The role of atrial natriuretic peptide in the diuretic effect of Ca²⁺ entry blockers

The effect of three calcium entry blockers - verapamil, nifedipine and felodipine - on diuresis, natriuresis, the renin-aldosterone axis, and atrial natriuretic peptide (ANP) levels was studied in 30 previously untreated patients with mild to moderate essential hypertension. All three blockers produced significant antihypertensive effects after 2 and after 24 h. Heart rate tended to decrease, but did not change significantly after verapamil, but increased significantly 1-2 h after nifedipine and felodipine. Plasma renin activity (PRA) did not change significantly with any treatment, and plasma aldosterone decreased with all three agents. ANP levels did not change significantly after verapamil, but increased significantly after nifedipine and felodipine. There was a significant positive correlation between the maximal change in ANP level and urinary sodium after nifedipine and felodipine. The increase in urinary sodium after verapamil was not significant. The role of the direct renal effect of calcium entry blockers in their persistent natriuretic action is discussed, as well as their short-term enhancement of ANP levels, which may account for the initial diuretic and natriuretic effects seen with this class of dihydropiridines.