P099 EXERCISE TRAINING FURTHER ATTENUATES BLOOD PRESSURE VARIABILITY AND RENAL DAMAGE IN HYDROCHLOROTHIAZIDE TREATED-HYPERTENSIVE AND POSTMENOPAUSAL RATS

Background and Objective: Considering that blood pressure variability (BPV) has been associated with damage to target organs such as the kidney, this study aimed to investigate the effects of hydrochlorothiazide (HCTZ) combined with exercise training (CET) on BPV, as well as renal tissue morphology, function, inflammation, and oxidative stress. Methods: Female spontaneously hypertensive rats (SHR) were divided into 4 ovariectomized groups (n=5-6/group): sedentary (OS), sedentary + HCTZ (OSH), trained (OT), and trained + HCTZ (OTH). Both HCTZ (3 mg/kg) and CET (3 days/week) were administered for 8 weeks. Blood pressure was directly recorded for BPV analysis. Results: Renal function, morphology, inflammation and oxidative stress were assessed. The OSH, OT, and OTH groups had lower systolic BP (OSH: 189±13; OT: 179±5; OTH: 174±15 mmHg) compared to the OS group (208±15 mmHg). Only the combination of the drug with CET promoted a reduction in BPV variance. The HCTZ-treated groups showed lower plasma creatinine levels and increased creatinine clearance compared to the OS group. Treated groups showed a reduction in fields of 51–100% of interstitial tubule fibrosis when compared to the OS group; and the OTH group also showed reduction in fields in the range of 26–50% vs. other groups. The HCTZ-treated groups showed a reduction in protein oxidation. Renal catalase and IL10/TNF-alpha ratio were increased in the OTH group. Positive correlations were obtained between SBP variance and SBP (r=0.72), plasma creatinine (r=0.58), and levels of TNF-α (r=0.69), hydrogen peroxide (r=0.61), and protein oxidation (r=0.66) in renal tissue. Conclusions: Our results highlight the enhanced efficacy of the combination of HCTZ and CET compared to the use of either drug alone in the model studied. This combination effectively reduced BPV, resulting in beneficial changes in renal inflammatory and redox profiles, inducing morphological and functional benefits in hypertensive ovariectomized rats. Financial support: FAPESP (2022/04050-1), CNPq, CAPES-PROSUP, UNINOVE.