Mechanisms underlying enhanced vasodilator responses to various vasodilator agents following endothelium removal in rat mesenteric resistance arteries

Yukiko Iwatani, Hiromi Numa, Saori Atagi, Fusako Takayama, Mitsunobu Mio, Hiromu Kawasaki

Research output: Contribution to journalReview article

1 Citation (Scopus)

Abstract

We reported that vasodilator responses to various vasodilator agents were augmented by endothelium removal. To explain this mechanism, we hypothesized that endothelium removal eliminates the release of endothelium-derived contracting factor EDCF, which counteracts the vasodilation. However, the underlying mechanism is unknown. Therefore the present study investigated the second messenger system further to investigate the mechanisms underlying enhanced vasodilator response after endothelium removal in rat mesenteric resistance arteries. Mesenteric vascular beds isolated from Wistar rats were perfused and perfusion pressure was measured. The vascular endothelium was removed by 30-s perfusion of sodium deoxycholate. Vasodilator responses to sodium nitroprusside (SNP) perfusion were markedly augmented and prolonged by endothelium removal. In preparations with intact endothelium and active tone, 5-min perfusion of sodium azide (non-specific guanylate cyclase (GC) activator), ANP (membrane-linked GC activator), and 8-Br-cGMP (cGMP analogue) caused a concentration-dependent vasodilation that was markedly augmented by endothelium removal. However, vasodilation induced by YC-1 and BAY41-2272 (selective soluble GC activator) was not augmented by endothelium removal. When methylene blue (soluble GC inhibitor) was present in the medium, SNP caused a concentration-dependent vasodilation in the preparation with intact endothelium, which was less augmented by endothelium removal compared with control (preparation without methylene blue). These findings suggest that endothelium removal affects intracellular cGMP-mediated signal transduction system in vascular smooth muscle cells.

Original languageEnglish
Pages (from-to)729-733
Number of pages5
JournalYakugaku Zasshi
Volume127
Issue number4
DOIs
Publication statusPublished - Apr 1 2007
Externally publishedYes

Keywords

  • Cyclic GMP
  • Endothelium-derived relaxing factor (EDRF)
  • Vasodilation

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science

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