Guerrero Estela, Voces Felipe, Ardanaz Noelia, Montero María José, Arévalo Miguel, Sevilla María Angeles
Departamento de Farmacología, Facultad de Medicina, Universidad de Panamá, Spain.
J Cardiovasc Pharmacol. 2003 Sep;42(3):348-55. doi: 10.1097/00005344-200309000-00005.
The aim of this study was to assess the effects of long-term nebivolol therapy on high blood pressure, impaired endothelial function in aorta, and damage observed in heart and conductance arteries in spontaneously hypertensive rats (SHR). For this purpose, SHR were treated for 9 weeks with nebivolol (8 mg/kg per day). Untreated SHR and Wistar Kyoto rats were used as hypertensive and normotensive controls, respectively. The left ventricle/body weight ratio was used as an index of cardiac hypertrophy, and to evaluate vascular function, responses induced by potassium chloride, noradrenaline, acetylcholine, and sodium nitroprusside were tested on aortic rings. Aortic morphometry and fibrosis were determined in parallel by a quantitative technique. Systolic blood pressure, measured by the tail-cuff method, was lower in treated SHR than in the untreated group (194 +/- 3 versus 150 +/- 4 mm Hg). The cardiac hypertrophy index was significantly reduced by the treatment. In aortic rings, treatment with nebivolol significantly reduced the maximal response to both KCl and NA in SHR. In vessels precontracted with phenylephrine relaxant, activity due to acetylcholine was higher in normotensive rats than in SHR and the treatment significantly improved this response. The effect of sodium nitroprusside on aortic rings was similar in all groups. Medial thickness and collagen content were significantly reduced in comparison with SHR. In conclusion, the chronic antihypertensive effect of nebivolol in SHR was accompanied by an improvement in vascular structure and function and in the cardiac hypertrophy index.
本研究的目的是评估长期使用奈必洛尔治疗对自发性高血压大鼠（SHR）的高血压、主动脉内皮功能受损以及心脏和传导动脉损伤的影响。为此，对SHR用奈必洛尔（每天8毫克/千克）治疗9周。未治疗的SHR和Wistar Kyoto大鼠分别用作高血压和正常血压对照。左心室/体重比用作心脏肥大的指标，为评估血管功能，在主动脉环上测试氯化钾、去甲肾上腺素、乙酰胆碱和硝普钠诱导的反应。通过定量技术并行测定主动脉形态学和纤维化。用尾套法测量的收缩压，治疗的SHR低于未治疗组（194±3对150±4毫米汞柱）。治疗可显著降低心脏肥大指数。在主动脉环中，奈必洛尔治疗显著降低了SHR对KCl和NA的最大反应。在预先用去氧肾上腺素收缩的血管中，乙酰胆碱引起的活性在正常血压大鼠中高于SHR，且治疗显著改善了这种反应。硝普钠对主动脉环的作用在所有组中相似。与SHR相比，中膜厚度和胶原含量显著降低。总之，奈必洛尔对SHR的慢性降压作用伴随着血管结构和功能以及心脏肥大指数的改善。
