A novel capsaicin derivative VOA induced relaxation in rat mesenteric and aortic arteries: Involvement of CGRP, NO, cGMP, and endothelium-dependent activities

Yi Ching Lo, Hui Chuan Hsiao, Deng Chyang Wu, Rong Jyh Lin, Jhy Chong Liang, Jwu Lai Yeh, Ing Jun Chen*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)

Abstract

The vasorelaxant effects of N-{4-O-[2-methoxy, phenoxyethylaminobutyl]-3-methoxy benzyl}-nonamide (VOA), a novel capsaicin derivative, and associated releasing activities of nitric oxide (NO) and calcitonin gene-related peptide (CGRP) were investigated in this study. Systemic administration of VOA decreased blood pressure and heart rate in a dose-dependent manner in both normotensive as well as spontaneously hypertensive rats. NW-nitro-L-arginine methyl ester (L-NAME), glibenclamide, and capsazepine inhibited VOA-induced hypotension. In phenylephrine-precontracted rat aortic rings and mesenteric arteries with intact endothelium, VOA caused a concentration-dependent relaxation. This relaxation was reduced after endothelium was removed or pretreated with L-NAME, methylene blue, 1 H-[1,2,4]oxidazolol [4,3-a] quinoxalin-1-one, tetraethylammonium, glibenclamide, CGRP (8-37), or capsazepine, respectively. In endothelially denuded vessel rings, tetraethylammonium, glibenclamide, CGRP (8-37), and capsazepine also reduced VOA-induced relaxation. In high potassium (80 mmol/L)-precontracted rat aortic rings with intact endothelium, VOA failed to induce relaxation. VOA induced a concentration-dependent increase of CGRP-like enzyme immunoreactivity, which was also significantly inhibited by capsazepine. In human umbilical vein endothelial cells, VOA increased NO release and guanosine-3′, 5′-cyclic monophosphate level, which were significantly inhibited by L-NAME. The Western blot analysis on human umbilical vein endothelial cells indicated that VOA increased the expression of endothelium nitric oxide synthase. In conclusion, VOA might exert its relaxation effects in rat vascular smooth muscle through the CGRP/K ATP channel and the NO/cGMP pathway.

Original languageEnglish
Pages (from-to)511-520
Number of pages10
JournalJournal of Cardiovascular Pharmacology
Volume42
Issue number4
DOIs
Publication statusPublished - 2003 Oct 1
Externally publishedYes

Keywords

  • CGRP
  • Cyclic GMP
  • K channel
  • Nitric oxide
  • VOA

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

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