PubMed Health⌕ Search

Biomedical subjects

A B Weder

Publications and source records attributed to A B Weder.

At least 55 records · Page 3Linked to original sources
PubMed1990

On the asymmetry of biological frequency distributions.

The long-standing problem of determining whether the skewness in a sample frequency distribution is the manifestation of the intermixing of disparate groups characterizable by a normal mixture distribution or the manifestation of non-mixture, skew-producing determinants is discussed. Biometrical tools for modeling and quantifying the significance of the skewness in a trait of interest that invite interpretations other than those formed in mixtures or "subgroups" are elaborated. Statistical methods for testing whether a normal mixture distribution better characterizes a set of data than the proposed (or any other) skewed, single-population-oriented models are offered. The power of these tests is examined through Monte Carlo experimentation. A brief application in hypertension research demonstrates some of the problems and methods discussed in the paper.

Blood Pressure↗
PubMed1990

Disease entities, mixed multi-normal distributions, and the role of the hyperkinetic state in the pathogenesis of hypertension.

This paper concerns the theory and relevance of finite mixtures of univariate and multivariate normal distributions in medical research and suggests that multivariate normal mixture analysis, hitherto not extensively explored, is an appealing approach to the investigation of etiologically obscure, multifactorial diseases such as hypertension. We elaborate a statistical strategy to resolve and test for a normal mixture distribution in a seemingly heterogenous population actually comprising homogenous subpopulations. We use this strategy to validate the hypothesis that in the population at large there is a subgroup of individuals with the characteristic of a hyperkinetic circulatory state, defined as the association of an elevated cardiac index or heart rate with high blood pressure. This subgroup may have implications for the pathogenesis of hypertension. We discuss directions and implications for future research into the pathogenesis of hypertension.

Cluster Analysis↗
PubMed1990

Hemodynamic effects of quinapril, a novel angiotensin-converting enzyme inhibitor.

The hemodynamic effects of quinapril, a novel nonsulfhydryl-containing angiotensin-converting enzyme (ACE) inhibitor, were assessed in 10 patients with mild-to-moderate essential hypertension. Compared with placebo, quinapril (20 mg) administered twice daily for 4 weeks significantly lowered blood pressure by decreasing total peripheral resistance without producing tachycardia, an increase in cardiac output, or a rise in plasma catecholamines. Quinapril significantly reduced renal, but not forearm, vascular resistance. Renal blood flow, glomerular filtration rate, and filtration fraction remained unchanged. Left ventricular wall stress was markedly reduced by quinapril, but during the relatively short treatment period, only a nonsignificant trend toward reduction in left ventricular mass was observed. These findings suggest that quinapril is an effective antihypertensive agent that lowers peripheral resistance without increasing cardiac output or disturbing autoregulation of renal hemodynamics.

Adult↗
PubMed1990

Aerobic physical training and alterations in pressor response during norepinephrine infusion: a controlled single-subject experiment.

To test the influence of aerobic physical training on pressor response to infused norepinephrine, the present study utilized a single subject A-B-A-B withdrawal design consisting of 9-week alternating sedentary and aerobic phases (S1, A1, S2, A2). During each 9-week phase the subject underwent infusions every 3 weeks, consisting of saline, low-dose and high-dose norepinephrine (Low-NE, High-NE). Heart rate and mean arterial blood pressure were monitored continuously; resting platelet and plasma catecholamines were also measured. Infusions were conducted 48 h from the most recent exercise bout to minimize residual effects of acute exercise. Fitness level was confirmed by VO2max during graded exercise testing at the conclusion of each 9-week phase. Blood pressure during saline did not differ between aerobic and sedentary phases. However, in all but one comparison, aerobic fitness was associated with a highly significant reduction in pressor response during Low-NE as well as High-NE. Plasma norepinephrine was higher during the two aerobic phases; platelet catecholamines and plasma epinephrine showed no reliable association with fitness. Results for this subject support an attenuation of pressor response associated with aerobic conditioning.

