Role of renal dopamine D1 receptors in natriuresis induced by calcium channel blockers.
The direct tubular natriuretic effect of calcium channel blockers (CCBs) may be due to an interaction between CCBs and a renal tubular dopamine receptor. We therefore studied the effects of two chemically unrelated CCBs, diltiazem and isradipine, infused into the right renal artery of 5% saline-loaded anesthetized rats alone or in the presence of a D1 antagonist, SKF-83742. Isradipine (0.03 microgram.kg-1.min-1) or diltiazem (20 but not 10 micrograms.kg-1.min-1) alone produced an increase in urine flow and an approximate doubling of absolute and fractional sodium excretion, which was not seen in the left kidney or in the control animals (analysis of variance, Scheffé's test, P < 0.05). SKF-83742 alone given systemically or into the right renal artery did not affect these parameters but did block the actions of diltiazem or isradipine. There was no change in mean arterial pressure, renal blood flow, or glomerular filtration rate in any of the experiments. In additional studies, we found that a combined infusion of dopamine (0.1 microgram.kg-1.min-1) and diltiazem (10 micrograms.kg-1.min-1) (doses that by themselves did not alter renal function) produced a twofold or greater increase in urine flow and absolute and fractional sodium excretion; glomerular filtration rate was not significantly changed. Intrarenal arterial CCBs, without a change in renal hemodynamics, produce a natriuresis that is blocked by a D1 antagonist. Concomitant administration of diltiazem and dopamine (each in subeffective doses when used alone) produces a synergistic effect.(ABSTRACT TRUNCATED AT 250 WORDS)
Eisner
G M
GM
Department of Medicine and Physiology and Biophysics, Georgetown University Medical Center, Washington, District of Columbia 20007.
Yamaguchi
I
I
Felder
R A
RA
Asico
L D
LD
Jose
P A
PA
D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004110:Diltiazem / Q000008:administration & dosage / Q000494:pharmacology; D004231:Diuresis / Q000187:drug effects; D004298:Dopamine / Q000494:pharmacology; D004347:Drug Interactions; D007261:Infusions, Intra-Arterial; D017275:Isradipine / Q000008:administration & dosage / Q000494:pharmacology; D007668:Kidney / Q000098:blood supply / Q000502:physiology*; D008297:Male; D009318:Natriuresis / Q000187:drug effects*; D051381:Rats; D011921:Rats, Inbred WKY; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors / Q000502:physiology*; D012077:Renal Artery
D001552:Benzazepines; D002121:Calcium Channel Blockers; D017447:Receptors, Dopamine D1; C035674:SK&F 83742; D004110:Diltiazem; D004298:Dopamine; D017275:Isradipine