Calcium channel blockers reduce blood pressure in part by inhibiting vascular smooth muscle carbonic anhydrase I.

Calcium channel blockers are a group of drugs used for the treatment of hypertension. Carbonic anhydrase (CA) I detected in vascular smooth muscle and in other cells in the organism has a major role in the acid-base balance and in vascular processes. Our previous work has proven that verapamil inhibits CA activity by a direct mechanism of action. Starting from our results in this article we studied in vitro and in vivo the effect of calcium channel blockers (verapamil and amlodipine) on erythrocyte CA I, on vascular smooth muscles CA I, and on arterial blood pressure values in human and in animals. Our in vitro and in vivo results have proved that verapamil and amlodipine are strong CA I inhibitors both in human erythrocytes and also in vascular smooth muscles in animals. In humans, calcium channel blockers studied here progressively reduce arterial blood pressure in hypertensive subjects, in parallel with progressive lowering of erythrocyte CA I activity in the normal range in normotensive subjects. From our point of view verapamil and amlodipine possess a dual mechanism of action: the first well-known action consists of their action on calcium channels. The second mechanism, suggested by us, directly acts on the vascular smooth muscle CA I isozyme, so that its inhibition should ensure an adequate pH for calcium ions transport through the channels, having as result vasodilation. This double mechanism could explain the hypotensive effect of verapamil and amlodipine, with a mechanism that partially dependent on CA I inhibition.