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

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)2205-2211
Number of pages7
JournalJournal of hypertension
Volume20
Issue number11
DOIs
Publication statusPublished - Nov 1 2002

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Basilar Artery
Genistein
Protein-Tyrosine Kinases
Inbred WKY Rats
Hypertension
Vasodilator Agents
Acetylcholine
Cerebrovascular Disorders
rho-Associated Kinases
KATP Channels
Cerebral Arteries
Inbred SHR Rats
Vasodilation
Dilatation
Arterial Pressure
Cardiovascular Diseases
Arteries
Y 27632

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Chronic administration of a tyrosine kinase inhibitor restores functional and morphological changes of the basilar artery during chronic hypertension. / Kitayama, Jiro; Kitazono, Takanari; Ooboshi, Hiroaki; Ago, Tetsuro; Ohgami, Tetsuya; Fujishima, Masatoshi; Ibayashi, Setsuro.

In: Journal of hypertension, Vol. 20, No. 11, 01.11.2002, p. 2205-2211.

Research output: Contribution to journalArticle

Kitayama, Jiro ; Kitazono, Takanari ; Ooboshi, Hiroaki ; Ago, Tetsuro ; Ohgami, Tetsuya ; Fujishima, Masatoshi ; Ibayashi, Setsuro. / Chronic administration of a tyrosine kinase inhibitor restores functional and morphological changes of the basilar artery during chronic hypertension. In: Journal of hypertension. 2002 ; Vol. 20, No. 11. pp. 2205-2211.
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