Effects of some inorganic divalent cations and protein kinase C inhibitors on endothelium-dependent relaxation in rat isolated aorta and mesenteric arteries

Ayotunde S O Adeagbo, Christopher Triggle

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Abstract

The effects of nitrendipine and several metal ions possessing Ca2+antagonistic activity were examined on acetylcholine (ACh) and histamine-induced endothelium-dependent relaxations in norepinephrine (NE)-precontracted rat aortic rings and perfused mesenteric arteries. Nitrendipine (1 nM) profoundly attenuated ACh and histamine-induced relaxations of perfused mesenteric arteries but was ineffective against either agonist in aorta. The transition metal ions Co2+, Mn2+, and Ni2+, but not the nontransition ions (Cd2+, Sn2+and Zn2+, markedly inhibited ACh and histamine relaxations in the aorta, whereas all metal ions antagonized KCI contractions. At the highest concentration devoid of effect on arterial perfusion pressure, none of the transition metal ions altered endothelium-dependent relaxations in the mesenteric arteries. Endothelium-independent relaxations induced by sodium nitroprusside (SNP) were attenuated by Mn2+but not by Co2+or Ni2+. Calmidazolium or W-7 inhibited ACh- and histamine-induced relaxations in both aorta and mesenteric arteries, whereas staurosporine and H-7 were ineffective against aortic relaxations; in mesenteric arteries. staurosporine but not H-7 attenuated both endothelium-dependent and -independent relaxations. We conclude (a) that the transition metal ions most likely inhibit endothelium-derived relaxing factor (EDRF) (NO) re-lease in the aorta through endothelial receptor-operated Ca2+channels; (c) that the effects of nitrendipine (shared by nifedipine) in mesenteric arteries result from an interaction with a site that may have structural similarities with, but is distinct from, the L-type Ca2+channel; and (c) that the inhibitory effects of the calmodulin antagonists may reflect an action on endothelial NO synthase.

Original languageEnglish
Pages (from-to)511-521
Number of pages11
JournalJournal of Cardiovascular Pharmacology
Volume18
Issue number4
Publication statusPublished - 1991
Externally publishedYes

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Keywords

  • Calmodulin
  • Endothelium-dependent relaxation
  • Inorganic Ca<sup>2+</sup>antagonists
  • Perfused mesenteric arteries
  • Rat aorta

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Pharmacology

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