PubMed Health⌕ Search

Biomedical subjects

M H Weinberger

Publications and source records attributed to M H Weinberger.

At least 19 recordsLinked to original sources
PubMed1998

Influence of race and dietary salt on the antihypertensive efficacy of an angiotensin-converting enzyme inhibitor or a calcium channel antagonist in salt-sensitive hypertensives.

Dietary salt restriction is a recommended adjunct with antihypertensive therapy. There may be racial differences in blood pressure response to salt restriction while on antihypertensive therapy. We performed a multicenter, randomized, double-blind, placebo-controlled, parallel-group clinical trial (black, n=96; Hispanic, n=63; white, n=232). Participants were initially preselected for stage I to III hypertension and then further selected for salt sensitivity (> or = 5 mm Hg increase in diastolic blood pressure after 3 weeks of low salt [< or = 88 mmol/d Na+] and high salt [>190 mmol/d Na+] diet). We compared the antihypertensive effect of an angiotensin-converting enzyme inhibitor (enalapril 5 or 20 mg BID) or a calcium channel antagonist (isradipine 5 or 10 mg BID) during alternating periods of high and low salt intake. The main outcome measure was blood pressure change and absolute blood pressure level achieved with therapy. During the high salt diet (314.7+/-107.5 mmol/d urinary Na+) there was greater downward change in blood pressure with both enalapril and isradipine compared with the low salt diet (90.1+/-50.8 mmol/d Na+); however, the absolute blood pressure achieved in all races was consistently lower on a low salt diet for both agents. Black, white, and Hispanic isradipine-treated salt-sensitive hypertensives demonstrated a smaller difference between high and low salt diets (black, -3.6/-1.6 mmHg; white, -6.2/-3.9 mmHg; Hispanic, -8.1/-5.3 mm Hg) than did enalapril-treated patients (black, -9.0/-5.3 mm Hg; white, -11.8/-7.0 mm Hg; Hispanic, -11.1/-5.6 mm Hg). On the low salt diet, blacks, whites, and Hispanics had similar blood pressure control with enalapril and isradipine. On the high salt diet, blacks had better blood pressure control with isradipine than with enalapril, whereas there was no difference in the blood pressure control in whites and Hispanics treated with either drug. Dietary salt reduction helps reduce blood pressure in salt-sensitive hypertensive blacks, whites, and Hispanics treated with enalapril or isradipine. These data demonstrate that controlling for salt sensitivity diminishes race-related differences in antihypertensive activity.

Adult↗
PubMed1997

There are no racial, age, sex, or weight differences in the effect of salt on blood pressure in salt-sensitive hypertensive patients.

BACKGROUND: This report is part of a larger, multicenter, placebo-controlled study designed to test the effects of low and high salt intake on the antihypertensive action of enalapril maleate or isradipine in salt-sensitive, hypertensive patients. OBJECTIVE: To present our findings with respect to the effects of race, age, sex, and weight on the blood pressure response to low and high salt intake in salt-sensitive hypertensive patients before randomization into the larger study. PATIENTS AND METHODS: After 3 week (weeks -9 to -6) of ad lib salt intake (100-200 mmol/d of sodium), 1916 patients whose sitting diastolic blood pressure was between 95 and 115 mm Hg entered a 3-week period (week -6 to -3) of low salt intake (50-80 mmol/d of sodium) and then a 3-week period (week -3 to 0) of high salt intake (200-250 mmol/d of sodium). Of the 1916 patients, 624 were identified as being sensitive to salt by demonstrating an increase in sitting diastolic blood pressure of equal to or more than 5 mm Hg from the low to high salt intake. Of these patients, 367 were white, 156 were black, 92 were Hispanic, 8 were Asian, and 1 was American Indian. Also, 315 were men and 309, women; 351 were 55 years or younger and 273 were older than 55 years; and 195 had a body mass index of 27 or less and 429 had a body mass index higher than 27. RESULTS: The sitting blood pressure decreased with salt restriction and increased with salt load in all groups of patients (P < .001). There were no statistically significant differences in the blood pressure changes to salt changes by race, age, sex, and weight. CONCLUSIONS: This large, multicenter study did not demonstrate any statistically significant effect of race, age, sex, and weight on blood pressure response to salt changes in salt-sensitive hypertensive patients.

Aging↗
PubMed1997

Heterogeneous responses to changes in dietary salt intake: the salt-sensitivity paradigm.

