老年大鼠血管α1肾上腺素受体及其亚型的改变

本工作用离体与整体实验方法,研究了老年(18月龄)与年轻(3月龄)大鼠血管中 α_1肾上腺素受体储备和 α_1(?)与 α_(1b)亚型比值的差别。在离体实验中用机械方法分离血管,用 Krebs 溶液灌流,在灌流液中加入 α_2和 β肾上腺素受体拮抗剂,然后用去甲肾上腺素(NE)激动 α_1受体。结果显示;老年大鼠主动脉、肾动脉和肠系膜动脉由去甲肾上腺素(NE)引起的最大收缩反应与年轻大鼠无显著差别,但浓度-效应曲线显著右移,功能性解离常数 K_A 值不变,而 K_A 与EC_(50)的比值减小。此外,在老年大鼠主动脉和肠系膜动脉血管,选择性 α_(1b)亚型拮抗剂 CEC对 NE 引起的缩血管效应的阻断作用显著减弱,硝苯吡啶(选择性阻断 α_(1a) 亚型的效应)对 NE 缩血管效应的阻断作用显著增强。整体实验显示老年大鼠硝苯吡啶的降血压作用比年轻大鼠增强,在用硝苯吡啶的基础上给予苯肾上腺素升血压作用减弱。上述结果提示:与年轻大鼠相比较,老年大鼠 α_(1-) 肾上腺素受体储备减少,α_(1a) 亚型相对 α_(1b)亚型的比率增高。

CHANGES OF a_1-ADRENOCEPTOR AND ITS SUBTYPES IN BLOOD VESSELS OF OLD RATS

Differences in the vascular alpha 1-adrenoceptor reserve and alpha 1a to alpha 1b subtype ratio between old (18 months) and young (3 months) rats were investigated by both in vitro and in vivo experiments. For the in vitro experiments, ring preparations of blood vessels with endothelium removed were prepared and were perfused with Kreb's solution. Antagonists for alpha 2- and beta-adrenoceptors were put in perfusate in order that norepinephrine (NE) could only activate alpha 1-receptor. The results showed that, in comparison with young rats, the maximal contractions induced by NE in aorta, renal arteries and mesenteric arteries isolated from old rats were not changed but the concentration-response curves were shifted to the right. Functional dissociation constant KA for NE was not changed but the ratio of KA to EC50 was decreased. In the aortae and mesenteric arteries from old rats, the blocking effect of chlorethylclonidine (CEC, selective alpha 1b-subtype antagonist) on NE-induced contraction was decreased significantly, while the effect of nifedipine (selectively blocks the response of alpha 1a-subtype) was increased. The in vivo experiments showed that the effect of nifedipine in lowering blood pressure was stronger in the old rats than in the young rats, while following administration of nifedipine, the effect of phenylephrine in raising blood pressure was weaker. These results indicate that, in comparison with the young rats, the alpha 1-adrenoceptor reserve is decreased and the ratio of alpha 1a-subtype to alpha 1b subtype is increased in blood vessels of old rats.