Harriet P. Dustan

Inhibition of Angiotensin-Converting Enzyme in Renal-Transplant Recipients with Hypertension

HYPERTENSION has a high prevalence among recipients of renal allografts.1 , 2 Such post-transplantation hypertension may contribute3 , 4 to the high mortality from atherosclerotic vascular disease ...

Obesity-related hypertension: Evaluation of the separate effects of energy restriction and weight reduction on hemodynamic and neuroendocrine status☆

PURPOSE Although weight reduction generally lowers blood pressure, it is unclear whether the response is due to concurrent dietary changes or to reduced body mass itself. In this study, the independent effects of energy restriction and weight reduction were examined prospectively in 24 obese, hypertensive, normoglycemic women whose dietary intake was tightly controlled. SUBJECTS AND METHODS Sodium, potassium, and calcium intake, the polyunsaturated/saturated fat ratio, and the proportional composition of carbohydrate, fat, and protein were constant throughout the 5-month protocol. Hemodynamic and neuroendocrine status was evaluated in four 10-day hospital phases: two prior to weight loss (energy balance and then 800-kcal intake), and two after an average loss of 13 kg to normal body weight (800 kcal and then return to energy balance). RESULTS Fasting serum insulin, triiodothyronine:reverse triiodothyronine ratio, resting metabolic rate, and heart rate declined, and sodium and potassium balances were negative during energy restriction. Catecholamines, renin, aldosterone, plasma volume, cardiac output, and blood pressure showed no consistent response to changes in energy intake. By contrast, weight reduction independently lowered blood pressure, plasma volume, cardiac output, and plasma renin activity. Body fat pattern remained unchanged. CONCLUSION These results demonstrate that weight loss has a blood pressure-lowering effect that is distinct from energy restriction and that is related to changes in blood volume and cardiac output.

Obesity and hypertension in blacks

SummaryIn the United States, obesity and hypertension are more common in blacks than in whites, but that general statement hides some important sex differences. Thus, in black women the prevalences of both obesity and hypertension are greater than in white women, whereas in men, although there is no racial difference in obesity, in blacks hypertension is more common and more severe than in whites. For white people, there is a well-documented causal relationship between obesity and hypertension, however, results from the second National Health and Nutrition Examination (NHANES II) suggest that this relationship is not so strong for blacks. Obesity is also an important risk factor for diabetes, which in itelf is associated with hypertension. The mechanisms of obesity-associated hypertension appears to be an inadequate vasodilation in the face of the increased blood volume and cardiac output, which are the natural consequences of an increased body mass. This defect in control of vascular resistance has been attributed to increased activity of the sympathetic nervous system, abnormal reninangiotensin-aldosterone relationships, and insulin resistance. However, none of these attributes has been found to be the exclusive characteristic of obese hypertensive as compared with normotensive obese subjects.

Enalapril in low‐renin essential hypertension

The antihypertensive efficacy of N‐[(S)‐I‐(ethoxycarbonyl)‐3‐phenyl‐propyl]‐L‐alanyl‐L‐proline (enalapril maleate) was evaluated in a randomized, double‐blind trial in 23 patients with mild low‐renin essential hypertension ranging in age from 32 to 70 yr (20 were black and 3 were white). All underwent a 4‐wk washout‐placebo phase and were then assigned to a dosing schedule of either 10 mg enalapril once daily, 5 mg enalapril twice daily, or placebo twice daily for 12 wk. Conditional on diastolic pressure, the dose was increased at 4‐wk intervals to a maximum of 40 mg daily or until control was achieved or the end of the study reached. At the end of the 12‐wk titration phase, there was a follow‐up period during which measurements were made after discontinuation of the medication. Mean supine diastolic pressure decreased from baseline (98.5 ± 2.6 mm Hg) during the titration phase (86.3 ± 4.6 mm Hg) in the group taking enalapril once daily. In three of the eight patients in the once‐daily group and five of eight in the twice‐daily group, supine diastolic pressures fell below 90 mm Hg. Neither supine nor standing systolic pressure nor standing diastolic pressure decreased significantly from pretreatment levels during enalapril once or twice daily. Heart rates measured after 5 min supine rest were not altered by enalapril. Enalapril induced inhibition of converting enzyme activity at all dose levels and with both dosing schedules. No adverse effect attributable to enalapril occurred during the study. The data indicate that once‐daily enalapril is safe and effective treatment for mild low‐renin essential hypertension.

