Effects of third-generation beta-blockers, atenolol or amlodipine on blood pressure variability and target organ damage in spontaneously hypertensive rats

摘要

Background: beta-blockers are no longer considered as first-line antihypertensive drugs due to their lower cardioprotection. Method: Considering the differences in the pharmacological properties of beta-blockers, the present work compared the effects of third-generation beta-blockers - carvedilol and nebivolol - with a first-line agent - amlodipine - on hemodynamic parameters, including short-term blood pressure variability (BPV), and their ability to prevent target organ damage in spontaneously hypertensive rats (SHR). SHR rats were orally treated with carvedilol, nebivolol, atenolol, amlodipine or vehicle for 8 weeks. Wistar Kyoto rats treated with vehicle were used as normotensive group. Echocardiographic evaluation, BP, and short-term BPV measurements were performed. Left ventricle and thoracic aorta were removed for histological evaluations and to assess the expression of transforming growth factor beta (TGF-beta), tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6). Results: Carvedilol, nebivolol or amlodipine induced a greater reduction of carotid BP, short-term BPV and echocardiography parameters than atenolol in SHR rats. Carvedilol, nebivolol and amlodipine were more effective than atenolol in the prevention of cardiac hypertrophy, and cardiac and aortic collagen deposit. Carvedilol and nebivolol, but not atenolol, reduced the expressions of fibrotic and inflammatory biomarkers - TGF-beta, TNF-alpha and IL-6 - in SHR rats to a similar extent to that of amlodipine. Conclusion: Chronic treatment with carvedilol or nebivolol attenuates carotid BP and short-term BPV, and reduces target organ damage in SHR to a greater extent than atenolol. Our findings suggest that the lower cardiovascular protection of nonvasodilating beta-blockers, as atenolol, in hypertension must not be translated to third-generation beta-blockers.