Adult↗
PubMed1990

Renal protective effects of angiotensin converting enzyme inhibitors.

Renal dysfunction and hypertension are closely associated. Hypertension causes approximately 25% of end-stage renal disease (ESRD) and develops in virtually every patient with advanced renal insufficiency from any cause. Although normalization of blood pressure can reduce mortality from uremia and ameliorate the progression of renal impairment in patients with established renal insufficiency from hypertension and diabetes, antihypertensive therapy alone is not totally effective in preventing progressive compromise of renal function--especially in blacks and diabetics, who are at high risk for developing ESRD. Of particular promise is the rapidly increasing understanding of the intrarenal autocrine and paracrine functions of angiotensin II produced locally by a tissue renin-angiotensin system. Consistent and convincing experimental data have demonstrated that angiotensin II plays many roles in the control of renal function and the kidney's response to injury. The intrarenal effects of angiotensin II include: 1) increase in the efferent arteriolar tone, resulting in increased glomerular capillary pressure, 2) promotion of mesangial cell contraction, 3) stimulation of proximal tubular Na+ reabsorption, and 4) possible growth hormone effects leading to hypertrophy or hyperplasia of vascular smooth muscle. Because of their favorable intrarenal hemodynamic effects (particularly reduction of glomerular capillary pressure), ACE inhibitors may provide a renal protective effect in addition to their systemic antihypertensive effects. Clinical trials evaluating the effect of ACE inhibition on the progression of renal insufficiency in hypertensives and diabetics are currently under way. Favorable results could lead to a significant decrease in the morbidity and mortality associated with hypertension.

Angiotensin II↗
PubMed1990

Platelet volume responses to cytoplasmic acidification in essential hypertension.

Using a Coulter-based cell sizing method, we have previously demonstrated that, in response to cytoplasmic acidification by 140 mmol/l sodium propionate, both the mean initial rate of amiloride-sensitive platelet volume swelling and the net volume change achieved at steady-state are greater in essential hypertensives than in normotensives. In the present study, we extend this observation by showing that, in response to graded propionate exposure (56-140 mmol/l), steady-state amiloride-sensitive volume responsiveness (as percentage increase over baseline) increases linearly, and the mean slope of the line relating amiloride-sensitive volume change and propionate concentration is increased in hypertensives (0.40 +/- 0.02 versus 0.32 +/- 0.02% per mmol/l propionate, P less than 0.003). In 56 mmol/l propionate, average amiloride-sensitive platelet swelling is significantly less in hypertensives than in normotensives (7.6 +/- 0.8 versus 11.1 +/- 0.9%, P less than 0.05), but in 140 mmol/l propionate, swelling is significantly increased in hypertensives (40.8 +/- 1.7 versus 36.2 +/- 1.5%, P less than 0.05). Since platelet intracellular calcium concentration is elevated in some hypertensives and Ca2+ is known to stimulate Na(+)-H+ antiport, the transport system that is the primary determinant of amiloride-sensitive cell swelling during propionate incubation, we studied the effects of the Ca2+ ionophore, ionomycin, on volume regulation. In both normotensives and hypertensives, ionomycin (2 x 10(-10 to 2 x 10(-7) mol/l) causes dose-related increases in amiloride-sensitive platelet swelling during graded propionate exposure.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Regional hemodynamic abnormalities in overweight men. Focus on alpha-adrenergic vascular responses.

