Lüscher T F, Vanhoutte P M
Hypertension. 1986 Apr;8(4):344-8. doi: 10.1161/01.hyp.8.4.344.
To study the mechanism of decreased endothelium-dependent relaxations in spontaneously hypertensive rats (SHR), rings of thoracic aorta with and without endothelium were taken from age-matched male SHR and normotensive Wistar-Kyoto rats (WKY) and suspended for isometric tension recording. Acetylcholine caused endothelium-dependent contractions in quiescent rings from SHR but not in those from WKY. These contractions were inhibited by atropine but not by hexamethonium and were prevented by inhibitors of phospholipase A2 or cyclooxygenase but not by inhibitors of prostacyclin synthetase, thromboxane synthetase, or leukotriene synthetase. Prostaglandin D2, E1, E2, and F2 alpha caused concentration-dependent contractions in rings without endothelium from both SHR and WKY; the responses to the highest concentration (10(-5) M) of the individual prostaglandins were comparable in both strains. Endothelium-dependent relaxations evoked by high but not by low concentrations of acetylcholine were significantly depressed in SHR as compared with those in WKY (p less than 0.05). Indomethacin normalized endothelium-dependent relaxations in SHR. Thus, acetylcholine can activate muscarinic receptors that evoke endothelium-dependent contractions in the aorta of SHR but not in that of WKY. The contraction probably is mediated by a cyclooxygenase product(s) other than prostacyclin or thromboxane A2. The reduced endothelium-dependent relaxations to acetylcholine in the SHR probably are not due to a decreased release of endothelium-derived relaxing factor(s) but to the simultaneous release of endothelium-derived contracting substance(s).
为研究自发性高血压大鼠（SHR）内皮依赖性舒张功能降低的机制，从年龄匹配的雄性SHR和血压正常的Wistar-Kyoto大鼠（WKY）获取有或无内皮的胸主动脉环，悬挂起来进行等长张力记录。乙酰胆碱可使SHR的静态血管环产生内皮依赖性收缩，但WKY的血管环则不会。这些收缩可被阿托品抑制，但不能被六甲铵抑制，且可被磷脂酶A2或环氧化酶抑制剂阻断，但不能被前列环素合成酶、血栓素合成酶或白三烯合成酶抑制剂阻断。前列腺素D2、E1、E2和F2α可使SHR和WKY无内皮的血管环产生浓度依赖性收缩；两种品系对单个前列腺素最高浓度（10⁻⁵ M）的反应相当。与WKY相比，SHR中高浓度而非低浓度乙酰胆碱诱发的内皮依赖性舒张明显减弱（p<0.05）。吲哚美辛可使SHR的内皮依赖性舒张恢复正常。因此，乙酰胆碱可激活毒蕈碱受体，从而在SHR的主动脉而非WKY的主动脉中诱发内皮依赖性收缩。这种收缩可能由除前列环素或血栓素A2之外的环氧化酶产物介导。SHR中对乙酰胆碱内皮依赖性舒张的降低可能不是由于内皮源性舒张因子释放减少，而是由于内皮源性收缩物质的同时释放。
