Natriuretic Effects of Calcium Antagonists

Summary

An important characteristic which distinguishes calcium antagonists from traditional vasodilators is their natriuretic rather than antinatriuretic action. Evidence that all classes of calcium antagonists have a natriuretic effect has been provided by intravenous administration in animal experiments.

After single oral doses, all calcium antagonists have some natriuretic effect, but its extent differs with different compounds; dihydropyridines have a greater immediate natriuretic response than verapamil or gallopamil. Recent experiments by our group using the newer dihydropyridine derivative, isradipine, indicate that the natriuretic response may occur at even lower doses than the antihypertensive effect. Indeed, doses of 2.5mg, 5.0mg and 7.5mg of this compound caused an increasingly larger fall in blood pressure, while the natriuretic and diuretic effects peaked with the 2.5mg dose. The natriuretic effect is associated with no or a very small change in glomerular filtration rate and with a more consistent increase in renal plasma flow.

The duration of the natriuretic action of calcium antagonists is debated. Our studies have shown that this action is evident during the first 2 days of administration of a dihydropyridine, and then seems to disappear; however, a small negative sodium balance persists, an observation that accounts for the absence of any increase in bodyweight or fluid volumes with long term administration of calcium antagonists, despite their vasodilating action. Recent data have shown that under long term treatment with isradipine sodium clearance was still increased a few hours after administration.

In conclusion, the persistent natriuretic action of calcium antagonists is capable of maintaining a negative sodium balance and, therefore, is likely to contribute to the long term antihypertensive effect of calcium antagonists, which is primarily due to the vasodilation properties of these compounds.