Abstract
The effects of a nitric oxide-donor, S-nitroso- N-acetylpenicillamine, and a direct activator of soluble guanylyl cyclase, 3-(5′-hydroxymethyl-2′-furyl)-1-benzyl indazole (YC-1), on force of contraction ( F c) and L-type Ca 2+ currents ( I Ca(L)) were investigated in myocardial preparations from neonatal and adult rats. Since hearts from adult and neonatal animals contained 160 and 47 mg/100 g wet weight myoglobin, respectively, its possible interaction with both drugs was also investigated. Both S-nitroso- N-acetylpenicillamine (100 μM) and YC-1 (30 μM) were ineffective in myocardial preparations from adult rats but reduced the magnitude of I Ca(L) and F c in preparations from neonatal rats. The latter effects were antagonised by 1 H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; 50 μM) and attenuated by myoglobin (30–300 μM), which also attenuated the effects of both drugs on pre-contracted aortic rings. The differential effects of S-nitroso- N-acetylpenicillamine and YC-1 in the myocardium from adult and neonatal rats may result from developmental changes in the content of myoglobin and/or in the NO/soluble guanylyl cyclase signal pathway.
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