Altered serotonin receptor subtypes mediate coronary microvascular hyperreactivity in pigs with chronic inhibition of nitric oxide synthesis

Toshiaki Kadokami, Kensuke Egashira, Kouichi Kuwata, Yoshihiro Fukumoto, Toshiyuki Kozai, Hiroshi Yasutake, Takeshi Kuga, Hiroaki Shimokawa, Katsuo Sueishi, Akira Takeshita

    Research output: Contribution to journalArticlepeer-review

    26 Citations (Scopus)

    Abstract

    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<.01) in the L group than in the C group. The decrease in CBF by 5-HT in the C group was blocked completely by pretreatment with ketanserin, a 5-HT2 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-HT1/5-HT2 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-HT1 receptors in microvascular smooth muscle cells in our animal model.

    Original languageEnglish
    Pages (from-to)182-189
    Number of pages8
    JournalCirculation
    Volume94
    Issue number2
    DOIs
    Publication statusPublished - 1996

    All Science Journal Classification (ASJC) codes

    • Cardiology and Cardiovascular Medicine
    • Physiology (medical)

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