Coronary vascular reactivity is improved by endothelin A receptor blockade in DOCA-salt hypertensive rats.
Coronary vascular reactivity is improved by endothelin A receptor blockade in DOCA-salt hypertensive rats.
复制标题
DOCA-盐高血压大鼠的内皮素 A 受体阻断可改善冠状血管反应性。
DOI：
10.1152/ajpregu.1998.274.6.r1613
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发表时间：
1998
期刊：
影响因子：
--
通讯作者：
Fuchs,LC
中科院分区：
文献类型：
--
作者：
Giulumian,AD;Pollock,DM;Clarke,N;Fuchs,LC
Endothelin-1 (ET-1) is thought to play an important role in the development of deoxycorticosterone acetate (DOCA)-salt hypertension. Because hypertension is associated with an increased incidence of coronary artery disease, this study was designed to determine if coronary vascular contraction to ET-1 is altered in DOCA-salt hypertensive rats and to determine the effect of chronic treatment of DOCA-salt rats with the selective ETAreceptor antagonist A-127722. Male Sprague-Dawley rats were divided into four groups: DOCA, Placebo, DOCA + A-127722, and Placebo + A-127722. A-127722 was administered in drinking water at a concentration of 8 mg/100 ml. After 3 wk, mean arterial pressure (MAP) was significantly enhanced in DOCA-salt compared with Placebo rats. A-127722 significantly inhibited the increase in MAP. Contraction to ET-1 (10−11to 3 × 10−8M) was measured in isolated coronary and mesenteric small arteries (200–300 μm, intraluminal diameter) maintained at a constant intraluminal pressure of 40 mmHg and was significantly impaired in vessels from DOCA-salt compared with Placebo rats. Dose-dependent contractions to KCl were also inhibited in coronary, but only minimally impaired in mesenteric, arteries of DOCA-salt rats. Inhibition of nitric oxide synthase activity did not restore contraction to ET-1 in coronary small arteries. However contractions to ET-1 were enhanced in mesenteric small arteries. Chronic treatment with A-127722 significantly restored contraction to ET-1 in coronary, but not in mesenteric, arteries of DOCA-salt rats. Because ETAreceptor blockade impairs the development of hypertension and improves coronary vascular reactivity, these data indicate that ET-1 plays an important role in coronary vascular dysfunction associated with DOCA-salt hypertension.