Blood pressure responses to increases and decreases in dietary salt intake are heterogeneous. In some hypertensive individuals, decreases in blood pressure with salt restriction are clinically significant and approach that achieved with medication. In others, little or no change in blood pressure occurs, whereas in still others, blood pressure may actually increase with salt restriction. The heterogeneous responses are partly acquired and involve the influences of age, the intake of other electrolytes, and the influence of certain medications. Genetic predisposition may also play a substantial role because salt sensitivity is increased in black individuals and in persons with non-insulin-dependent diabetes mellitus. Some uncommon but readily diagnosed salt-sensitive genetic syndromes, such as glucocorticoid-remediable aldosteronism and Liddle syndrome, have been identified. Short-term volume expansion and contraction and longer-term dietary interventions appear to be reproducible and may be used to identify salt-sensitive and salt-resistant individuals; however, these maneuvers are cumbersome and cannot be used on a large scale. Molecular genetic techniques for identifying individuals with salt-sensitive and salt-resistant essential hypertension are not yet available, but if the putative gene polymorphisms are identified, such techniques may replace the current trial-and-error methods.

Aging↗
PubMed1997

Compliance to a low-salt diet.

Community intervention projects, efforts at single centers, and multicenter, prospective, dietary salt-restriction trials suggest that such an intervention is neither easy to achieve nor simple to maintain. Community-wide interventions based on advertisements, pamphlets, posters, radio messages, instructions in schools or other institutions, and cooperation from food suppliers such as butchers and bakers resulted in a slight decrease in salt consumption, mostly in normotensive women. A demonstration project at a single center showed that lowering salt intake long-term by 50% in hypertensive patients was feasible. That study included self-administered, positive-feedback devices to indicate adherence and a role for a household partner in achieving compliance. Multicenter intervention trials also indicate that reducing salt intake in the long term is feasible. However, in all intervention trials the subjects were highly selected, stable, generally married male volunteers. An elaborate training program involving many health care professionals was necessary and recidivism was common. Successful intervention requires specific goals and delegated responsibilities on the part of the health care team, careful assessment of the patient and the risk factors, as well as motivation for behavioral change, a specific plan for implementation, repetitive educational efforts, and a built-in monitoring mechanism.

Cross-Over Studies↗
PubMed1996

Hemodynamic, renal, and hormonal responses to lower body positive pressure in human subjects.

Studies in healthy human subjects subjected to lower body positive pressure (LBPP) have failed to elucidate many of the physiologic effects of this maneuver. In 7 healthy, well-hydrated men we studied the following responses to LBPP (35 mm Hg, 1 hour, supine position): systemic and renal hemodynamics; urine volume (UV), urine osmolality (Uosm), and urine sodium level (UNaV); free water (CH20) and osmolar (Cosm) clearances; plasma renin activity (PRA); levels of aldosterone (PA), cortisol (CORT), norepinephrine (NE), atrial natriuretic peptide (ANP), and vasopressin (AVP); osmolality (Posm); and serum sodium level. Subjects were restudied on a control day with zero trouser pressure. The recorded changes (p < 0.05) when comparing the LBPP day with the control day were as follows: fractional Na+ reabsorption increased (98.7% +/- 0.2% to 99.3% +/- 0.1%) and UNaV decreased (0.19 +/- 0.03 mEq/min to 0.10 +/- 0.01 mEq/min), with concomitant increases in PRA (1.7 +/- 0.2 ng/ml/90 min to 4.5 +/- 1.8 ng/ml/90 min), PA (7.7 +/- 0.7 ng/dl to 9.3 +/- 1.5 ng/dl), and CORT (13.0 +/- 2.6 mg/dl to 19.2 +/- 3 mg/dl); the increase in blood pressure with LBPP (96 +/- 3 mm Hg to 112 +/- 4 mm Hg) was greater than that during control conditions. Renal plasma flow tended to display an interactive pattern across days, with a slight decline during LBPP (5%) and a slight elevation under control conditions (9%). On the LBPP day only, filtered Na+ declined (15 +/- I mEq/min to 12 +/- 1 mEq/min) as a function of reduced glomerular filtration rate (112 +/- 5 ml/min to 91 +/- 7 ml/min), blood volume decreased (by 2.7% +/- 0.7%), CO decreased (5.5 +/- 0.3 L/min to 4.7 +/- 0.3 L/min), and stroke volume declined (101 +/- 6 ml to 84 +/- 3 ml). On both days, NE increased (control, 221 +/- 23 pg/ml to 340 +/- 33 pg/ml; LBPP, 236 +/- 17 pg/ml to 369 +/- 31 pg/ml) and ANP increased (control, 47 +/- 7 pg/ml to 97 +/- 21 pg/ml; LBPP, 49 +/- 10 pg/ml to 104 +/- 30 pg/ml). We concluded that LBPP reduces renal sodium excretion. The mechanism for this reduction is not known, although it did occur in association with an increase in plasma renin activity, which in turn results from mechanical reduction of renal perfusion, stress-related CORT stimulation, a reflex-based elevation in peripheral vascular resistance leading to a reflex increase in plasma renin activity, or a combination of these.

