Does renin determine the blood pressure response to calcium entry blockers?

Abstract

SUMMARY Male Wistar rats with one-kidney, one clip renal hypertension were maintained on either a regular or a low salt diet for 3 weeks after clipping. At that time mean blood pressure in the unanesthetized rats was equally elevated in sodium-depleted (n = 17) and in sodium-replete rats (n = 19), but plasma renin activity was significantly higher in the former (p < 0.05). Infusion of the calcium entry blocker verapamll at a rate of 0.05 mg/kg/minute decreased blood pressure within 60 minutes to a similar extent in rats kept on a salt-deficient diet and in rats fed a regular salt diet. In all rats taken as a group, there was a close, direct correlation (r = 0.87, p < 0.001) between the magnitude of the blood pressure response to verapamil and the pretreatment blood pressure levels. Verapamil markedly accelerated heart rate and stimulated renin release in all rats. In additional groups of sodium-depleted (ii = 8) and sodium-replete renal hypertensive rats (n = 7), nifedipine administration (4 /xg/kg/min i.v.) within a 45-minute observation period caused a blood pressure fall (p < 0.001) and heart rate acceleration (p < 0.001) that were comparable in both groups. These findings suggest that in the rat with renal hypertension the short-term blood pressure response to the calcium antagonists verapamil and nifedipine is not influenced by the state of sodium balance and plasma renin activity. In this experimental model of hypertension, the magnitude of the blood pressure lowering effect of calcium entry blockers appears to be proportional to pretreatment blood pressure levels. (Hypertension 7: 223-227, 1985) KEY WORDS • renal hypertension high and low renin levels verapamil • nifedipine * conscious rats D URING recent years numerous studies have focused on the crucial role of intracellular free calcium in determining vascular smooth muscle tone.1 -2 Calcium channel blocking agents have been used to reduce intracellular calcium in an attempt to lower the blood pressure of hypertensive patients. Such drugs have proved to be helpful in managing hypertensive patients and appear particularly effective in reducing blood pressure when the rate of renin secretion is low.3 -4The present investigation was undertaken in conscious hypertensive rats to assess the effect of a change in sodium balance and renin release on the short-term blood pressure response to the calcium entry blockers verapamil and nifedipine. 5 The experiments were car- ried out in rats with hypertension induced by partially occluding one renal artery with the contralateral kidney removed (one-kidney, one clip renal hypertension) maintained postoperatively for 3 weeks on either a saltdeficient or a regular salt intake. As was known from previous work, 6 -7 blood pressure during the phase of established hypertension achieves similar high levels in sodium-depleted and sodium-replete rats in spite of the fact that plasma renin activity is elevated only in the former. Materials and MethodsMale Wistar rats weighing 140 to 180 g (Madorin AG, Fiillinsdorf, Switze...