Diederich D, Yang Z H, Bühler F R, Lüscher T F
Department of Medicine, University Hospital, Basel, Switzerland.
Am J Physiol. 1990 Feb;258(2 Pt 2):H445-51. doi: 10.1152/ajpheart.1990.258.2.H445.
Endothelial cells modulate vascular tone by releasing endothelium-derived relaxing (EDRF) and contracting factors. An imbalance of these factors in hypertension could contribute to increased peripheral vascular resistance. Mesenteric resistance arteries of Wistar-Kyoto (WKY) and stroke-prone spontaneously hypertensive rats (SHRSP) were suspended in a myograph filled with physiological salt solution (37 degrees C; 95% O2-5% CO2). In WKY rings contracted with norepinephrine, acetylcholine (10(-9)-10(-4) M) evoked endothelium-dependent relaxations (88 +/- 2%, IC50 7.3 +/- 0.1; n = 31). Hemoglobin (10(-5) M) but not meclofenamate (10(-5) M) reversed the relaxations delineating EDRF as the mediator. Nitric oxide (3 X 10(-9)-10(-5) M) induced comparable relaxations as acetylcholine. In SHRSP, relaxations to acetylcholine but not those to nitric oxide were impaired (61 +/- 5%, IC50 greater than 6.6 +/- 0.4; n = 24; P less than 0.005). In SHRSP, meclofenamate but not the thromboxane synthetase inhibitor CGS 13080 normalized endothelium-dependent relaxations. Relaxations to sodium nitroprusside were enhanced in SHRSP both in rings with and without endothelium. Thus our results are compatible with the concept that endothelium-dependent relaxations in resistance arteries are mediated by nitric oxide. In SHRSP, endothelium-dependent relaxations are impaired because of a cyclooxygenase-dependent substance interfering with the release and/or action of EDRF.
内皮细胞通过释放内皮源性舒张因子（EDRF）和收缩因子来调节血管张力。高血压状态下这些因子的失衡可能导致外周血管阻力增加。将Wistar-Kyoto（WKY）大鼠和易患中风的自发性高血压大鼠（SHRSP）的肠系膜阻力动脉悬挂于充满生理盐溶液（37℃；95% O₂ - 5% CO₂）的肌动描记器中。在去甲肾上腺素收缩的WKY动脉环中，乙酰胆碱（10⁻⁹ - 10⁻⁴ M）可引起内皮依赖性舒张（88 ± 2%，IC₅₀ 7.3 ± 0.1；n = 31）。血红蛋白（10⁻⁵ M）而非甲氯芬那酸（10⁻⁵ M）可逆转这种舒张，表明EDRF是介导因子。一氧化氮（3×10⁻⁹ - 10⁻⁵ M）引起的舒张与乙酰胆碱相当。在SHRSP中，对乙酰胆碱的舒张反应受损，但对一氧化氮的舒张反应未受损（61 ± 5%，IC₅₀大于6.6 ± 0.4；n = 24；P < 0.005）。在SHRSP中，甲氯芬那酸而非血栓素合成酶抑制剂CGS 13080可使内皮依赖性舒张恢复正常。无论有无内皮，SHRSP动脉环对硝普钠的舒张反应均增强。因此，我们的结果与阻力动脉中内皮依赖性舒张由一氧化氮介导的概念相符。在SHRSP中，内皮依赖性舒张受损是因为一种依赖环氧化酶的物质干扰了EDRF的释放和/或作用。
