The Diuretic Effect of Calcium Entry Blockade in Normals and Hypertensive Patients.

Abstract

Calcium entry blockers have been shown to exert hemodynamic and diuretic effects in the kidney. The diuretic effects can be demonstrated most clearly in the isolated perfused kidney, not influenced by compensatory mechanisms such as a lower blood pressure or changes of hormones. However, they can also be shown in vivo in humans. We studied the renal effects of calcium entry blockade after the first dosage and after continued oral dosages of 20 mg nicardipine tid in patients with essential hypertension and in normotensive controls. Renal function was determined during maximal free water clearance, allowing estimation of changes in "proximal" and "distal" tubular sodium reabsorption . Results showed a natriuretic effect. In the control subjects, clearance results were compatible with a decrease of proximal and distal tubular reabsorption, but in the hypertensive group natriuresis was mainly achieved by an increase of the glomerular filtration rate and a decrease of fractional distal reabsorption. In both groups the natriuresis occurred concomitantly with a lower blood pressure. The ratio plasma renin activity/plasma aldosterone concentration increased, although nicardipine did not inhibit the increase of plasma aldosterone during angiotensin II infusion. Pre-treatment with the calcium entry blocker nitrendipine enhanced the natriuretic effect of atrial natriuretic factor (ANF) in sodium replete normal volunteers. Facilitation of sodium excretion by human ANF may be an additional diuretic mechanism of calcium entry blockers.atrial natriuretic factor ; calcium entry blockade ; diuretic ; nicardipine ; sodium excretion Calcium entry blockade has been shown to exert diuretic effects. This occurs in the perfused kidney, isolated from influences of hormones and changes of arterial pressure, as well as in vivo in experimental mammals and man (Luft 1987). Despite abundant experimental demonstration of this effect, no single or principal mechanism has as yet been demonstrated. Evidence has indeed accumulated that the sodium and water excretion during calcium entry blockade has multiple causes, which even may vary among the many drugs of this class. For instance, only verapamil and diltiazem have been shown to decrease the short

Calcium channel blockers: pharmacology and place in therapy of pediatric hypertension

“…For example, as mentioned above, short-term administration of felodipine has been demonstrated to both increase and decrease natriuresis and diuresis, depending on the dose administered [44]. However, most reports have indicated that patients maintained on CCBs for chronic therapy exhibited increases in sodium and water excretion that may contribute to their antihypertensive effects [69,70].…”