 U. The p value for the difference in response of flow and resistance after the 10 and 20 micrograms doses vs that at baseline was .05. This forearm vasodilatation occurred without change in systemic hemodynamics or therapeutic milrinone plasma concentrations in the pulmonary artery. In five patients, we compared the response to intra-arterial milrinone with that of nitroprusside. At a dose of 10 micrograms/min/100 ml FAV, the response to nitroprusside (7.20 +/- 3.24 ml/min/100 ml FAV) was greater than that to milrinone (4.65 +/- 2.18 ml/min/100 ml FAV) (p less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Exercise hemodynamics and oxygen delivery in human hypertension. Response to verapamil.

To characterize the hemodynamic response to exercise and the effects of calcium channel antagonism in hypertensive subjects, invasive exercise hemodynamics were performed in the baseline state after intravenous infusion of verapamil and after 5 to 7 days of oral verapamil in 10 subjects with moderate to severe hypertension. We also assessed oxygen delivery and use and the response of the sympathetic nervous system by measuring plasma norepinephrine levels at rest and during exercise. Both routes of administration were associated with significant reductions of mean arterial pressure and systemic vascular resistance at rest and peak exercise (p less than 0.05). Changes in heart rate were not statistically significant. Following oral administration of verapamil, stroke volume increased significantly in both the resting and exercise states. Pulmonary wedge pressure did not increase; in fact, the Frank-Starling relationship of cardiac performance actually was improved. Oxygen delivery and use were unchanged with both routes of administration. There was no significant difference in rest and exercise plasma norepinephrine levels following verapamil therapy. Thus, verapamil resulted in a significant reduction of mean arterial pressure, mediated by a significant reduction of systemic vascular resistance, following both intravenous and short-term oral administration. This reduction occurred without expression of left ventricular dysfunction and was not at the expense of increased oxygen use or enhanced sympathetic nervous systemic activity.

Adult↗
PubMed1986

Calcium-regulating hormones in essential hypertension. Relation to plasma renin activity and sodium metabolism.

Circulating levels of the calcium-regulating hormones, calcitonin, calcitriol, and parathyroid hormone, were analyzed in relation to plasma renin activity in 10 persons with normal blood pressure and in 51 persons with essential hypertension. Calcitriol (p less than 0.008) and parathyroid hormone (p less than 0.01) levels were elevated in hypertensives with low renin activity, whereas calcitonin levels were higher in patients with high renin activity (p less than 0.008), compared with normotensive controls and other hypertensive patients. Continuous relationships were observed between calcitriol levels and plasma renin activity in all patients (r = -0.65, p less than 0.001) and between parathyroid hormone levels and urinary sodium excretion in hypertensive patients with low renin activity (r = -0.63, p less than 0.01). Together, these results support a linkage between calcium metabolism and renin-sodium factors in essential hypertension. Calcium-regulating hormones and the renin-aldosterone system may coordinately mediate the blood pressure effects of differing dietary calcium and sodium intakes at the cellular level by altering cellular handling of monovalent and divalent ions.

Calcitonin↗
PubMed1986

Atrial antipressor natriuretic peptide: release mechanisms and vascular action in man.

Atrial natriuretic peptide (ANP) release into the human circulation, responses to cardiopulmonary volume changes and natriuretic and vasorelaxant effects were studied in 45 normal subjects and in 12 patients during diagnostic cardiac catheterization. A new radioreceptor assay with a detection limit of 2 fmol/tube for alpha-human ANP (alpha-hANP) was used. In normal subjects plasma ANP was 27.2 +/- 4 pmol/l (n = 45, range 2-80). Right atrial plasma ANP correlated with right atrial pressure (r = 0.813, P less than 0.01), and in four of the patients increases in ANP paralleled the rise in atrial pressure during bicycle ergometry. Reducing venous return by bilateral thigh-cuff occlusion decreased atrial ANP from 66.8 +/- 17.9 to 19.6 +/- 8.0 pmol/l (n = 6, P less than 0.05). Increasing cardiopulmonary volume during 3-h head-out water immersion was associated with an increase in ANP from 16.0 +/- 5.6 to 92.6 +/- 21.5 pmol/l (n = 7, P less than 0.01) followed by transient urinary sodium excretion. The natriuretic threshold plasma ANP concentration during intravenous ANP infusion was 70-80 pmol/l. Atrial natriuretic peptide infused intra-arterially at a maximal forearm vasodilator dose (0.75 micrograms/min per 100 ml forearm tissue) increased forearm blood flow by 7.0 +/- 1.44 ml/min per 100 ml whereas the increase in sodium nitroprusside was 11.1 +/- 1.47 ml/min per 100 ml. Thus, ANP is rapidly released in response to atrial volume and pressure changes and represents a powerful vasodilating and, at high concentrations, natriuretic hormone in man.

