Nitric oxide-mediated dilation of arterioles to intraluminal administration of aldosterone.
The nature of the rapid action of aldosterone on blood vessels, whether endothelium-dependent dilation or smooth muscle-dependent constriction is predominant, is still in dispute. In this study, we administered aldosterone intraluminally or extraluminally to isolated mesenteric and cerebral arterioles of male Wistar rats. Extraluminal administration of aldosterone (10(-11) or 10(-7) M) elicited a transient vasodilatation. The peak response appeared at approximately 5 minutes. In contrast, intraluminal administration of aldosterone elicited a greater and sustained dilation. When aldosterone (10(-12)-10(-7) M) was administered extraluminally in a cumulative manner, dose-dependent vasodilator responses were elicited, except a reduced dilation was observed to 10(-7) M aldosterone. The dilations were significantly inhibited by spironolactone (10(-7) M), a mineralocorticoid receptor antagonist or Nomega-nitro-l-arginine methyl ester (3 x 10(-4) M), a NO synthesis inhibitor. In endothelium-denuded vessels, extraluminal aldosterone induced a dose-dependent vasoconstrictor response. Scavenging superoxide with Tempol (10(-4) M) sustained the extraluminal aldosterone (10(-11) or 10(-7) M)-induced dilation, whereas inhibition of NO synthesis or removal of the endothelium abolished intraluminal aldosterone-induced dilation. Dilation to 10(-7) M aldosterone was significantly enhanced after inhibition of NAD(P)H-oxidase with apocynin (10(-5) M). Furthermore, in the presence of endothelial dysfunction, induced by chronic inhibition of NO synthesis, intraluminal administration of aldosterone failed to dilate the arterioles. We conclude that in physiological conditions, acute elevation of aldosterone will evoke mainly an endothelium-dependent NO-mediated dilation.
Heylen
Erwan
E
Department of Physiology, New York Medical College, Valhalla, NY 10595, USA.
Huang
An
A
Sun
Dong
D
Kaley
Gabor
G
D000098:Acetophenones / Q000494:pharmacology; D000109:Acetylcholine / Q000494:pharmacology; D000450:Aldosterone / Q000008:administration & dosage* / Q000494:pharmacology*; D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000502:physiology*; D054022:Cerebrum / Q000098:blood supply; D003497:Cyclic N-Oxides / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008643:Mesentery / Q000098:blood supply; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013113:Spin Labels; D013148:Spironolactone / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
D000098:Acetophenones; D003497:Cyclic N-Oxides; D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D013113:Spin Labels; D013481:Superoxides; D009599:Nitroprusside; D013148:Spironolactone; D009569:Nitric Oxide; D000450:Aldosterone; C056165:acetovanillone; D019255:NADPH Oxidases; D000109:Acetylcholine; C001803:tempol; D019331:NG-Nitroarginine Methyl Ester