Chronic administration of a tyrosine kinase inhibitor restores functional and morphological changes of the basilar artery during chronic hypertension

Jiro Kitayama, Takanari Kitazono, Hiroaki Ooboshi, Tetsuro Ago, Tetsuya Ohgami, Masatoshi Fujishima, Setsuro Ibayashi

研究成果: Contribution to journalArticle査読

14 被引用数 (Scopus)

抄録

Objective: Activation of tyrosine kinase appears to play an important role in pathogenesis of cardiovascular disease during chronic hypertension. In the present study, we tested the hypothesis that long-term treatment with an inhibitor of tyrosine kinase would have beneficial effects on hypertension-induced morphological and functional changes of the cerebral artery. Methods: Male spontaneously hypertensive rats (SHR; 4 months old) were fed normal rat chow, or that containing an inhibitor of tyrosine kinase, genistein (1 mg/kg chow). Normotensive Wistar-Kyoto (WKY) rats were also fed either of the chows. After feeding the rats for 2 months, we measured wall thickness, diameter of the basilar artery and its dilator responses to acetylcholine (ACh); Y-26763, an opener of ATP-sensitive potassium channels; and Y-27632, an inhibitor of Rho-associated kinase. Results: Treatment with genistein did not cause significant changes in physiological variables, including mean arterial pressure in either strain. In control SHR, the wall thickness of the basilar artery was greater than that of WKY rats. Genistein treatment reduced the wall thickness significantly in SHR. Vasodilator responses induced by ACh and Y-26763 were markedly attenuated in SHR compared to WKY rats, and treatment of SHR with genistein significantly improved the vasodilatation. Dilatation of the artery in response to Y-27632 was enhanced in SHR compared to WKY rats and treatment of SHR with genistein did not affect the enhanced vasodilator responses to Y-27632. Conclusions: Chronic treatment with genistein may be a novel approach to prevent cerebrovascular disorders.

本文言語英語
ページ(範囲)2205-2211
ページ数7
ジャーナルJournal of hypertension
20
11
DOI
出版ステータス出版済み - 11 2002

All Science Journal Classification (ASJC) codes

  • 内科学
  • 生理学
  • 循環器および心血管医学

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