Abstract P3060: Cardiovascular Regulatory Actions of Apelin in Normotensive Rats: Central versus Peripheral Effects

Abstract

Apelin and its receptor APJ are expressed in both cardiovascular system (CVS) and central nervous system (CNS). Although the apelin/APJ system have already been shown to be involved in cardiovascular homeostasis, the mechanisms in the regulation of CVS are still not fully clear. Thus, this study was undertaken to compare central versus peripheral effect of apelin in the regulation of hemodynamic in SD rats. The chronic recording of blood pressure (BP) and heart rate (HR) were performed using radiotelemetry. Chronic infusion of apelin-13 (100 μg/kg/day) into the lateral cerebral ventricle using osmotic minipumps significantly elevated BP by 15.2±0.9 mmHg, The water intake was also increased from 38±2 to 51±3 ml/day before and after brain infusion of apelin-13. However, the HR was not significantly altered. Furthermore, this chronic pressor effect of apelin-13 was associated with a dramatic increase in the number of Fra-LI positive neurons within the paraventricular nucleus (PVN) and nucleus tractus solitarii (NTS), which were measured with immunohistochemistry using c-Fos antibodies, suggesting an elevated neuronal activity in the brain cardiovascular regulatory areas. Thus, apelin-13 was microinjected into the PVN to confirm the neuronal effect on the BP. The BP of rats was recorded using femoral arterial cannulation. The results demonstrated that acute microinjection of apelin-13 into the PVN significantly increased BP and HR. In peripheral CVS, acute intravenous injections of apelin-13 induced a transient reduction in BP by 25±3 mmHg as expected. Surprisingly, in the same group of rats, the cardiac contractility (dP/dt Max from 8131±512 to 7822±484 mmHg/s) was not significantly altered by apelin-13. In addition, chronic subcutaneous infusion of apelin-13 did not significantly alter either BP or cardiac contractility, which were detected with ratiotelemetry and echocardiography in rats. In conclusion, peripheral administration of apelin-13 only induced a transient decrease in BP without chronic BP regulatory and cardiotonic effects. In contrast, central application of apelin-13 leaded to a chronic elevation in the BP, suggesting that apelin-13 acting as an important neuropeptide in the CNS may contribute to the long-term control of BP.