Adolescent↗
PubMed1986

Angiotensin converting enzyme inhibition and calcium channel blockade as primary antihypertensive therapy.

Recent large-scale antihypertensive treatment trials primarily emphasize the quality of blood pressure control for reduction of cerebrovascular accidents as well as for myocardial infarction, practically irrespective of the type of drug used. Therefore, the best drug that normalizes blood pressure without adverse effects should be sought. On the basis of studies demonstrating cellular membrane and calcium homoeostatic derangements, and an age-dependent transition of overall cardiovascular regulation and peripheral vasoconstrictor forces during the course of essential hypertension, an alternative treatment concept is proposed: angiotensin converting enzyme inhibitors or beta-blockers can primarily be used in younger patients and those with a high renin, while calcium antagonists are used in place of diuretics in older, low-renin or black patients. Age-oriented two-way drug selection enables normalization of blood pressure without untoward effects in about 80% of patients with essential hypertension, and helps to optimize drug combinations in those patients who are difficult to treat.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1986

Altered platelet phosphatidylinositol metabolism in essential hypertension.

The metabolism of phosphoinositides was investigated in platelet membranes from nine patients with essential hypertension (EHT) and from 10 age/sex-matched normotensive subjects. 32P-labelling or phosphatidic acid (PA), phosphatidylinositol (PI), phosphatidylinositol-4-phosphate (PIP) and phosphatidylinositol-4,5-bisphosphate (PIP2) was measured in lipid extracts prepared from resting 32P-prelabelled platelets. There were no differences in 32P-PA between subject groups. In platelets of hypertensive patients, 32P-incorporation into both PIP and PIP2 was greater (P at least less than 0.01). This increase apparently occurred at the expense of lower 32P-incorporation into PI (P less than 0.001). An alteration in the interconversion equilibrium between phosphoinositides which is directed towards polyphosphoinositide formation may lead to altered membrane ionic fluxes.

Adult↗
PubMed1985

Age, race, blood pressure and renin: predictors for antihypertensive treatment with calcium antagonists.

Age, race, pretreatment blood pressure and plasma renin activity have been related to the antihypertensive response to calcium antagonists in studies that included 215 patients with mild to moderate essential hypertension. Adverse effects necessitated withdrawal from therapy in about 10% of the patients. All calcium antagonists lowered blood pressure significantly and comparably without weight gain or reflex tachycardia. In a multiple linear regression analysis of 138 white patients, age, pretreatment blood pressure and renin activity were of independent and significant predictive value for the antihypertensive response. Stratification of patients into 3 age groups disclosed a greater effect in patients older than 60 years compared with those between 40 and 60 years and those below 40 years, respectively (p less than 0.01). In 16 middle-aged black patients, antihypertensive therapy with a calcium antagonist proved highly efficacious. Monotherapy with a calcium antagonist may become a first-line treatment for essential hypertension, particularly in older patients who have low renin activity and possibly in black patients as well.

Adolescent↗
PubMed1985

Adrenoceptors, calcium, and vasoconstriction in normal and hypertensive humans.

The sympathetic nervous activity contributes to the pathophysiology of essential hypertension in an early phase and in younger patients mainly through increased beta-adrenoceptor-mediated functions and in a later phase and in older patients in whom beta-adrenoceptor-mediated functions are blunted, through increased alpha-adrenoceptor-mediated and calcium-influx-dependent vasoconstriction. Intracellular free calcium concentration is elevated in platelets of hypertensive patients and relates directly to the degree of their blood pressure, likely reflecting increased intracellular calcium concentration in vascular smooth muscle cells. A sympathetic factor is suggested further by the enhanced alpha 1-and alpha 2-adrenoceptor-mediated and calcium influx-dependent, vasoconstriction both of which are normalized by antihypertensive treatment in parallel with a normalization of intracellular free calcium and of the increased adrenaline sensitivity of platelets. The higher sensitivity to adrenaline for thrombin-induced calcium increases in platelets of hypertensive patients indicates potentiation of calcium influx (and mobilization from intracellular stores) by adrenaline, a mechanism that is mediated by alpha 2-adrenoceptors. As this effect is more pronounced in younger patients, increased adenylate cyclase sensitivity may prevail in the early and alterations in calcium influx-dependent mechanisms in the later phase of essential hypertension. The transition into a hypertensive state with reduced-reflex cardiovascular counterregulation codetermines the antihypertensive effectiveness of calcium antagonists in these patients.

Arm↗
PubMed1985

Position of calcium antagonists in antihypertensive therapy.

