The effect of glucagon-like peptide-1 receptor agonist (GLP1RA) on hypertensive-induced heart failure with preserved ejection fraction and hypertensive cardiomyopathy

Abstract

ABSTRACTEmerging preclinical data suggest that glucagon-like peptide-1 receptor agonist (GLP1RA) possesses cardioprotective properties against the pathophysiology of hypertension (HT). We sought to unravel the potential therapeutic application of GLP1RA in a clinically relevant large animal model of hypertensive cardiomyopathy (hCMP). A combination of angiotensin II (Ang II) and deoxycorticosterone acetate (DOCA) pellets were used to induce sustained HT status and establish hCMP in porcine model. Changes in cardiac echocardiography, invasive hemodynamic parameters, neurohumoral biomarkers and inflammation-related cytokines were investigated in 23 adult pigs, among which 6 were serving as control, 9 were induced with HT, and the remaining 8 were HT-induced with GLP1RA treatment. Eight weeks after the study initiated, HT pigs have developed sustained high blood pressure (BP) at both systole and diastole. Phenotype of hCMP has also become significant as impairment in systolic/diastolic function, left ventricular remodeling and cardiac hypertrophy was determined by echocardiogram and invasive hemodynamics. Additionally, blood norepinephrine (NE) content, venoarterial NE gradient and pro-inflammatory cytokines in HT pigs were increased. GLP1RA treatment halted the elevation in BP, left ventricular remodeling and cardiac hypertrophy development; preserved the left ventricular systolic/diastolic function; reduced the venoarterial NE gradient as well as the pro-inflammatory cytokines at 18 weeks in pigs with hCMP. Our results demonstrate that GLP1RA treatment has a remarkable effect on BP decrease, inflammation suppression and left ventricular function improvement. Thus, we provide novel insight into the therapeutic potential of GLP1RA in HT-induced heart failure in a large animal model of hCMP.