Relationship of Sodium Balance to Arterial Pressure in Black Hypertensive Patients

To investigate the quantitative importance of sodium balance to arterial pressure changes produced by changes in sodium intake, we studied normotensive white and black subjects and hypertensive black patients with two protocols. Protocol 1 used a 3-day control period with a 150 mEq sodium intake/day followed by 4 days of salt depletion (SD) with a diet providing 9 mEq/day of sodium and furosemide, 1 mg/kg, given the first day and then 3 days of salt loading (SL), during which 25 mL/kg of isotonic sodium chloride solution was given intravenously each day (3.88 mEq sodium/kg/day). In protocol 2, the sequence of sodium intake changes was reversed. For both protocols, sodium balance was calculated by subtracting urinary sodium excretion from sodium intake and expressed in mEq/kg, either positive or negative. In protocol 1, the hypertensives had statistically significant changes in arterial pressure with changes in salt intake, and they also lost more sodium than normotensives during SD. In protocol 2, blacks, both normotensives and hypertensives, had statistically significant pressure changes with both SL and SD, and black hypertensives retained less sodium during SL than either normotensive group. Spearman correlations showed no relationship between sodium balance and mean arterial pressure, suggesting that salt-sensitive hypertension results not from the magnitude of sodium retention, but from the pressor mechanisms evoked.

Lofexidine and clonidine in moderate essential hypertension

The efficacy, safety, and tolerability of lofexidine, a centrally acting imidazoline derivative, were compared to that of clonidine in a randomized double‐blind trial in 28 patients with moderate essential hypertension. The study consisted of a washout phase, a placebo phase, a drug titration phase (0.2 to 1.6 mglday, with hydrochlorothiazide added at 0.4 mg daily for supine and erect diastolic blood pressure above 90 mm Hg), and a maintenance phase lasting 3 mo. During the titration phase supine systolic and diastolic pressures fell in lofexidine patients from 143 ± 4198 ± 3 to 122 ± 3181 ± 2 mm Hg and in clonidine patients from 154 ± 61101 ± 2 to 124 ± 4/81 ± 2 mm Hg (P < 0.01), and erect systolic and diastolic pressures fell in lofexidine patients from 143 ± 31105 ±2 to 116 ± 3185 ± 2 mm Hg and in clonidine patients from 156 ± 6/104 + 2 to 117 ± 4/82 ± 2 mm Hg (P < 0.01). Maximal doses of lofexidine and clonidine in combination with hydrochlorothiazide had equivalent antihypertensive effects, but when the effects of lofexidine and clonidine were compared at each dose level, larger doses of lofexidine were needed to control blood pressure. There was no change in heart rate in lofexidine patients in either the supine or erect position during the titration phase but heart rate fell in the clonidine patients (P < 0.05) over the same period. Dry mouth and drowsiness were reported in both groups but were both less frequent and less severe in the lofexidine group than the clonidine group.

Treatment of obesity-associated hypertension

Many obese people are hypertensive either because of obesity-associated hypertension or because the two conditions coexist. Weight loss is recommended for all obese hypertensives as some patients benefit by concomitant reductions of arterial pressure and/or decreased requirements for antihypertensive drugs. Since obesity-associated hypertension cannot be diagnosed as a separate entity, available evidence was reviewed to determine the antihypertensive effectiveness of weight loss and effects of weight loss on antihypertensive drug requirements. Generally speaking, patients with mild hypertension appear to respond better to weight reduction than those with moderate and severe hypertension. However, a substantial percentage of patients with mild hypertension may be unresponsive. Weight loss also seems to have potential for lessening requirements for antihypertensive drug therapy. Beneficial effects for both blood pressure and drug requirements are due to weight loss and not caloric restriction, per se. Mechanisms of the beneficial effects are related to consequences of weight loss and appear to involve decreased cardiac output and blood volume. The issue of salt sensitivity of obesity-associated hypertension is unresolved.

Measurement of effective renal plasma flow in congestive heart failure

In the management of patients with congestive heart failure (CHF), it is often desirable to have precise knowledge of overall renal function, including the effective renal plasma flow (ERPF). It has long been recognized that ERPF is diminished in CHF. Since glomerular filtration rate is often decreased to a much lesser extent, other noninvasive procedures such as the measurement of creatinine clearances may not be entirely suitable. ERPF determination by the single plasma sampling (SPS) method affords a rapid, simple, noninvasive, and economical technique that is quite accurate and reproductible. A SPS method has been well-tested in patients following renal transplantation plus a wide variety of nephrological disorders. We have been concerned whether the SPS method would be valid in volume expanded patients.In 28 determinations of ERPF in patients with CHF, and in five patients who did not have CHF, we have found the SPS estimation of ERPF to yield results that are not clinically significantly different from those obtained by the detailed compartmental analysis method. The volumes of 131I-orthoiodohippurate (OIH) distribution were found to be somewhat higher in CHF than in controls, but fractional rate constants were proportionately lower so that intercompartmental flow rates and OIH concentrations were not different from controls. Therefore, the SPS estimation of ERPF is valid in patients with CHF and may be useful in monitoring the renal effects of various hemodynamic and pharmacological interventions.