EAdministration of Apelin modulates myocardial expression of Apelin-APJ and improves right ventricular performance in MCT-induced pulmonary hypertension

Abstract

Apelin (AP) is the endogenous vasoactive ligand of APJ receptor. It is widely expressed in the heart and lungs and has important cardiovascular functions such as endothelium-dependent vasodilatation and positive inotropic effect. However, the role of apelin-APJ system in pulmonary hypertension (PH) remains to be clarified. Objective: To evaluate the chronic effects of apelin in: 1) right ventricular (RV) myocardial function; 2) cardiac expression of apelin and APJ in healthy and MCT-PH rats Wistar rats were randomly injected with MCT (60mg/kg, sc) or vehicle (CTR, day 0). One week later, half of these animals were randomly treated with Pyr-apelin-13 (200µg/kg/day, ip) or a similar volume of vehicle. The study resulted in 4 groups: CTR; AP; MCT and MCT+AP. At day 24, animals were instrumented to record RV peak systolic (Pmax) pressures, dP/dtmax, dP/dtmin and time constant Tau. Also, heart and lungs were weighted and samples collected for relative quantification of mRNA by real-time RT-PCR. Results: seen table.CTR AP MCT MCT+AP

Analysis of heart rate variability in a rat model of induced pulmonary hypertension

“…The dose of MCT (60 mg/kg) used was associated at 4 weeks with scarce signs of cardiac failure and low mortality, in agreement with other reports [10,[15][16][17]. At the end of the study, rats were still used for experiments on acute hypoxia and anoxia, recently reported elsewhere [14].…”

“…To our knowledge, such a study has never been reported. The used rat model has been extensively studied and biochemically, physiologically and histo-pathologically characterized by our group [10,15,16,20]. It is of particular interest in experimental studies on pulmonary hypertension and right ventricular heart failure [2,15,17,20,24,33], but it may also help to understand some human fetal pathological conditions associated to progressive heart failure and growth restriction, characterized by left and right ventricular increased afterload, progressing to right heart failure, with tricuspid valve failure and abnormal ductus venosus blood flow [25].…”