Enalapril associated with combined training is more effective in reducing SBP and improve baroreflex sensitivity than drug therapies alone in hypertensive rats

Abstract

High blood pressure is the leading risk factor to development of cardiovascular disease worldwide. Diuretic and angiotensin‐converting enzyme blockers treatment is widely used for its efficiency in reducing blood pressure (BP). Combined physical training (aerobic + resistance) is recommended for hypertensive patients; however, it is not yet clear whether the combination of antihypertensive treatment with this training modality results in additional benefits. Therefore, the aim of this study was to compare the effects of combined training with different drug treatments on systolic BP (SBP) and baroreflex sensitivity (BRS) of spontaneously hypertensive rats (SHR). Twenty‐eight males SHR rats were divided into four groups (n=7/group): HS (sedentary hydrochlorothiazide), HT (trained hydrochlorothiazide), ES (sedentary enalapril) and ET (trained enalapril). Drugs were administered in drinking water (enalapril 3 mg/kg/day and hydrochlorothiazide 30 mg/kg/day). All groups underwent exercise testing before and after 2 months. The trained groups performed combined training 3 times a week, being aerobic and resistance at same session, moderate intensity. The SBP was analyzed by caudal plethysmography before starting the drugs and 24h after the last training session. BRS was analyzed by response to phenylephrine and sodium nitroprusside. Both trained groups increased maximal aerobic exercise test (p<0.0001) and resistance exercise test (HT vs. HS, p=0.02; ET vs. ES, p<0.0001) versus the sedentary groups at the end of the protocol. There was no difference in the initial SBP between the groups (HS 176 ± 4.3, HT 175 ± 3, ES 173 ± 1.4 and ET 183 ± 3 mmHg). There were reductions in SBP in the HT (161 ± 1.3 mmHg), ES (159 ± 4.4 mmHg) and ET groups (147 ± 3.3 mmHg) at the end of the protocol. In addition, the trained group associated with enalapril treatment further reduced SBP when compared to the trained hydrochlorothiazide group (ET vs. HT, p = 0.02). Regarding BRS, there was no difference in tachycardic response between groups; however, ET group (‐2.8 ± 0.5 bpm/mmHg) showed increased bradycardic responses comparing with ES group (‐1.8 ± 0.1 bpm/mmHg). Therefore, the data support that the association of combined exercise training with enalapril treatment and is more effective in reducing SBP and improving BRS than the combination with hydrochlorothiazide treatment. It is noteworthy that the training proposed in this study was performed only three times a week, getting closer to clinical recommendations, and being enough for induce additional benefits to classical drug therapies in functional capacity and blood pressure control in an experimental model of hypertension.