DOPAMINE AND DILTIAZEM-INDUCED NATRIURESIS IN THE SPONTANEOUSLY HYPERTENSIVE RAT

Dopamine and diltiazem-induced natriuresis in the spontaneously hypert ensive rat. Am. J. Physiol. 273 (Regulatory Integrative Comp. Physiol. 42): R317-R323, 1997.-An attenuated natriuretic response to dopamine and D-1 agonists in genetic hypertension has been attributed to an unc oupling of the renal D-1 dopamine receptor from its G protein-effector protein complex. We have reported that in normotensive Wistar-Kyoto ( WKY) rats the natriuresis induced by calcium channel blockers is cause d in part by activation of renal D-1 dopamine receptors. We tested the interaction between the renal D-1 receptor and a calcium channel bloc ker, diltiazem, infused into a renal artery of anesthetized spontaneou sly hypertensive rats (SHR) acutely loaded with 5% saline. Diltiazem p roduced a 50% increase in renal blood flow and nearly tripled absolute and fractional sodium excretion; urine flow rate more than doubled, b ut glomerular filtration rate did not change. However, the DL receptor antagonist SKF-83742, which had no effect by itself, did not diminish the response to diltiazem. In a separate group of concurrent experime nts, we found that the diltiazem-induced natriuresis was associated wi th a decrease in Na+-K+-adenosinetriphosphatase activity in the renal medulla of SHR. In contrast, in WKY rats, no changes were noted in the renal medulla but a decrease in Na+-K+-adenosinetriphosphatase activi ty was noted in the renal cortex. Diltiazem had no effect on urinary d opamine excretion in either rat strain. We conclude that diltiazem ind uces natriuresis differently in SHR and WKY rats; it is independent of D-1 receptors in SHR and is in great part mediated by renal hemodynam ic, rather than by cortical tubular, effects. These studies support pr evious findings of a defective renal cortical tubular D-1 mechanism in SHR.