Adult↗
PubMed1996

Salt sensitivity of blood pressure in humans.

A variety of different techniques have been used for the assessment of the blood pressure response to changes in salt and water balance in humans. These have generally been found to be reproducible and to yield congruent results. This review surveys the characteristics of subjects identified as salt sensitive and salt resistant by different investigators from demographic and physiological perspectives.

Blood Pressure↗
PubMed1996

Hypertension in African Americans: the role of sodium chloride and extracellular fluid volume.

African Americans show higher blood pressure earlier in life, and have a greater incidence of hypertension that is manifest earlier, is more severe and is associated with a greater risk of cardiovascular complications as compared with their white colleagues. Although a variety of mechanisms have been implicated in this phenomenon, a single abnormal factor is unlikely. The role of sodium (salt) sensitivity of blood pressure, renal function, related vasoactive factors, and intracellular ion transport systems will be briefly reviewed for their potential involvement. Speculative hypotheses concerning potential causes of the enhanced salt-sensitivity observed in African Americans will be offered. The implications of these findings for the treatment of hypertension in African Americans will also be briefly discussed.

Antihypertensive Agents↗
PubMed1995

Doxazosin lowers blood pressure and improves insulin responses to a glucose load with no changes in tyrosine kinase activity or insulin binding.

alpha-Adrenergic blockers have shown favorable metabolic effects. We evaluated the glucose and insulin responses to a glucose load and lipid profiles in 36 diabetic hypertensive patients before and after 8 weeks of doxazosin administration. To evaluate insulin action at the cellular level, erythrocyte insulin binding and tyrosine kinase (TK) activity were measured in 12 of these patients. Systolic and diastolic blood pressures decreased significantly (P < .0001) after 8 weeks of doxazosin therapy. Doxazosin administration significantly reduced the integrated insulin response (area under the curve [AUC]-insulin: 6093 +/- 894 to 5260 +/- 807; P = .04) and the insulin/glucose index (I/G) at 90 and 120 min after a glucose load (at 90 min, 0.230 +/- 0.055 v 0.180 +/- 0.04, P < .05; at 120 min, 0.275 +/- 0.071 v 0.173 +/- 0.036, P < .05). HDL3 level increased from 31.1 +/- 1.5 mg% to 34 +/- 1.6 mg% (P < .05) after doxazosin. Erythrocyte insulin binding and tyrosine kinase activity were not significantly altered after doxazosin. No significant correlation was found between the insulin or glucose responses and the insulin receptor binding or tyrosine kinase activity before and after treatment.

Blood Glucose↗
PubMed1995

Sodium homeostasis in primary and secondary forms of hypertension.

The role of extracellular fluid status and sodium balance in various forms of hypertension often has been difficult to define precisely because of the limitations of direct measurements of these factors. Isotopic measurements of various fluid volume compartments in the body have suffered from being insensitive and imprecise. Estimates of sodium content have also been difficult because of the ready diffusion of this ion among many body compartments. Studies of sodium balance utilizing metabolic ward techniques have been too time-consuming and arduous for large-scale investigations. Thus, inferences on the role of sodium and volume in blood pressure have been derived largely from indirect observations based on the response of blood pressure to manipulation of sodium or volume status, or both, and by changes in dietary sodium, or administration of intravenous sodium loads or diuretics. Such studies, while indirect and often crude in precision, have yielded important new insights into the etiology and pathogenesis of hypertension. The roles of agents that influence renal handling of sodium and water, and vascular biology are also being investigated for their influence on sodium homeostasis.

Animals↗
PubMed1994

Salt sensitivity and the blood pressure response to verapamil.

To evaluate the effect of salt responsiveness of blood pressure to the antihypertensive effect of calcium channel blockade, we studied 15 essential hypertensive patients who had previously been characterized with respect to salt sensitivity or resistance of blood pressure. After a placebo period, titration with verapamil in doses of 180 to 480 mg/day was begun until goal blood pressure responses were reached. The study population exhibited a significant (P < or = .007) reduction in systolic and diastolic blood pressure with treatment. There were no significant differences in the response to calcium channel blockade when the subjects were separated into salt-sensitive (n = 8) and salt-resistant (n = 7) subgroups. A significant (P < or = .05) correlation was observed between the age of the subjects and the blood pressure response. In this study verapamil lowered blood pressure in all subjects. We conclude that calcium channel blockade reduces blood pressure in essential hypertensive subjects during a normal sodium intake, independent of salt-sensitivity status.

