Kauser K, Rubanyi G M
Berlex Biosciences, Cardiovascular Department, Richmond, Calif 94804-0099, USA.
Hypertension. 1995 Apr;25(4 Pt 1):517-23. doi: 10.1161/01.hyp.25.4.517.
We investigated endothelium-dependent responses of thoracic aorta isolated from age-matched male and female spontaneously hypertensive rats (SHR) to explore gender differences in endothelial dysfunction that may contribute to the sexual dimorphism observed in the development of hypertension in this strain. Endothelium-dependent relaxation in response to acetylcholine (10(-9) to 10(-4) mol/L) was significantly greater in female rats than in male rats, although impaired responses were seen in both sexes compared with normotensive controls. Inhibition of cyclooxygenase by indomethacin (10(-5) mol/L) improved endothelium-dependent relaxation, but it did not abolish the gender difference. Relaxations in response to sodium nitroprusside were identical in denuded aortic rings from male and female SHR. Acetylcholine at higher concentrations (10(-6) to 10(-4) mol/L) induced endothelium-dependent contraction in intact, quiescent aortic rings from male SHR but not in those from female SHR. After incubation with NG-nitro-L-arginine (10(-4) mol/L), contraction in response to acetylcholine became apparent in rings from female SHR, but it was still significantly less pronounced than in similarly treated rings from male SHR. Endothelium-dependent contraction was prevented by indomethacin in both sexes, suggesting that a cyclooxygenase product such as endoperoxide may be mediating this effect. Because responses evoked by the thromboxane/endoperoxide receptor agonist U46619 (10(-10) to 10(-6) mol/L) were not greater in rings from male SHR than those from female SHR, increased smooth muscle responsiveness or higher thromboxane/endoperoxide receptor density in the males could not account for the differences in endothelium-dependent contraction. These results suggest that sex steroid hormones may control endothelium-dependent vascular reactivity.(ABSTRACT TRUNCATED AT 250 WORDS)
我们研究了从年龄匹配的雄性和雌性自发性高血压大鼠（SHR）分离出的胸主动脉的内皮依赖性反应，以探讨内皮功能障碍中的性别差异，这种差异可能导致该品系高血压发展过程中出现的性别二态性。尽管与正常血压对照组相比，两性的反应均受损，但雌性大鼠对乙酰胆碱（10⁻⁹至10⁻⁴mol/L）的内皮依赖性舒张明显大于雄性大鼠。吲哚美辛（10⁻⁵mol/L）抑制环氧化酶可改善内皮依赖性舒张，但并未消除性别差异。雄性和雌性SHR去内皮主动脉环对硝普钠的舒张反应相同。较高浓度（10⁻⁶至10⁻⁴mol/L）的乙酰胆碱可诱导雄性SHR完整、静息主动脉环产生内皮依赖性收缩，但雌性SHR的主动脉环则不会。用NG-硝基-L-精氨酸（10⁻⁴mol/L）孵育后，雌性SHR主动脉环对乙酰胆碱的收缩反应变得明显，但仍明显弱于同样处理的雄性SHR主动脉环。吲哚美辛可在两性中阻止内皮依赖性收缩，这表明环氧化酶产物如内过氧化物可能介导了这种效应。由于血栓素/内过氧化物受体激动剂U46619（10⁻¹⁰至10⁻⁶mol/L）在雄性SHR主动脉环中引起的反应并不大于雌性SHR主动脉环，因此雄性平滑肌反应性增加或血栓素/内过氧化物受体密度较高并不能解释内皮依赖性收缩的差异。这些结果表明，性类固醇激素可能控制内皮依赖性血管反应性。（摘要截断于250字）
