Role of Na(+)/H(+) exchanger in dilator responses of rat basilar artery in vivo.
We tested the hypothesis that activation of Na(+)/H(+) exchanger is involved in dilator responses of the basilar artery to endothelium-dependent vasodilators in vivo. Using a cranial window in anesthetized rats, we examined responses of the basilar artery to acetylcholine and bradykinin. Topical application of acetylcholine and bradykinin increased diameter of the basilar artery in a concentration-related manner. Because N(G)-nitro-L-arginine, an inhibitor of nitric oxide synthase, almost abolished vasodilator responses to acetylcholine and bradykinin, vasodilatation produced by the agonists appears to be mediated primarily by nitric oxide. 5-N,N-Hexamethyleneamiloride, an inhibitor of Na(+)/H(+) exchanger, did not affect baseline diameter of the basilar artery, but inhibited vasodilatation in response to acetylcholine and bradykinin, without affecting vasodilatation produced by sodium nitroprusside. FR183998, another inhibitor of Na(+)/H(+) exchanger, also attenuated acetylcholine-induced dilatation of the basilar artery without affecting vasodilatation in response to sodium nitroprusside. Monomethylamine hydrochloride, which produces intracellular alkalinization, enhanced acetylcholine-induced dilatation of the basilar artery in the presence of 5-N,N-hexamethyleneamiloride. These results suggest that intracellular alkalinization produced by activation of Na(+)/H(+) exchanger may enhance nitric oxide production in the basilar arterial endothelium and thereby contribute to dilator responses of the artery in vivo.
Kitazono
T
T
Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan. kitazono@intmed2.med.kyushu-u.ac.jp
Kamouchi
M
M
Ago
T
T
Ooboshi
H
H
Nakamura
H
H
Fujishima
M
M
Ibayashi
S
S
D000109:Acetylcholine / Q000494:pharmacology; D000584:Amiloride / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001488:Basilar Artery / Q000187:drug effects / Q000378:metabolism*; D001920:Bradykinin / Q000494:pharmacology; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008744:Methylamines / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
D000970:Antineoplastic Agents; D008744:Methylamines; D017923:Sodium-Hydrogen Exchangers; C057360:5-(N,N-hexamethylene)amiloride; D009599:Nitroprusside; D009569:Nitric Oxide; D000584:Amiloride; C027451:methylamine; D000109:Acetylcholine; D001920:Bradykinin