Adult↗
PubMed1994

Mineralocorticoids and blood pressure.

Recent observations suggest that the syndrome of mineralocorticoid excess, primary aldosteronism, may be more common than has been previously believed. Enhanced detection of this syndrome has been simplified by the development of sensitive screening techniques. The diagnosis and differentiation of several different forms of primary aldosteronism have also been improved by new insights into the pathophysiology of these disorders and the application of several new techniques to distinguish them. The discovery of variable activity of several steroids on the mineralocorticoid receptor has provided additional understanding of the finding of the manifestations of hyperaldosteronism in the presence of normal aldosterone production. Finally, new approaches to the treatment of primary aldosteronism have also been developed.

Blood Pressure↗
PubMed1993

The diagnosis of primary aldosteronism and separation of two major subtypes.

BACKGROUND: To develop a simple screening and diagnostic test for primary aldosteronism and to compare it with established techniques. DESIGN: Comparison of several techniques for screening, diagnosis, and differentiation of primary aldosteronism using normotensive and hypertensive subjects. METHODS: Four hundred thirty-four normotensive subjects, 263 essential hypertensive subjects, 48 subjects with primary aldosteronism due to a unilateral adrenal adenoma, and 14 in whom primary aldosteronism was associated with findings of bilateral hyperaldosteronism were studied. Plasma renin activity and plasma aldosterone were measured in venous blood obtained at 8 AM after 2 hours of ambulation and compared with established suppressive (plasma aldosterone) and stimulatory (plasma renin activity) maneuvers used for the diagnosis of primary aldosteronism. RESULTS: The ratio of plasma aldosterone to plasma renin activity provided complete separation of patients with primary aldosteronism from the normal and essential hypertensive groups. Moreover, based on the use of traditional localizing procedures separating unilateral hyperaldosteronism due to a solitary adenoma from bilateral hyperaldosteronism, confirmed by surgical intervention in the former subgroup, the ratio provided differentiation of these two forms of primary aldosteronism. CONCLUSIONS: The use of the plasma aldosterone to plasma renin activity ratio appears to be useful in the screening, diagnosis, and differentiation of unilateral and bilateral forms of primary aldosteronism. These observations may also be applicable to patients receiving some antihypertensive medications.

Adult↗
PubMed1993

Racial differences in renal sodium excretion: relationship to hypertension.

Black Americans are more susceptible to hypertension and to renal disease than white Americans. Both normotensive and hypertensive blacks are more apt to have salt-sensitive blood pressure responses to the challenge of a salt load than whites. Moreover, salt sensitivity of blood pressure in both normotensive and hypertensive subjects is associated with a decreased excretory capacity for sodium, implicating the kidney in this phenomenon. Salt sensitivity of blood pressure also is associated with increasing age and, in normotensive subjects, may predict the subsequent development of hypertension. Radical differences in a variety of humoral as well as hemodynamic responses to physical and mental stressors have been identified. The relationships between these observations and renal sodium handling require further investigation.

Black People↗
PubMed1993

Evaluation of diagnostic tests in the differential diagnosis of primary aldosteronism: unilateral adenoma versus bilateral micronodular hyperplasia.

Effective management of primary aldosteronism is dependent upon correct localization of excessive aldosterone production. We report our results of localization studies in patients with biochemically and pathologically confirmed primary aldosteronism. Retrospective chart review identified 69 patients with unilateral adrenal adenoma and 11 with adrenal hyperplasia. Correct unilateral versus bilateral localization of excessive aldosterone production was predicted in 70% versus 71%, respectively, by adrenal venography, 100% versus 63% by adrenal vein hormone sampling, 46% versus 56% by adrenal nuclear scanning and 69% versus 13% by anomalous postural decline of aldosterone. Adrenal computerized tomography appeared to localize correctly 86% versus 80% of the lesions. Unilateral adrenalectomy normalized blood pressure in 79% of the patients with unilateral adenomas versus only 18% of those with adrenal hyperplasia. Once primary aldosteronism is confirmed, localization by adrenal vein sampling, adrenal venography and adrenal computerized tomography is most effective in directing antihypertensive therapy.

Adenoma↗