Fuchs L C, Nuno D, Lamping K G, Johnson A K
Department of Pharmacology, University of Iowa, Iowa City 52242, USA.
Am J Hypertens. 1996 May;9(5):475-83. doi: 10.1016/0895-7061(95)00441-6.
Coronary artery disease often occurs in patients with hypertension. The present study was designed to evaluate coronary vascular function in isolated coronary arteries of spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats and to determine the effect of antihypertensive treatment on coronary vascular responsiveness. Male SHR and WKY rats (12 to 14 weeks old) were divided into control and hydralazine-treated (120 mg/L drinking water for 10 days) groups. After 10 days, arterial pressure and heart rate were recorded while rats were conscious and unrestrained. Left ventricular coronary arteries (200 to 300 microns diameter) were isolated and intraluminal diameter was continuously recorded while vessels were maintained at a constant intraluminal pressure of 40 mm Hg. Relaxation of coronary arteries to both acetylcholine and nitroprusside was slightly, but significantly, enhanced in vessels from SHR compared to WKY rats. The enhanced relaxation was a specific effect, since isoproterenol induced similar relaxation in coronary arteries from SHR and WKY rats. Contraction to phenylephrine, but not endothelin-1, was augmented in coronary arteries from SHR compared to WKY rats. Treatment with hydralazine significantly lowered arterial pressure in SHR and WKY rats, but did not alter the enhanced contraction to phenylephrine or the enhanced relaxation to acetylcholine and nitroprusside in coronary arteris from SHR. These results indicate that coronary arteries of 12 to 14 week-old SHR do not have impaired endothelium-dependent relaxation, but to exhibit enhanced alpha-adrenoceptor-mediated contraction that is not reduced by lowering arterial pressure.
冠状动脉疾病常发生于高血压患者。本研究旨在评估自发性高血压大鼠（SHR）和Wistar-Kyoto（WKY）大鼠离体冠状动脉的血管功能，并确定降压治疗对冠状动脉反应性的影响。将雄性SHR和WKY大鼠（12至14周龄）分为对照组和肼屈嗪治疗组（饮用含120 mg/L肼屈嗪的水10天）。10天后，在大鼠清醒且不受约束的状态下记录动脉血压和心率。分离出左心室冠状动脉（直径200至300微米），并在血管腔内压力维持在40 mmHg恒定水平时连续记录管腔内直径。与WKY大鼠相比，SHR大鼠冠状动脉对乙酰胆碱和硝普钠的舒张作用略有增强，但具有显著性差异。这种增强的舒张作用是一种特异性效应，因为异丙肾上腺素在SHR和WKY大鼠冠状动脉中诱导的舒张作用相似。与WKY大鼠相比，SHR大鼠冠状动脉对去氧肾上腺素的收缩反应增强，但对内皮素-1的收缩反应无增强。用肼屈嗪治疗可显著降低SHR和WKY大鼠的动脉血压，但并未改变SHR大鼠冠状动脉对去氧肾上腺素增强的收缩反应或对乙酰胆碱和硝普钠增强的舒张反应。这些结果表明，12至14周龄SHR大鼠的冠状动脉内皮依赖性舒张功能并未受损，但表现出增强的α-肾上腺素能受体介导的收缩反应，且这种反应不会因降低动脉血压而减弱。
