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

Abstract

Background: b-blockers are no longer considered as firstline antihypertensive drugs due to their lower cardioprotection. Method: Considering the differences in the pharmacological properties of b-blockers, the present work compared the effects of third-generation bblockers – 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 b (TGF-b), tumor necrosis factor-a (TNF-a) 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-b, TNF-a 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 b-blockers, as atenolol, in hypertension must not be translated to thirdgeneration b-blockers. Keywords: amlodipine, atenolol, blood pressure variability, carvedilol, nebivolol, spontaneously hypertensive rats, target organ damage Abbreviations: BP, blood pressure; BPV, blood pressure variability; CV, coefficient of variation; D. Post. WT, diastolic posterior wall thickness; HR, heart rate; ICF, interstitial collagen fraction; IL-6, interleukin-6; IVRT, isovolumic relaxation time; LVEDD, left ventricular end diastolic diameter; LV, left ventricular; LVWT, left ventricular wall thickness; SHR, spontaneously hypertensive rats; TGF-b, transforming growth factor b; TNF-a, tumor necrosis factor-a; TOD, target organ damage; TPGS, D-a-tocopheryl polyethylene glycol 1000 succinate; WKY, Wistar Kyoto