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).

Introduction: Thiazide diuretic is a classic drug used to treat elevated arterial pressure (AP). However, their neuroinflammatory effects are limited when compared with other therapies. Objective: To compare the effect of hydrochlorothiazide (HCTZ) alone or combined with concurrent exercise training (aerobic+resistance, CET) on mechanisms of AP control and on inflammatory and redox balance in hypertensive postmenopausal rats. Methods: Female spontaneously hypertensive rats were distributed into sedentary (S) and ovariectomized groups: sedentary (OS), sedentary treated with HCTZ (OSH), trained (OT) and trained treated with HCTZ (OTH). HCTZ treatment (30 mg/kg) and CET (40-60% maximal capacity, 3 days/wk) were conducted for 8wks. AP was directly recorded at rest and after vasopressor system blockade (vasopressin antagonist, losartan and hexamethonium). Inflammation and oxidative stress were evaluated in cardiac tissue. Results: Trained groups presented higher exercise tests performance. Systolic (OT:178±18 and OTH:178±17 vs. OS:205±15) and mean AP (mmHg) (OTH:153±17 vs. OS:176±16) were reduced in trained groups. CET promoted an increase in both bradycardic and tachycardic responses of baroreflex sensitivity and a reduction in AP variability indexes in relation to OS group. After sympathetic blockade, AP (mmHg) reduction was higher in OS group (-75.7±19.2 vs. S:-53.2±12.6 and OTH:-49.8±12.4). In addition, IL-10 (OTH vs. OS and OSH) and IL-10/TNF-alpha ratio (OTH vs. S, OS, OSH and OT) were higher in OTH group. OS group showed increased NAPDHoxidase and reduced catalase (vs. S); however, these changes were not observed in OTH group. Negative correlation was observed between sympathetic vascular modulation and IL/TNF-alpha ratio (p<0.001, r:-0.6). Conclusions: We concluded that CET alone or combined with HCTZ are more efficient approaches than HCTZ to reduce AP and improve AP control of circulation. Specifically, the combination HCTZ plus CET induces additional positive adaptations on physical, autonomic, inflammatory and redox balance. These results highlight the key role of exercise in the management of HTN, probably impacting on the quality of life and reducing the residual risk in post menopause. Grants: FAPESP (2019/06277-0).