Diuretic Associated With Concurrent Exercise Promotes Additional Physical, Autonomic and Inflammatory Adaptations in Hypertensive Rats Submitted to Ovarian Hormone Privation

Abstract

Objective:To evaluate the effects of hydrochlorothiazide (HCTZ) combined or not with concurrent exercise training on physical capacity and neurohumoral mechanism of blood pressure (BP) control in a model of hypertension and menopause.Design and method:Female spontaneously hypertensive rats were allocated into sedentary (S) and ovariectomized groups: sedentary (OS), sedentary treated with HCTZ (OSH) and trained treated with HCTZ (OTH). Ovariectomy procedure was performed at initial of protocol. HCTZ (30 mg/kg) was administrated orally in drinking water. Aerobic and resistance exercises (40–60% maximal capacity) were conducted 3 days/wk for 8 weeks. BP, heart rate and its variabilities were nalysed using signals of direct recording of BP. Vasopressin receptor antagonist, losartan and hexamethonium were sequentially injected to evaluate vasopressor system. Inflammatory profile was evaluated.Results:Systolic and mean BP (mmHg) were lower in OTH (178 ± 17 and 153 ± 17, respectively) compared with OS group (205 ± 15 and 176 ± 16, respectively). Treadmill (OTH vs. OSH) and ladder physical test performance (OTH vs. OS, OS and OSH) were higher in OTH group. Baroreflex sensitivity (bpm/mmHg) was lower in OS group (vs. S) and both bradycardic (OTH:- 1.6 ± 0.3 vs. OS:-0.6 ± 0.3) and tachycardic response (OSH:-2.2 ± 0.7 and OTH:-2.4 ± 0.8 vs. OS:- 1.3 ± 0.4) were improved after HCTZ treatment. OTH showed higher (high-frequency band: OTH:77.8 ± 4.9 vs. OS:69.8 ± 4.0nu) and lower cardiac sympathetic modulation (low-frequency band: OTH:22.2 ± 4.9 vs. OS:30.2 ± 4.0nu) and LF/HF ratio (OTH:0.30 ± 0.08 vs. OS:0.45 ± 0.09). In addition, reduced variance (OTH:30.3 ± 10.5 vs. OS:60.1 ± 13.1) and low-frequency band of systolic BP (mmHg2) (OTH:6.2 ± 5.2 vs. S:16.3 ± 6.7, OS:18.8 ± 6.1 and OSH:15.8 ± 5.5) was observed in trained group. Drop in BP (mmHg) after hexamethonium was higher in OS group (- 75.7 ± 19.2 vs. S:-53.2 ± 12.6, OSH:-54.9 ± 9.0 and OTH:-49.8 ± 12.4). IL-10 (OTH:78.1 ± 17.3 vs. OS:52.8 ± 23.2 and OSH:45.1 ± 10.6) and IL-10/TNF-a ratio (OTH:1.99 ± 0.07 vs. S:1.32 ± 0.21, OS: 1.18 ± 0.12 and OSH:1.18 ± 0.27) was higher in trained group.Conclusions:We concluded that HCTZ combined with exercise training is more efficient than HCTZ alone to improve BP control, probably due to a better adjustment on autonomic modulation and inflammation profile, in addition to induce cardiofunctional benefits. This data reinforces the key role of exercise in the attenuation of hypertension-induced damage in menopaused rats. Grants: FAPESP (2019/06277–0).