Blood pressure, forearm hemodynamic data, and red blood cell (RBC) cation transport measurements were obtained in 27 men with body mass indexes (BMI) greater than 26.6 kg/m2 and 21 men with BMI less than 26.6 kg/m2. Subjects with higher BMI had significantly higher systolic and diastolic pressure measured both noninvasively and invasively, P less than .02-.001. Baseline forearm blood flow (FABF) was substantially higher in the heavier subjects, P less than .02, whereas forearm vascular resistance (FAVR) levels were not different, P greater than .10. Despite the higher baseline forearm blood flow, the high BMI group displayed a greater rise in flow, P less than .01, in response to a regional phentolamine infusion, an index of vascular alpha-tone. Results of multiple regression analysis suggested that overweight was indirectly correlated with vascular alpha-tone via a relationship with arterial plasma norepinephrine concentration, a marker of sympathetic drive, and bumetanide-sensitive RBC Na+-K+ cotransport activity. These data indicate that in overweight men (1) higher FABF is not fully counter-balanced by lower FAVR; (2) increased vascular alpha-tone contributes to the altered flow-resistance relationship and thereby to the elevated blood pressure; and (3) greater sympathetic drive and Na+-K+ cotransport activity may explain the elevated vascular alpha-tone.

Blood Vessels↗
PubMed1989

Platelet intracellular pH in essential hypertensives and normotensives.

Using the intracellularly trapped pH-sensitive fluorescent dye, BCECF, basal intracellular pH was measured in 18 essential hypertensives and 23 normotensives. The average intracellular pH was slightly, but not significantly, lower in the hypertensives (7.173 +/- 0.017 versus 7.211 +/- 0.014, P = 0.09). Although basal intracellular pH is not significantly altered in hypertension, abnormal regulation of intracellular pH during growth factor or agonist stimulation may play a role in the development or maintenance of hypertension.

Adult↗
PubMed1989

Behaviour and hypertension: a pathophysiological puzzle.

Patients with borderline hypertension typically show enhanced sympathetic and decreased parasympathetic tone, characteristic personality traits (submissiveness, hostility) and hyperreactivity to mental stress. It has been proposed that the hypertensive personality results in a persistent 'defence reaction', enhancing sympathetic outflow from the central nervous system and reactivity to stress. But evidence from pharmacological intervention trials suggests that blood pressure reactivity is controlled independently of average baseline blood pressure. A study comparing the effects of the centrally-acting alpha 2-agonist, clonidine, and the selective beta 1-blocker, atenolol, demonstrated that both drugs had a comparable antihypertensive action on baseline blood pressure. However, neither agent affected stress responses to mental arithmetic, submaximal isometric handgrip exercise or cold pressor testing. We conclude that studies of stress reactivity, while of interest to students of circulatory control, are unlikely to yield insights into the causes of human hypertension.

Arousal↗
PubMed1989

Mixture analysis of erythrocyte lithium-sodium countertransport and blood pressure.

This study employs multivariate normal mixture analysis, a technique for identifying discrete subgroups within populations, to examine the relation of erythrocyte lithium-sodium (RBC Li+-Na+) countertransport and blood pressure in a group of 474 healthy adults. After adjusting for effects of age, gender, race, height, and weight, univariate mixture analysis of the distribution of mean arterial blood pressure (MAP) revealed the presence of only one group, whereas the distribution of RBC Li+-Na+ countertransport values was composed of a mixture of two groups (p less than 0.00005). When bivariate mixture analysis was applied to the combined distribution of MAP and RBC Li+-Na+ countertransport, two commingled subgroups were identified (p less than 0.00005). The smaller group (19%) had significantly higher values for both MAP (108.7 +/- 16.7 mm Hg, mean +/- SD) and RBC Li+-Na+ countertransport (0.455 +/- 0.147 mmol Li+/l cells.hr) than the larger (81%) group (MAP 93.3 +/- 12.2 mm Hg, RBC Li+-Na+ countertransport 0.247 +/- 0.080 mmol Li+/l cells.hr, p less than 0.0001 for both differences). The relation of MAP to RBC Li+-Na+ countertransport was distinctly different in these two subgroups. In the larger group, we found a weak positive (r = 0.21, p less than 0.0001) correlation for unadjusted values, which was not significant after adjustment. The smaller group, with higher levels of MAP and RBC Li+-Na+ countertransport, showed significant negative correlations for both unadjusted (r = -0.28, p less than 0.008) and adjusted (r = -0.41, p less than 0.0001) values.

