Endothelin modulates L-NG-nitroarginine-induced enhancement of vasoconstriction evoked by norepinephrine.
The interaction of endothelin-1 (ET-1), a novel vasoconstrictor peptide synthesized according to the encoded amino acid sequence, with L-NG-nitroarginine (NOARG), an L-arginine-reversible inhibitor of endothelium-derived relaxing factor (EDRF) on adrenergic receptors, was investigated. Male Sprague-Dawley rats were used in this study. Mesenteric arteries were isolated and perfused with Krebs-Ringer solution at a constant flow rate. The vasoconstrictor responses to exogenous norepinephrine were determined. Low concentrations of ET-1 (10(-11) and 10(-10) M) potentiated the pressor responses to norepinephrine without affecting the baseline perfusion pressure. Simultaneous NOARG (10(-5) M) infusion with ET-1 (10(-11) M) into the mesenteric arteries caused further enhancement of the pressor responses to exogenous norepinephrine (200 ng) without affecting the baseline perfusion pressure: 126 +/- 15% to 262 +/- 45% (p less than 0.05, vehicle control: 100%). This facilitatory effect of NOARG on the pressor response to norepinephrine was attenuated with L-arginine (10(-4) M) infusion, but not D-arginine. These results suggest that ET, one of the endothelium-derived vasoconstricting factors, interacts with EDRF to modulate the tone of resistance vessels.
Tabuchi
Y
Y
Department of Geriatric Medicine, Osaka University Medical School, Japan.
Shi
S J
SJ
Mikami
H
H
Ogihara
T
T
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D004347:Drug Interactions; D016232:Endothelins / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009569:Nitric Oxide / Q000494:pharmacology; D019335:Nitroarginine; D009638:Norepinephrine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011941:Receptors, Adrenergic / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects*
D016232:Endothelins; D011941:Receptors, Adrenergic; D019335:Nitroarginine; D009569:Nitric Oxide; D001120:Arginine; D009638:Norepinephrine