Endothelium removal augments endothelium-independent vasodilatation in rat mesenteric vascular bed

Y. Iwatani, K. Kosugi, S. Isobe-Oku, S. Atagi, Y. Kitamura, H. Kawasaki

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Background and purpose: The vascular endothelium regulates vascular tone by releasing various endothelium-derived vasoactive substances to counteract excess vascular response. We investigated whether the vascular endothelium regulates vasodilatation via released endothelium-derived contracting factors (EDCFs), by examining the effect of endothelium removal on responses to periarterial nerve stimulation (PNS) and various vasodilator agents. Experimental approach: The rat mesenteric vascular bed was perfused with Krebs solution. Vasodilator responses to PNS and 5 min perfusion of vasodilator agents in preparations with endothelium were compared with those in the same preparations without endothelium. The endothelium was removed by 30 s perfusion with sodium deoxycholate. Key results: Endothelium removal significantly augmented vasodilator responses to PNS and calcitonin gene-related peptide (CGRP), isoprenaline (β-adrenoceptor agonist), SNP and 8-bromo-cGMP (8-Br-cGMP; cGMP analogue) but not BAY41-2272 (soluble guanylate cyclase activator). The augmentation of SNP-induced vasodilatation after denudation was much greater than that of CGRP- or isoprenaline-induced vasodilatation. In the preparations with an intact endothelium, L-NAME (nitric oxide synthase inhibitor) significantly augmented vasodilator responses to PNS and CGRP, isoprenaline, SNP and 8-Br-cGMP, but not BAY41-2272. Indomethacin (cyclooxygenase inhibitor) and seratrodast (thromboxane A 2 receptor antagonist), but not phosphoramidon (endothelin-1-converting enzyme inhibitor) or BQ-123 (selective endothelin type A receptor antagonists), significantly augmented vasodilator responses to PNS and CGRP, isoprenaline, SNP and BAY41-2272. Conclusion and implication: These results suggest that the endothelium in rat mesenteric arteries regulates and maintains vascular tone via counteracting not only vasoconstriction through releasing endothelium-derived relaxing factors, but also vasodilatation, in part by releasing an EDCF, thromboxane A 2.

Original languageEnglish
Pages (from-to)32-40
Number of pages9
JournalBritish Journal of Pharmacology
Volume154
Issue number1
DOIs
Publication statusPublished - May 2008

Keywords

  • Calcitonin gene-related peptide
  • Endothelium-derived contracting factor
  • Endothelium-derived relaxing factor
  • Isoprenaline
  • Periarterial nerve stimulation
  • Sodium nitroprusside
  • Vascular endothelium removal
  • Vasodilatation

ASJC Scopus subject areas

  • Pharmacology

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