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 hydrochloride (TMB-8) or atrial natriuretic peptide (ANP) was infused into the renal artery before and during intrarenal arterial infusion of endothelin-1 (ET) in anesthetized dogs. Before ET infusion, nifedipine (0.1 micrograms kg-1 min-1), TMB-8 (75 micrograms 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 flow, glomerular filtration rate, urine flow rate, urinary sodium excretion and fractional sodium excretion. Both nifedipine and TMB-8 induced natriuresis during ET infusion; but only TMB-8 completely reversed the ET-induced reduction in fractional sodium excretion and partially antagonized the reductions in urine flow rate and urinary sodium excretion. ANP did not induce substantial urinary responses during ET infusion. Neither nifedipine, TMB-8 nor ANP reversed the ET-induced decreases in renal blood flow and glomerular filtration rate. The present study 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) ANP cannot counteract the ET-induced antinatriuresis.
Takagi
H
H
Department of Pharmacology, Tohoku University, Sendai, Japan.
Takahara
A
A
Tomura
Y
Y
Yamagata
T
T
Hisa
H
H
Satoh
S
S
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D004285:Dogs; D016232:Endothelins / Q000494:pharmacology*; D005260:Female; D005707:Gallic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D009318:Natriuresis / Q000187:drug effects*; D009543:Nifedipine / Q000494:pharmacology*
D016232:Endothelins; C006014:8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate; D005707:Gallic Acid; D009320:Atrial Natriuretic Factor; D009543:Nifedipine