Altered Serotonin Receptor Subtypes Mediate Coronary Microvascular Hyperreactivityin Pigs With Chronic Inhibitionof Nitric Oxide Synthesis

Autor: Akira Takeshita, Kouichi Kuwata, Yoshihiro Fukumoto, Katsuo Sueishi, Takeshi Kuga, Hiroshi Yasutake, Kensuke Egashira, Hiroaki Shimokawa, Toshiaki Kadokami, Toshiyuki Kozai
Rok vydání: 1996
Předmět:
Zdroj: Circulation. 94:182-189
ISSN: 1524-4539
0009-7322
DOI: 10.1161/01.cir.94.2.182
Popis: Background We previously reported that chronic inhibition of nitric oxide synthesis by administration of N ω -nitro- l -arginine methyl ester (L-NAME) causes microvascular hyperreactivity to 5-hydroxytryptamine (5-HT) and vascular structural changes in pigs in vivo. In the present study, we investigated the relative contributions of 5-HT receptor subtypes to microvascular hyperreactivity in this animal model. Methods and Results Coronary vasomotor response was studied in 16 pigs treated with oral L-NAME for 4 weeks (L group) and in 11 control pigs (C group). Intracoronary administration of 5-HT at 30 μg/kg decreased coronary blood flow (CBF) in the two groups. The decrease in CBF by 5-HT was greater ( P 2 antagonist. In contrast, the augmented decrease in CBF by 5-HT in the L group was only partly inhibited by ketanserin alone and was blocked completely by ketanserin and methiothepin, a 5-HT 1 /5-HT 2 antagonist. The decrease in CBF caused by prostaglandin F 2α and the increase in CBF caused by nitroglycerin were comparable between the two groups and were not affected by the 5-HT antagonists. Conclusions These results suggest that the 5-HT–induced microvascular hyperreactivity may be mediated by relative changes in affinity for 5-HT receptors or de novo expression of 5-HT 1 receptors in microvascular smooth muscle cells in our animal model.
Databáze: OpenAIRE