Effects of atrial natriuretic peptide on endothelin-induced vasoconstriction and intracellular calcium mobilization.
Mechanisms for the antagonistic action of atrial natriuretic peptide (ANP) toward endothelin were studied. We examined the effects of ANP on endothelin-induced vasoconstriction in isolated perfused kidney and the elevation of intracellular free calcium concentration using Fura-2 in cultured rat vascular smooth muscle cells (VSMC). Endothelin produced an increase in renal vascular resistance in isolated perfused kidney (2 x 10(-10) mol/l, +109%; P less than 0.01). ANP completely abolished renal vasoconstriction induced by endothelin. Endothelin produced a biphasic elevation in intracellular calcium concentration in the VSMC. Ethyleneglycol-bis-(beta-amino-ethylether)-N,N,N',N'-tetr aac etic acid (EGTA; 3 mmol/l) or nicardipine (10(-8) mol/l) decreased the sustained elevation of intracellular calcium concentration by 10(-8) mol/l endothelin to the basal level (endothelin, +15% versus EGTA + endothelin, -1%; P less than 0.05; endothelin, +18% versus nicardipine + endothelin, +5%; P less than 0.01). Pretreatment with 10(-6) mol/l ANP suppressed neither the peak phase of intracellular calcium concentration elevation (endothelin, 10(-8) mol/l, +35% versus endothelin + ANP, +31%; not significant) nor the sustained phase of intracellular calcium concentration elevation (endothelin, 10(-8) mol/l, +21% versus endothelin + ANP, +16%; not significant). ANP markedly increased the production of cyclic 3',5'-guanosine monophosphate (cGMP) in the VSMC (ANP, 10(-6) mol/l, +1100%; P less than 0.01). However, endothelin did not influence cGMP production in the presence or absence of ANP. ANP may antagonize the vasoconstrictive action of endothelin through an effect on the steps subsequent to the mobilization of intracellular calcium in the pathway of vascular smooth muscle contraction.
Suzuki
E
E
Second Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
Hirata
Y
Y
Matsuoka
H
H
Sugimoto
T
T
Hayakawa
H
H
Shin
W S
WS
Toyooka
T
T
Sugimoto
T
T
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004533:Egtazic Acid / Q000494:pharmacology; D016232:Endothelins / Q000037:antagonists & inhibitors*; D066298:In Vitro Techniques; D008297:Male; D009529:Nicardipine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects*
D016232:Endothelins; D004533:Egtazic Acid; D009320:Atrial Natriuretic Factor; D009529:Nicardipine; D002118:Calcium