Clinical guidelines suggest the combination of 2 drugs as a strategy to treat hypertension. However, some antihypertensive combinations have been shown to be ineffective. Therefore, it is necessary to determine whether differences exist between the results of monotherapy and combination therapy by temporal monitoring of the responses to angiotensin II and norepinephrine, which are vasoconstrictors involved in the development of hypertension. Thus, the purpose of this work was to determine the vascular reactivity to angiotensin II and norepinephrine in spontaneously hypertensive rat (SHR) aortic rings after treatment with valsartan, lisinopril, nebivolol, nebivolol-lisinopril, and nebivolol-valsartan for different periods of time. In this study, male SHR and Wistar Kyoto normotensive (WKY) rats were divided into 7 groups treated for 1, 2, and 4 weeks: (1) WKY + vehicle, (2) SHR + vehicle; (3) SHR + nebivolol; (4) SHR + lisinopril; (5) SHR + valsartan; (6) SHR + nebivolol-lisinopril; and (7) SHR + nebivolol-valsartan. Blood pressure was measured by the tail-cuff method, and vascular reactivity was determined from the concentration-response curve to angiotensin II and norepinephrine in aortic rings. The results showed that the combined and individual treatments reduced mean blood pressure at all times evaluated. All treatments decreased vascular reactivity to angiotensin II; however, in the case of lisinopril and nebivolol-lisinopril, the effect observed was significant up to 2 weeks. All treatments decreased the reactivity to norepinephrine up to week 4. These results show a time-dependent difference in vascular reactivity between the pharmacological treatments, with nebivolol-valsartan and nebivolol-lisinopril being both effective combinations. Additionally, the results suggest crosstalk between the renin-angiotensin and sympathetic nervous systems to reduce blood pressure and to improve treatment efficacy.

临床指南建议将两种药物联合使用作为治疗高血压的策略。然而，一些抗高血压组合已被证明是无效的。因此，有必要通过时间监测对血管紧张素 II 和去甲肾上腺素的反应来确定单药治疗和联合治疗的结果之间是否存在差异，血管紧张素 II 和去甲肾上腺素是参与高血压发展的血管收缩剂。因此，这项工作的目的是确定在用缬沙坦、赖诺普利、奈必洛尔、奈必洛尔-赖诺普利和奈必洛尔-缬沙坦治疗不同时间段后，自发性高血压大鼠 (SHR) 主动脉环中血管对血管紧张素 II 和去甲肾上腺素的反应性。在本研究中，雄性 SHR 和 Wistar Kyoto 血压正常 (WKY) 大鼠分为 7 组，分别治疗 1、2、和 4 周：(1) WKY + 车辆，(2) SHR + 车辆；(3) SHR+奈必洛尔；(4) SHR+赖诺普利；(5) SHR+缬沙坦；(6) SHR + 奈必洛尔-赖诺普利；(7) SHR + 奈必洛尔-缬沙坦。用尾套法测量血压，并根据主动脉环中血管紧张素 II 和去甲肾上腺素的浓度-反应曲线确定血管反应性。结果表明，联合治疗和单独治疗在评估的所有时间都降低了平均血压。所有治疗均降低血管对血管紧张素 II 的反应性；然而，在赖诺普利和奈必洛尔-赖诺普利的情况下，观察到的效果在 2 周内是显着的。直到第 4 周，所有治疗都降低了对去甲肾上腺素的反应性。这些结果显示了药物治疗之间血管反应性的时间依赖性差异，奈比洛尔-缬沙坦和奈比洛尔-赖诺普利都是有效的组合。此外，结果表明肾素-血管紧张素和交感神经系统之间的相互作用可以降低血压并提高治疗效果。