Nitric oxide donors enhance calcitonin gene-related peptide-induced elevations of cyclic AMP in vascular smooth muscle cells.
Vasorelaxant effects of calcitonin gene-related peptide (CGRP) are dependent on endothelium-derived nitric oxide (NO) in some arteries. The mechanism involved is still not clear. In the present study, we used NO donors (sodium nitroprusside (SNP) and 6-(2-hydroxy-1-methyl-2-nitrisohydrazino)-N-methyl-1-hyxanamine (NOC-9)), cyclic GMP elevator (brain natriuretic peptide (BNP)) and a selective type III (cyclic GMP-inhibited) phosphodiesterase (PDE) inhibitor 5-(4-acetamidophenyl)pyrazin-2(1H)-one (SK&F94120) to investigate involvement of NO, cyclic GMP and type III PDE in CGRP-induced accumulation of cyclic AMP in cultured rat aortic smooth muscle cells. SNP (10 microM), NOC-9 (10 microM) and BNP (1 microM) all increased intracellular cyclic GMP to similar levels (2- to 2.5-fold above basal) and caused significant enhancement of CGRP (10 nM)-induced cyclic AMP accumulation similar to that caused by 10 microM SK&F 94120. The data are therefore consistent with our hypothesis that the mechanism of endothelium-dependent vasorelaxation effect of CGRP involves cyclic GMP-mediated inhibition of type III PDE and subsequent accumulation of cyclic AMP in smooth muscle cells.
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Department of Physiology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories.
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D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology*; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism*; D006152:Cyclic GMP / Q000378:metabolism*; D004347:Drug Interactions; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D020097:Natriuretic Peptide, Brain; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D051381:Rats; D014226:Triazenes / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology*
D020030:Nitric Oxide Donors; D010726:Phosphodiesterase Inhibitors; D014226:Triazenes; D014665:Vasodilator Agents; D020097:Natriuretic Peptide, Brain; C099612:NOC 9; D009599:Nitroprusside; D000242:Cyclic AMP; D006152:Cyclic GMP; D015740:Calcitonin Gene-Related Peptide