Arribas S, Marín J, Ponte A, Balfagón G, Salaices M
Departamento de Farmacología y Terapéutica, Facultad de Medicina, Universidad Autónoma, Madrid, Spain.
J Pharmacol Exp Ther. 1994 Aug;270(2):520-7.
The objective of the present work has been to analyze the influence of endothelium, ageing and hypertension in the norepinephrine (NE)-induced responses. For this purpose we used aortic rings from spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats of different ages. In rings with endothelium from 5-week-old WKY, cumulative addition of NE (0.01 and 0.1 microM) caused concentration-dependent contractions, whereas higher concentrations (1 and 10 microM) induced concentration-dependent relaxations. In 5-week-old SHR and 3-month-old WKY rats, these relaxant responses were observed only at 10 microM NE, and they disappeared in older animals from both strains. In endothelium denuded rings, NE induced only contractions, which were similar in WKY rats of different ages, but significantly increased in 6- and 12-month-old SHR. In both strains, the endothelium-dependent relaxant responses to NE were abolished by NG-nitro-L-arginine methyl ester and propranolol, but not modified by yohimbine or ouabain. Isoproterenol (0.01-10 microM) induced concentration-dependent vasodilation in rings from 5-week-old rats of both strains, precontracted with 1 microM NE. Isoproterenol-elicited responses were reduced by endothelium removal or by 0.1 mM NG-nitro-L-arginine methyl ester and abolished by 1 microM propranolol. These results suggest that: 1) in the aorta from young WKY and prehypertensive SHR rats, NE induces vasodilations mediated by activation of endothelial beta adrenoceptors and release of nitric oxide; 2) these responses are impaired during ageing and hypertension; and 3) there is an important negative endothelial modulation of NE-induced contraction in adult SHR rats.
本研究的目的是分析内皮、衰老和高血压对去甲肾上腺素（NE）诱导反应的影响。为此，我们使用了不同年龄的自发性高血压（SHR）大鼠和Wistar-Kyoto（WKY）大鼠的主动脉环。在5周龄WKY大鼠带内皮的主动脉环中，累积添加NE（0.01和0.1微摩尔）会引起浓度依赖性收缩，而更高浓度（1和10微摩尔）则诱导浓度依赖性舒张。在5周龄的SHR大鼠和3月龄的WKY大鼠中，这些舒张反应仅在10微摩尔NE时观察到，并且在两个品系的老年动物中消失。在内皮剥脱的主动脉环中，NE仅诱导收缩，不同年龄的WKY大鼠的收缩情况相似，但在6月龄和12月龄的SHR大鼠中显著增加。在两个品系中，NE诱导的内皮依赖性舒张反应被NG-硝基-L-精氨酸甲酯和普萘洛尔消除，但不受育亨宾或哇巴因影响。异丙肾上腺素（0.01 - 10微摩尔）在两个品系5周龄大鼠预先用1微摩尔NE预收缩的主动脉环中诱导浓度依赖性血管舒张。异丙肾上腺素引发的反应因内皮去除或0.1毫摩尔NG-硝基-L-精氨酸甲酯而降低，并被1微摩尔普萘洛尔消除。这些结果表明：1）在年轻的WKY大鼠和高血压前期SHR大鼠的主动脉中，NE通过激活内皮β肾上腺素能受体和释放一氧化氮介导血管舒张；2）这些反应在衰老和高血压过程中受损；3）在成年SHR大鼠中，内皮对NE诱导的收缩有重要的负性调节作用。
