Perry P A, Webb R C
School of Nursing, University of Michigan, Ann Arbor 48109.
Can J Physiol Pharmacol. 1988 Aug;66(8):1095-9. doi: 10.1139/y88-179.
This study examines vascular reactivity to alpha-adrenoceptor agonists in mineralocorticoid (deoxycorticosterone acetate (DOCA-salt) hypertensive and normotensive rats. The rats were anesthetized and the mesenteric artery was excised and cut helically into strips that were mounted in a muscle bath for the measurement of isometric force development. Addition of norepinephrine, epinephrine, phenylephrine, methoxamine, or clonidine to the bath caused contractions in all arteries. Arteries from hypertensive rats were more sensitive (lower ED50 values) to each of the agonists than arteries from normotensive rats. alpha-Adrenoceptor affinity for phentolamine (Schild analysis; norepinephrine as the agonist) in hypertensive arteries was not significantly different from that in normotensive arteries. Maximal force generation to clonidine was greater in hypertensive arteries than in normotensive arteries. These results demonstrate an augmented vascular sensitivity to several alpha-adrenoceptor agonists in DOCA hypertensive rats. This change in sensitivity is independent of a change in affinity for the adrenoceptor antagonist, phentolamine. It may be that a change in receptor number or an alteration in a post-receptor activation event accounts for this enhanced adrenoceptor responsiveness in mineralocorticoid hypertension.
本研究检测了盐皮质激素（醋酸脱氧皮质酮（DOCA-盐））高血压大鼠和正常血压大鼠血管对α-肾上腺素能受体激动剂的反应性。将大鼠麻醉后，切除肠系膜动脉并螺旋形切成条带，安装在肌肉浴槽中以测量等长力的产生。向浴槽中加入去甲肾上腺素、肾上腺素、去氧肾上腺素、甲氧明或可乐定均会引起所有动脉收缩。高血压大鼠的动脉对每种激动剂的敏感性均高于正常血压大鼠（半数有效剂量（ED50）值更低）。高血压动脉对酚妥拉明的α-肾上腺素能受体亲和力（希尔德分析；以去甲肾上腺素作为激动剂）与正常血压动脉相比无显著差异。高血压动脉对可乐定产生的最大力量大于正常血压动脉。这些结果表明，DOCA高血压大鼠血管对几种α-肾上腺素能受体激动剂的敏感性增强。这种敏感性变化与对肾上腺素能受体拮抗剂酚妥拉明的亲和力变化无关。可能是受体数量的改变或受体后激活事件的改变导致了盐皮质激素性高血压中这种增强的肾上腺素能受体反应性。
