Antihypertensive Drugs and Sodium Restriction: Analysis of Their Interaction Based on Pressure-Natriuresis Relationship

Abstract

The hypotensive effects of some antihypertensive drugs are augmented under sodium restriction, while those of others are not. The mechanisms of these interactions were theoretically analyzed based on the arterial pressure-natriuresis relationship. Four-week studies were performed in 24 patients with essential hypertension who were given a regular sodium diet (12-15 g of NaCl/d) in the first and third weeks and a sodium-restricted diet (1-3 g/d) in the second and fourth weeks. One of three antihypertensive drugs, 60 mg/d of nicardipine (Ca-antagonist), 120 mg/d of propranolol (beta-blocker) or 150 mg/d of captopril (converting-enzyme inhibitor) was administered in the third and fourth weeks. The mean arterial pressure and urinary sodium excretion were measured on the last three days of each week. The degree of interaction between the antihypertensive drugs and sodium restriction was statistically compared. The hypotensive effect of nicardipine and propranolol did not differ with the change in sodium intake, whereas that of captopril was greater under sodium restriction than under the regular sodium diet. Urinary sodium excretion was plotted on the ordinate as a function of arterial pressure before and after administration of the antihypertensive drugs. The pressure-natriuresis curve was shifted left, without a change in the slope, by nicardipine and propranolol and also left, but with a decrease in the slope, by captopril. The hypotensive effect of nicardipine and propranolol, being independent of the amount of sodium intake, was based on the leftward shift of the pressure-natriuresis curve that was probably due to the decrease in renal vascular resistance.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of the Dietary Approaches to Stop Hypertension (DASH) Diet on the Pressure-Natriuresis Relationship

“…5 Antihypertensive agents other than diuretics did not enhance the slope of the curve, but shifted the curve leftward to lower the BP level. 5,8 Similar to the findings with the DASH diet, diuretics had greater BP-lowering effects in patients whose slopes were depressed and sodium sensitivity was high, 5 such as with hypertensives or African Americans. Because the DASH diet is rich in fruits, vegetables, and low-fat dairy foods, 1,10 it contains high amounts of potassium and calcium.…”

“…The finding of increased slope and constant x-intercept remained for the overall group (x-intercept: 91.2Ϯ0. 8 (Figures 1 and 2).…”

“…[11][12][13] To compare the major characteristics of the curve, namely, shift of the curve along the arterial pressure axis and steepness of the curve, between control and DASH diets as well as between subgroups, the extrapolated x-intercept (mm Hg) and the slope ([mmol/ d]/mm Hg) were calculated from the regression lines. 7,8,14,15 …”

“…2 Effects of different types of antihypertensive agents, including angiotensin-converting enzyme inhibitors, ␤-blockers, calcium antagonists, and diuretics, on the pressure-natriuresis curve are also known. 5,6,8 In this article, we studied the effect of the DASH diet on the pressure-natriuresis relationship to clarify the mechanisms of its BP-lowering action. …”

Pathophysiology of Antihypertensive Therapy with Diuretics

“…In other words, the patients are sodium-insensitive. By contrast, as hypertension progresses from moderate to severe, the pressure-natriuresis curve is gradually shifted further rightward and its slope gradually decreases, resulting in higher sodium sensitivity of BP (23)(24)(25). Taken together, this natural history of the pressure-natriuresis curve for essential hypertension and the above-mentioned effect of diuretics on the pressure-natriuresis curve clearly show the indication of diuretics on hypertension (6,26).…”