Adult↗
PubMed1989

Brain and the regulation of blood pressure: a hemodynamic perspective.

The central nervous system subserves the homeostasis of the circulation and is organized as a negative feedback system. The following properties of such a feedback system are of interest: a) the setting; b) the range of the regulation; and c) the nature of the feedback (regulated) variable. In this review we show that in hypertension blood pressure is set at a higher level, but regulation of blood pressure in hypertension is normal. The central nervous system is involved in maintaining a higher set point in early human hypertension as well as in many forms of experimental hypertension. Results from trials of antihypertensive drugs suggest that setting of the baseline level of blood pressure and regulation of blood pressure variability are independent properties and are probably regulated by different areas of the central nervous system. It is, therefore, unlikely that research on blood pressure "reactivity" will elucidate the pathophysiology of the central resetting of baseline blood pressure level in hypertension. We present evidence that in subserving the circulation, the central nervous system regulates and senses blood pressure and not flow. Pathophysiologic implications of this concept are discussed particularly in regards to the apparent decrease of sympathetic tone during the evolution of hypertension.

Animals↗
PubMed1989

Platelet sodium-proton exchange is increased in essential hypertension.

Transmembrane sodium-hydrogen (Na+-H+) exchange was measured indirectly in human platelets as the amiloride-sensitive change in volume during incubation in isosmotic sodium propionate. After first establishing the reproducibility of the assay, we measured propionate-activated volume increases in platelets from 24 male essential hypertensive patients and 20 male normotensives. For the entire group, platelet Na+-H+ exchange was significantly (P less than 0.006) higher in hypertensives compared with normotensives. Unlike red blood cell (RDC) cation transport markers of hypertension, platelet Na+-H+ exchange was elevated in both black and white hypertensives. Na+-H+ exchange was significantly positively correlated with diastolic blood pressure and did not correlate significantly with age, body weight or body mass index. In addition, platelet Na+-H+ exchange did not correlate significantly with red blood cell lithium-sodium countertransport activity. Platelet Na+-H+ exchange deserves further study as a marker for pathophysiological abnormalities in human hypertension.

Blood Platelets↗
PubMed1989

Captopril inhibits ouabain-sensitive Na+/K+-ATPase.

Captopril has been reported to inhibit ouabain-sensitive Na+/K+-ATPase activity in erythrocyte membrane fragments. We investigated the effect of captopril on two physiological measures of Na+/K+ pump activity: 22Na+ efflux from human erythrocytes and K+-induced relaxation of rat tail artery segments. Captopril inhibited 22Na+ efflux from erythrocytes in a concentration-dependent fashion, with 50% inhibition of total 22Na+ efflux at a concentration of 4.8 X 10(-3) M. The inhibition produced by captopril (5 X 10(-3) M) and ouabain (10(-4) M) was not greater than that produced by ouabain alone (65.3 vs. 66.9%, respectively), and captopril inhibited 50% of ouabain-sensitive 22Na+ efflux at a concentration of 2.0 X 10(-3) M. Inhibition by captopril of ouabain-sensitive 22Na efflux was not explained by changes in intracellular sodium concentration, inhibition of angiotensin-converting enzyme or a sulfhydryl effect. Utilizing rat tail arteries pre-contracted with norepinephrine (NE) or serotonin (5HT) in K+-free solutions, we demonstrated dose-related inhibition of K+-induced relaxation by captopril (10(-6) to 10(-4) M). Concentrations above 10(-4) M did not significantly inhibit K+-induced relaxation but did decrease contractile responses to NE, although not to 5HT. Inhibition of K+-induced relaxation by captopril was not affected by saralasin, teprotide or indomethacin. We conclude that captopril can inhibit membrane Na+/K+-ATPase in intact red blood cells and vascular smooth muscle cells. The mechanism of pump suppression is uncertain, but inhibition of ATPase should be considered when high concentrations of captopril are employed in physiological studies.

