EFFECTS OF NIFEDIPINE, 8-(N,N-DIETHYLAMINO)OCTYL-3,4,5-TRIMETHOXYBENZOATE HYDROCHLORIDE AND ATRIAL-NATRIURETIC-PEPTIDE ON ENDOTHELIN-INDUCED ANTINATRIURESIS IN DOGS

Nifedipine, 8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate hydroch loride (TMB-8) or atrial natriuretic peptide (ANP) was infused into th e renal artery before and during intrarenal arterial infusion of endot helin-1 (ET) in anesthetized dogs. Before ET infusion, nifedipine (0.1 mug kg-1 min-1), TMB-8 (75 mug kg-1 min-1) or ANP (10 ng kg-1 min-1) increased the urine flow rate, urinary sodium excretion and fractional sodium excretion with little change in renal blood flow or glomerular filtration rate. ET (2 ng kg-1 min-1) reduced the basal renal blood f low, glomerular filtration rate, urine flow rate, urinary sodium excre tion and fractional sodium excretion. Both nifedipine and TMB-8 induce d natriuresis during ET infusion; but only TMB-8 completely reversed t he ET-induced reduction in fractional sodium excretion and partially a ntagonized the reductions in urine flow rate and urinary sodium excret ion. ANP did not induce substantial urinary responses during ET infusi on. Neither nifedipine, TMB-8 nor ANP reversed the ET-induced decrease s in renal blood flow and glomerular filtration rate. The present stud y suggests that in the dog kidney 1) the ET-induced antinatriuresis is caused in part by enhancement of tubular sodium reabsorption, 2) the tubular action of ET depends on TMB-8-sensitive calcium movements but not calcium influx through dihydropyridine-sensitive channels and 3) A NP cannot counteract the ET-induced antinatriuresis.