Effects of the calcium channel antagonist nicardipine on renal action of endothelin in dogs.
Endothelin is a potent vasoconstrictor peptide isolated from cultured vascular endothelial cells. Interaction between endothelin and calcium channel antagonist on the renal hemodynamics and urine formation was studied in anesthetized dogs. Intrarenal arterial administration of the peptide progressively reduced renal blood flow from 139 +/- 22 to 85 +/- 12 ml/min at 20 min after the start of continuous infusion, with no change in systemic blood pressure. Glomerular filtration rate, urine flow and urinary sodium and calcium excretion decreased significantly by 30-50% from the preinfusion control values. An endothelin-induced reduction in renal blood flow was markedly attenuated by pretreatment with the calcium antagonist nicardipine (100 ng/kg/min intrarenally). Changes in glomerular filtration rate and antinatriuretic and anticalciuretic actions by the peptide was not affected by nicardipine treatment. It is suggested that the renal vasoconstrictor action, but not the tubular action, of endothelin is functionally coupled with the activation of dihydropyridine-sensitive calcium channels.
Yukimura
T
T
Department of Pharmacology, Osaka City University Medical School, Japan.
Miura
K
K
Yamashita
Y
Y
Shimmen
T
T
Okumura
M
M
Yamanaka
S
S
Saito
M
M
Yamamoto
K
K
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004285:Dogs; D016232:Endothelins / Q000494:pharmacology*; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007668:Kidney / Q000187:drug effects*; D008297:Male; D009529:Nicardipine / Q000494:pharmacology*; D012079:Renal Circulation / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects
D016232:Endothelins; D009529:Nicardipine