Abstract
The aim of this study was to determine the hemodynamic responses elicited by systemic injections of (i) the nitric oxide (NO)-donors, sodium nitroprusside (10 nmol/kg, i.v.) and ( Z)-1-| N-methyl- N-[6( N-methylammoniohexyl)amino]|diazen-1-ium-1,2-diolate (MAHMA NONOate, 25 nmol/kg, i.v.), (ii) the endothelium-derived S-nitrosothiol, l- S-nitrosocysteine (100 nmol/kg, i.v.), and (iii) the endothelium-dependent agonist, acetylcholine (1.0 μg/kg, i.v.), in anesthetized rats, before and after injection of the voltage-sensitive Ca 2+-channel (Ca VS 2+-channel) blocker, nifedipine (500 nmol/kg, i.v.). Before injection of nifedipine, the agents produced similar falls in mean arterial blood pressure, and in hindquarter and mesenteric vascular resistances. The depressor and vasodilator responses elicited by sodium nitroprusside and MAHMA NONOate were markedly attenuated by nifedipine. The falls in mean arterial blood pressure and mesenteric resistance elicited by l- S-nitrosocysteine and acetylcholine were not attenuated but the falls in hindquarter resistance were slightly attenuated by nifedipine. The cyclooxygenase inhibitor, indomethacin (10 mg/kg, i.v.), did not affect the actions of sodium nitroprusside, MAHMA NONOate, l- S-nitrosocysteine or acetylcholine or the effects of nifedipine on the hemodynamic actions of these compounds. The decomposition of sodium nitroprusside (0.2 nmol/ml), MAHMA NONOate (0.5 nmol/ml) and l- S-nitrosocysteine (2 nmol/ml) to NO upon addition to rat blood was not affected by nifedipine (10 μM). These findings suggest that (i) exogenously applied NO relaxes resistance arteries in vivo by inhibition of Ca VS 2+-channels whereas l- S-nitrosocysteine and the non-prostanoid endothelium-derived relaxing factor (EDRF) released by acetylcholine acts by additional mechanisms, and (ii) this EDRF may be an S-nitrosothiol which acts independently of its decomposition to NO.
Published Version
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