Endothelium-derived relaxing factor released by 5-HT: distinct from nitric oxide in basilar arteries of normotensive and hypertensive rats.
1. The role of the endothelium in cerebrovascular responses to 5-hydroxytryptamine (5-HT) was investigated in spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY) in vitro. 2. Cumulative addition of 5-HT caused concentration-dependent contractions in ring preparations of SHR basilar arteries; the contractile response was smaller in WKY basilar arteries. 3. Removal of the endothelium enhanced markedly the contractile responses to 5-HT in WKY arteries but had only a slight effect in SHR arteries. The responsiveness to 5-HT in WKY arteries after removal of endothelium was comparable to that in SHR arteries. 4. The endothelium-dependent relaxation induced by acetylcholine in WKY basilar arteries was almost abolished by treatment with 10 microM methylene blue or 10 microM NG-nitro-L-arginine (L-NOARG). However, the response to 5-HT was not affected by treatment with methylene blue, L-NOARG or indomethacin. 5. Application of 10-20 mM K+ or 3.2 mM tetraethylammonium (TEA) did not change significantly, or only increased slightly, the resting tension, but markedly enhanced the contractile response to 5-HT in WKY arteries with endothelium. In contrast, the submaximal response to 5-HT in SHR arteries with endothelium was significantly enhanced by 0.3 mM TEA. 6. In the presence of 1 mM TEA, the application of 10 microM L-NOARG further enhanced the responses of 5-HT in WKY arteries with endothelium. In SHR arteries with endothelium, 10 microM L-NOARG per se enhanced slightly but significantly the responses to 5-HT. 7. These results indicate that 5-HT-induced contraction in basilar arteries is substantially attenuated by an endothelium-dependent mechanism in WKY, but to a much lesser extent in SHR. The major relaxing factor released by 5-HT from endothelium in WKY is distinct from NO and may exert its effect by activating K+ channels.
Yokota
Y
Y
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Nagoya, Japan.
Imaizumi
Y
Y
Asano
M
M
Matsuda
T
T
Watanabe
M
M
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001488:Basilar Artery / Q000187:drug effects / Q000378:metabolism*; D002560:Cerebrovascular Circulation / Q000187:drug effects; D004730:Endothelium, Vascular / Q000502:physiology; D006973:Hypertension / Q000378:metabolism*; D008297:Male; D008751:Methylene Blue / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism*; D019335:Nitroarginine; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012701:Serotonin / Q000494:pharmacology*
D019335:Nitroarginine; D009569:Nitric Oxide; D012701:Serotonin; D001120:Arginine; D008751:Methylene Blue