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

Abstract Objective This 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. Methods The 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, N G -nitro- l -arginine methylester ( l -NAME), or the cyclooxygenase inhibitor, indomethacin. Results The 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. Conclusions The 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.