Effects of Some Inorganic Divalent Cations and Protein Kinase C Inhibitors on Endothelium-Dependent Relaxation in Rat Isolated Aorta and Mesenteric Arteries
The effects of nitrendipine and several metal ions possessing Ca 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 a...
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Veröffentlicht in: | Journal of cardiovascular pharmacology 1991-10, Vol.18 (4), p.511-521 |
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Sprache: | eng |
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Zusammenfassung: | The effects of nitrendipine and several metal ions possessing Ca 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 Co, Mn, and Ni, but not the nontransition ions (Cd, Sn and Zn, 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 Mn but not by Co or Ni. 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 Ca 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 Ca channel; and (c) that the inhibitory effects of the calmodulin antagonists may reflect an action on endothelial NO synthase. |
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ISSN: | 0160-2446 1533-4023 |
DOI: | 10.1097/00005344-199110000-00006 |