Summary
The effects of the four nitro-compounds nitroglycerin, nitroprusside-Na, NaNO2 and B 744-99 were studied simultaneously on length and on cGMP-levels in isolated circular strips of bovine coronary arteries.
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1.
All 4 nitro-compounds concentration dependently relaxed the strips in close association with pronounced increases in cGMP-levels which preceded the mechanical responses.
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2.
The relaxant effects of all 4 nitro-compounds were significantly potentiated by the predominant inhibitor of cGMP-hydrolysis M & B 22,948, which also potentiated the increase in cGMP-levels of the two nitro-compounds in which it was studied (nitroglycerin and nitroprusside-Na).
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3.
Non-substituted cGMP and — much stronger —its 8 bromo-derivative also relaxed the strips and these effects were likewise potentiated by M & B 22,948.
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4.
When the log increase in cGMP produced by the 4 nitro-compounds were plotted against percent relaxation (probit scale) a linear and highly significant positive correlation was obtained.
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5.
The results provide evidence that the increases in cGMP caused by the 4 nitro-compounds studied are responsible for the smooth muscle relaxing actions of these drugs.
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Kukovetz, W.R., Holzmann, S., Wurm, A. et al. Evidence for cyclic GMP-mediated relaxant effects of nitro-compounds in coronary smooth muscle. Naunyn-Schmiedeberg's Arch. Pharmacol. 310, 129–138 (1979). https://doi.org/10.1007/BF00500277
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DOI: https://doi.org/10.1007/BF00500277