Liraglutide improves antioxidant defense in hearts of spontaneously hypertensive female rats independently of changes in blood pressure in a pre-clinical model of menopause

Abstract

Liraglutide (LIRA) is an agonist of the GLP-1 receptor used in the treatment of type 2 diabetes with a cardioprotective effect, although little is known about the effects of LIRA in post-menopause. We aimed to evaluate the effects of LIRA in the cardiovascular system of ovariectomized spontaneously hypertensive rats (SHR). SHR rats were separated into two groups: ovariectomized (saline) and ovariectomized + liraglutide (0.6 and 1.2 mg/kg for 4+4 weeks, respectively). Systolic blood pressure (SBP) was indirectly evaluated at the beginning and end of treatment. Diastolic, systolic, and mean blood pressure were evaluated in the carotid artery of anesthetized animals, while left ventricle systolic blood pressure (LVSBP) and left ventricle derivatives (-dP/dt; +dP/dt) were evaluated in the left ventricle. An oral glucose tolerance test (GTT) was conducted. Antioxidant enzymes and calcium-handling proteins were analyzed in heart tissue by western blot. Treatment with LIRA increased the expression of antioxidant enzymes (superoxide dismutase (SOD2) and catalase). No changes were observed in the GTT, cardiac hemodynamics, blood pressure, and calcium-handling protein expression. A decrease in visceral fat depot was observed without changes in final body weight. LIRA induced an antioxidant subclinical effect in ovariectomized SHR female rats without changing glucose metabolism and cardiac blood pressure.

Figure 1. Glucose oral tolerance test results over time (h). A, Representative curves of the ovariectomized control group (O) and ovariectomized group treated with liraglutide (OL). B, Area under the curve (AUC). Data are reported as means±SE. The difference between groups was evaluated by Student's t-test. The data presented a parametric distribution. ns: non-significant.

Figure 2. Relative protein expression in hearts of ovariectomized rats treated (OL) or not (O) with liraglutide. A, Superoxide dismutase 1 (SOD1; P=0.61); B, superoxide dismutase 2 (SOD2; P=0.04); C, catalase (CAT; P=0.02); D, phospholambam (PBL; P=0.05); E, SERCA (P=0.84); F, SERCA/PBL ratio (P=0.0858). The expression of each protein was normalized by GAPDH. Data are reported as means±SE. *P<0.05, Student's t-test; ns: non-significant.