The site of action of nitrendipine in the rat kidney

Ample evidence suggests that Ca2+ antagonists like nitrendipine are capable of inducing mild diuresis and natriuresis in states predisposing to natriuresis, although there is disagreement on common possible sites or mechanisms of action. To clarify this situation, clearance, micropuncture, and microperfusion studies were undertaken on rats to establish whether nitrendipine inhibits sodium and fluid reabsorption in strict hydropenia, and if so, in which nephron segments this occurs. The clearance studies failed to show any specific effect on glomerular filtration rate, urine flow, or sodium excretion; mean arterial blood pressure was, however, dose-dependently depressed. Single nephron filtration rate, measured in the distal tubule, was also not altered, but fractional salt and water reabsorption up to that site were modestly reduced. Since microperfusion studies failed to show any inhibition of thick ascending limb transport, this implies a proximal inhibitory action, a conclusion confirmed by proximal microperfusion studies. Thus, in strict hydropenia, nitrendipine inhibits proximal salt and water reabsorption, but the increased distal load is completely compensated by distal tubular and collecting duct mechanisms such that urinary electrolyte excretion is unaltered.