The vasodilator potency of the endothelium-derived relaxing factor, l-S-nitrosocysteine, is impaired in conscious spontaneously hypertensive rats

ObjectiveThis study compared the hemodynamic responses elicited by the endothelium-derived relaxing factor (EDRF), l-S-nitrosocysteine (l-SNC), the non-prostanoid EDRF released by acetylcholine (ACh) and nitric oxide (NO)-donors such as MAHMA NONOate, in conscious spontaneously hypertensive (SH) and normotensive Wistar–Kyoto (WKY) rats.MethodsThe depressor and/or vasodilator responses elicited by intravenous injections of ACh, l-SNC and MAHMA NONOate were determined in adult WKY and SH rats before and after intravenous injection of the NO synthesis inhibitor, NG-nitro-l-arginine methylester (l-NAME), or the cyclooxygenase inhibitor, indomethacin.ResultsThe responses elicited by ACh and l-SNC were smaller in SH than in WKY rats whereas the responses elicited by MAHMA NONOate were augmented in SH rats. The ACh-induced responses were not diminished after injection of l-NAME in WKY or SH rats. Indomethacin did not affect the responses to any of the vasodilator agents in WKY or SH rats. Addition of l-SNC to whole blood or thoracic aortae from SH rats yielded similar amounts of NO to those of WKY rats.ConclusionsThe vasodilator potencies of ACh and l-SNC were diminished whereas that of NO was augmented in SH rats. The loss of potency of l-SNC in SH rats was not obviously due to differences in decomposition to NO or the overactivity of cyclooxygenase factors. This study provides the first evidence that diminished endothelium-dependent vasodilation in SH rats may involve a loss of vasodilator potency of endogenous l-SNC.