Multiple effects of calcium entry blockers on renal function in hypertension.

Abstract

SUMMARY Characterization of the renal effects of calcium entry blockers has not been easy because the inhibition of Ca 2+ cellular influx alters several regulatory functions. The ability of calcium blockers to dilate renal vasculature and to increase glomerular filtration rate is largely determined by the preexisting vascular tone. However, the increments in sodium excretion could occur without alterations in renal hemodynamics. Calcium blockers could increase sodium excretion by inducing a redistribution of renal blood flow toward juxtamedullary nephrons, by inhibiting tubuloglomerular feedback responses, or by a direct action on the tubular transport of sodium. These effects are poorly understood at present. In vitro studies show that the blockade of calcium entry enhances renin secretion and decreases prostaglandin synthesis. This dissociation has not been found during longterm administration, which has been proved to be effective for the treatment of essential hypertension with normal maintenance of renal function. In this respect, there are reports indicating that calcium blockers are particularly effective in a subgroup of patients with essential hypertension who exhibit subtle but detectable alterations in calcium metabolism. Further studies are needed to determine whether this significant response to calcium blockers is due to correction of an early defect of calcium cellular kinetics that initiated the increase in blood pressure. (Hypertension 10: 140-151, 1987) KEY WORDS • glomerular filtration rate blood flow • glomerular mesangium renin-angiotensin-prostaglandin system * renal C ALCIUM entry blockers are relatively new drugs that are gaining rapid acceptance for the treatment of hypertension. '" 3 In fact, their potent properties for relaxing smooth muscle 4 could well account for their efficacy in lowering the increase of total peripheral resistance in patients with hypertension. 5 However, a fundamental concept implicit in the evaluation of any antihypertensive drug is related to its effect on renal function 6 because a decrease in renal perfusion pressure induces several compensatory reac-

The antihypertensive mechanism of verapamil. Alteration of glomerular filtration rate regulation.

“…" 29 This response is what would be expected if the primary effect of verapamil were reduction in preglomerular vascular resistance. If filtration rate were measured in patients shortly after the start of verapamil treatment, an increase in GFR might be observed if the acute hypotensive effects of the calcium entry blocker were prevented; in several studies in patients, increases in GFR have been reported soon after the start of treatment with the calcium entry blocker.…”

Inhibition of human mesangial cell proliferation by calcium channel blockers.

“…8 They have also been shown to reduce the extent of aortic atherosclerosis in cholesterol-fed rabbits. 9 Within the kidney, calcium channel blockers can vasodilate afferent arterioles 10 and might increase the glomerular ultrafiltration coefficient, which is determined in part by mesangial cell function. In patients with hypertension and renal insufficiency, short-term treatment with calcium channel blockers has been shown to improve glomerular filtration rate.…”

Abnormal renal responses to calcium entry blockade in normotensive offspring of hypertensive parents.

“…8 - 10 In addition, diuresis and natriuresis are typically associated with the renal vasodilation induced by these drugs when administered to hypertensive subjects. 11 Furthermore, recent studies have shown that the renal vasculature of normotensive relatives of hypertensive patients is abnormally sensitive to the dilating effect of intrarenally infused diltiazem. 12 Taking these findings into account, we studied the renal responses to an acute oral administration of the calcium entry blocking agent nifedipine in young normotensive subjects with or without one hypertensive parent.…”