Lewis Stephen J, Hashmi-Hill Maleka P, Owen Joy R, Sandock Kevin, Robertson Tom P, Bates James N
Department of Physiology and Pharmacology, Institute of Comparative Medicine, College of Veterinary Medicine, University of Georgia, Athens, GA 30602-7389, USA.
Vascul Pharmacol. 2006 Jun;44(6):476-90. doi: 10.1016/j.vph.2006.03.013. Epub 2006 May 11.
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.
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.
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.
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.
本研究比较了内皮源性舒张因子（EDRF）、L-半胱氨酸亚硝基硫醇（L-SNC）、乙酰胆碱（ACh）释放的非前列腺素类EDRF以及一氧化氮（NO）供体如MAHMA NONOate在清醒的自发性高血压（SH）大鼠和正常血压的Wistar-Kyoto（WKY）大鼠中引起的血流动力学反应。
在成年WKY和SH大鼠静脉注射NO合成抑制剂N（G）-硝基-L-精氨酸甲酯（L-NAME）或环氧合酶抑制剂吲哚美辛之前和之后，测定静脉注射ACh、L-SNC和MAHMA NONOate引起的降压和/或血管舒张反应。
SH大鼠中ACh和L-SNC引起的反应比WKY大鼠小，而MAHMA NONOate引起的反应在SH大鼠中增强。在WKY或SH大鼠中注射L-NAME后，ACh诱导的反应没有减弱。吲哚美辛对WKY或SH大鼠中任何血管舒张剂的反应均无影响。向SH大鼠的全血或胸主动脉中添加L-SNC产生的NO量与WKY大鼠相似。
SH大鼠中ACh和L-SNC的血管舒张能力减弱，而NO的血管舒张能力增强。SH大鼠中L-SNC效力的丧失显然不是由于分解为NO的差异或环氧合酶因子的过度活性。本研究提供了首个证据，表明SH大鼠中内皮依赖性血管舒张减弱可能涉及内源性L-SNC血管舒张效力的丧失。