More than 20 years ago calcium antagonists were shown to lower elevated blood pressure. Today's worldwide recognition, at least in part, is due to rising research interest in cellular ion regulation abnormalities in essential hypertension. Using the human platelet as a model for the vascular smooth muscle cell, a direct relationship was observed between intracellular free calcium concentration and the height of blood pressure before as well as during different antihypertensive treatments. Calcium influx is an important determinant of vasoconstriction, and excess calcium influx-dependent vasoconstriction was shown with plethysmographical studies in patients with essential hypertension. Calcium antagonists acutely lower blood pressure by reducing intracellular calcium and peripheral vascular resistance. The degree of the attendant sympathetic nerve reflex activation and counterregulatory mechanisms codetermine the antihypertensive result of the individual. Chronic monotherapy with calcium antagonists results in an antihypertensive response that is related directly to the patient's age and pretreatment blood pressure and indirectly to renin. These studies led to a new treatment concept: calcium antagonists can be used as alternatives to diuretic drugs primarily in the older and low-renin patients and beta-blockers or converting enzyme inhibitors can be used in the younger or high-renin patients with greater efficacy. With the appropriate choice, calcium antagonists alone or combined with any other antihypertensive drug provide good blood pressure control with little subjective and objective adverse effects.

Adrenergic beta-Antagonists↗
PubMed1985

Exercise and resting blood pressure and heart rate changes 24 h after dosing in patients with essential hypertension receiving 16/260 oxprenolol Oros once daily.

Nineteen patients receiving oxprenolol slow-release (SR) 160 mg (three patients) or 320 mg (16 patients) once daily for mild to moderate hypertension were treated with oxprenolol Oros 16/260 once daily for 3 weeks following a 2 week placebo wash-out period. Repeated dosing with both Oros and SR oxprenolol preparations, in comparison with placebo, significantly reduced supine systolic and diastolic blood pressures, and pulse rate at 24 h after dosing. Single Oros doses also significantly reduced pulse rate and diastolic, but not systolic, blood pressure at 24 h. The reduction in supine systolic blood pressure was greater during repeated dosing with oxprenolol SR than after a single dose of the Oros preparation. Control of supine diastolic blood pressure (less than or equal to 90 mm Hg) at 24 h after dosing was achieved in 13 out of 18 patients with oxprenolol SR (two out of three patients given 160 mg, and 11 out of 15 given 320 mg). Similar control was achieved in 11 out of 18 patients after a single dose of oxprenolol Oros, and in 13 out of 17 patients treated for 3 weeks. The mean percentage reduction in exercise heart rate (EHR) compared to placebo, at 24 h after dosing, was 16% following Oros treatment for 3 weeks, and 12% following SR administration. After a single dose of oxprenolol Oros EHR, was reduced by 9% at 24 h compared to placebo. At 3 weeks the Oros formulation was significantly better than the SR tablet at reducing EHR. Oxprenolol Oros 16/260 was effective over 24 h and well tolerated.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Transient enhancement of sympathetic nervous system activity by long-term restriction of sodium intake.

To further investigate the relationship between salt intake and sympathetic nervous system activity, the short- and long-term effects of a low-salt diet (40 meq/day) were assessed in 10 normal subjects. Measurements of hemodynamic, hormonal, and other parameters were obtained on the day preceding institution of the low-salt diet (day 0) and on days 4, 7, 30, and 60 of the diet. Urinary sodium excretion was 178 +/- 10 meq/24 hr on day 0 and 31 +/- 4, 38 +/- 4, 45 +/- 6, and 47 +/- 7 meq/24 hr on days 4, 7, 30, and 60, respectively (all p less than .001 compared with day 0). Blood pressure, urinary potassium, serum electrolytes, and cardiac function (as assessed by echocardiography) were not modified by the 2 month low-salt diet. Plasma renin activity and plasma aldosterone were significantly elevated above control values throughout the entire period of the low-salt diet. In contrast, plasma norepinephrine concentration increased significantly only on days 4 and 7 (from 253 +/- 20 pg/ml on day 0 to 495 +/- 32 pg/ml, p less than .001, and 347 +/- 22 pg/ml, p less than .05, respectively), returning to baseline at days 30 (280 +/- 18 pg/ml) and 60 (262 +/- 18 pg/ml). Changes in plasma epinephrine paralleled those observed for norepinephrine. Similarly, resting heart rate and the blood pressure response to isometric exercise were significantly increased only on days 4 and 7 of the low-salt diet. These results suggest that sympathetic nervous system activity is enhanced only transiently during a sustained reduction in sodium intake.

Adult↗
PubMed1985

Antihypertensive therapy and myocardial infarction: focus on calcium antagonists.

