The antihypertensive effects of calcium channel blockade: role of sodium and calcium metabolism.

To study the relation of calcium channel blockade to sodium and calcium metabolism, we measured blood pressure (BP), serum ionized calcium (Ca-io), plasma renin activity (PRA), and 1,25-dihydroxy-vitamin D (1,25D), before and after administration of nitrendipine to essential hypertensive (EH) outpatients on both low and high dietary salt intakes, and on fixed (10 mg b.i.d.) and titrated dose (10-30 mg b.i.d.) schedules. Nitrendipine lowered BP (% delta DBP = -14.9 +/- 3 vs. 1 +/- 3.5, p less than 0.001) and raised Ca-io (0.08 +/- 0.04 vs. -0.04 +/- 0.05 mEq/L, p less than 0.05) in salt-sensitive (SS) but not salt-insensitive (SI) subjects. % delta DBP was related to PRA (r = 0.69, p less than 0.001), to the rise in Ca-io (r = -0.63, p less than 0.01), and to the suppression of circulating 1,25D (r = 0.80, p less than 0.001). Similarly, at doses (10-30 mg b.i.d.) titrated to achieve normotension, nitrendipine uniformly elevated PRA (1.4 +/- 0.3 to 3.5 +/- 0.7 ng/ml/h, p less than 0.05) and Ca-io (2.34 +/- 0.02 to 2.44 +/- 0.02 mEq/L, p less than 0.05). We conclude that the antihypertensive efficacy of nitrendipine appears greatest among SS and lower renin patients, and is related to the drug's ability to alter calcium metabolism. The state of calcium metabolism may thus underlie the sensitivity to calcium blockade and may contribute to its effects.