Animals↗
PubMed1988

Erythrocyte water, Na+-K+ cotransport, and forearm vascular function in humans.

We examined the relationships between erythrocyte (RBC) composition (Na+, K+, and water content) and ouabain-insensitive transports (Na+-K+ cotransport, Li+-Na+ countertransport) and forearm vascular hemodynamics under standardized basal conditions and during vasoconstriction (intra-arterial infusion of graded doses of norepinephrine and angiotensin II) and vasodilation (intra-arterial phentolamine and postischemic exercise). RBC water content correlated positively and significantly (r = 0.53, p = 0.001) with minimum forearm vascular resistance, a measure of vascular structural change, and negatively with maximal forearm blood flow (r = -0.55, p less than 0.001). Similar correlations with forearm vascular resistance and blood flow were observed under all experimental conditions. RBC Na+-K+ cotransport correlated positively and significantly (r = 0.43, p = 0.01) with the change in forearm blood flow produced by phentolamine, a functional measure of alpha-adrenergic tone, and was as strong an independent predictor of phentolamine-induced blood flow change as was arterial norepinephrine concentration. RBC Na+-K+ cotransport was also significantly positively correlated with residual forearm blood flow and resistance after phentolamine administration, where nonadrenergic influences predominate. RBC water correlated negatively with Li+-Na+ countertransport (r = -0.33, p less than 0.05) and Na+-K+ cotransport (r = -0.44, p less than 0.01). We propose that RBC water is a marker for a vascular structural property that contributes to vascular reactivity. RBC Na+-K+ cotransport seems to relate most strongly to the sympathetically mediated control of forearm blood flow and may also be linked to the intrinsic myogenic tone of the forearm vasculature.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Atrial natriuretic hormone is not elevated during dopamine induced natriuresis.

To evaluate the possibility that atrial natriuretic hormone (ANH) is involved in dopamine induced natriuresis and diuresis, we studied five normal male volunteers. Each was studied on two occasions. During the first two hours of each study, normal saline, 25 ml/hr, was infused. During the second two hours either normal saline, 25 ml/hr, or dopamine, 4 micrograms/kg/min, in normal saline, was infused. Dopamine infusion caused prominent and significant natriuresis and diuresis but plasma levels of immunoreactive ANH levels did not change. We conclude that the ANH is not involved in dopamine induced natriuresis and that dopaminergic stimulation is not responsible for ANH secretion.

Adult↗
PubMed1987

Hormonal responses to cardiac tamponade: inhibition of release of atrial natriuretic factor despite elevation of atrial pressures.

Atrial distension, rather than change in intra-atrial pressure, has been suggested as a principal mediator of release of atrial natriuretic factor (ANF). During cardiac tamponade, atrial pressures rise whereas transmural pressures and atrial stretch may not be affected. The roles of atrial pressure and atrial distension were investigated in six open-chest dogs subjected to cardiac tamponade and rapid volume expansion as disparate means of affecting intra-atrial pressures and atrial stretch. Hemodynamic measurements, immunoreactive ANF (ir-ANF), plasma renin activity, antidiuretic hormone, epinephrine, and norepinephrine were monitored before, during, and after three interventions: (1) tamponade, (2) rapid volume loading followed by tamponade, and (3) volume loading during tamponade. Volume expansion increased right atrial pressure and caused a significant rise in ir-ANF. Elevations of right atrial pressure caused by tamponade were comparable to those induced by volume infusion, but an increase in ir-ANF was not elicited during tamponade, and the ir-ANF response to volume loading was abolished when performed during tamponade. The relation between the change in ANF concentration and change in right atrial pressure were highly significant in the absence of tamponade, when atrial stretch was freely responsive to volume expansion (r = .73, p less than .0001), but not when stretch was inhibited (r = -.16, p = NS). These observations underscore the importance of considering the modulating effects of atrial compliance, transmural pressure, and atrial stretch on the relation between atrial pressures and ANF release.

Animals↗