Effective antihypertensive therapy has recently been shown to reduce not only the incidence of stroke, but also myocardial infarction irrespective of the drug(s) used. The well-documented preventive effect of beta-blockers in patients who suffered a myocardial infarction (secondary prevention) cannot be extended to patients with hypertension without overt coronary artery disease (primary prevention), except perhaps for non-smoking men. Despite strong experimental evidence, information on a possible secondary preventive effect of calcium antagonists in man is scant, and two double-blind placebo-controlled trials in secondary prevention with verapamil (320 mg) in a total of 1436 patients and nifedipine (30 mg) in 2279 patients did not reveal an overall treatment benefit. There are another six on-going trials. In the management of hypertension, large-scale trials may never help in selecting a particular drug for cardiac event reduction, and probably for many years the goals will be to normalize blood pressure with increased emphasis on the need to remedy other cardiovascular risk factors, in particular smoking.

Adrenergic beta-Antagonists↗
PubMed1984

[Aggression inhibition and increased sympathetic nervous reactivity in the development of essential hypertension].

Suppressed aggression and activity of the sympathetic nervous system were assessed in two risk groups for essential hypertension, viz. 24 borderline hypertensives (18 men, 6 women, age range 18-24, 18 with a family history of hypertension) and 24 normotensive offspring of hypertensive parents, and in a control group exactly matched for age, sex and socioeconomic status. In the Rosenzweig Picture-Frustration test, both potential hypertensive groups were significantly less aggressive compared with the controls, and additionally the borderline hypertensives internalized their aggression. Plasma noradrenaline concentrations, as a marker for sympathetic nervous system activity, increased significantly before and during mental stressors (Stroop colour-word conflict test, mental arithmetic) in both groups, whereas in normotensive controls no significant increase occurred. These findings point to a psychosomatic factor in the development of essential hypertension.

Adolescent↗
PubMed1984

Use of calcium antagonists as monotherapy in the management of hypertension.

A wide variety of drug treatments are available for the management of hypertension. Often, effective therapy is found only through a process of elimination. A more pathophysiologically oriented method of choosing therapy is based on classification of patients into those with low-, normal-, and high-renin hypertension. In the past, for example, diuretics were considered to be the most effective agents for the treatment of low-renin hypertension. Most cases of essential hypertension are characterized by increased vascular resistance. Calcium channel influx is a major determinant of the free intracellular calcium concentration that finally triggers the contractile process of the vascular smooth muscle cell and thereby determines arterial resistance. In man, free calcium concentration in platelets is closely related to the height of systolic and diastolic blood pressure. Vasodilatation produced by the intra-arterial infusion of a calcium channel blocker into the forearm circulation is significantly greater in hypertensive patients than in normotensive subjects, threefold that observed with sodium nitroprusside, and fourfold that found with prazosin. In hypertensive patients, these effects are correlated directly with plasma epinephrine--reflecting sympathoadrenal activity--and inversely with the activity and reactivity of the renin-angiotensin system. In several clinical studies, the decrease in blood pressure following the administration of calcium channel entry blockers was directly correlated to the patient's age and pretreatment blood pressure, and indirectly to the pretreatment plasma renin activity. The effects of these agents are apparently also comparable to the over-all responses achievable with beta blockers and diuretics. In the future, calcium entry blockers may replace diuretics as first-line therapy for older patients and those with low-renin hypertension.

Calcium↗
PubMed1984

Antihypertensive therapy with the long-acting calcium antagonist nitrendipine.

The antihypertensive efficacy of the calcium entry blocker nitrendipine administered as monotherapy (20-80 mg; mean, 36/day) on the average for 144 days to 46 patients with essential hypertension (WHO I and II) was investigated in relation to age, pretreatment blood pressure, and plasma renin activity. In addition, we compared the blood pressure responses to verapamil (n = 11) and nifedipine (n = 15) with those to nitrendipine. Nitrendipine monotherapy reduced blood pressure from 168 +/- 16/107 +/- 7 mm Hg to 145 +/- 13/91 +/- 6 (both p less than 0.001); in 33 of 46 patients a diastolic pressure less than or equal to 95 mm Hg was achieved. During long-term treatment, heart rate and body weight remained unchanged. Thirteen of 16 patients in whom blood pressure was measured 24 h after a single oral dose (20 to 40 mg) reached a diastolic pressure less than or equal to 95 mm Hg. Treatment with nitrendipine had to be discontinued because of severe headache in two and ankle oedema in one patient. The fall in mean blood pressure after nitrendipine was directly related to age (r = 0.553; p less than 0.001) and pretreatment mean blood pressure (r = 0.470; p less than 0.01) and inversely related to plasma renin activity (r = 0.558; p less than 0.001). These correlations were also significant for systolic and diastolic blood pressure. There was comparable antihypertensive efficacy, as expressed by changes in mean blood pressure, between nitrendipine and verapamil (r = 0.869; p less than 0.01), and nitrendipine and nifedipine (r = 0.953; p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