Effect of endogenous apelin receptor ligands on vascular contractility and investigation of possible effect mechanisms

The apelinergic system is very important due to its cardiovascular effects, and it has a high treatment potential in cardiovascular diseases, which are common causes of morbidity and mortality worldwide. In this study, the effects of apelin and elabela, which are the components of the apelinergic system, on vascular contractility and their mechanisms of action were investigated. Vascular rings obtained from the thoracic aorta of the male Wistar Albino rats were placed in an isolated organ bath system. After the equilibration period, pyroglutamyl apelin-13 ([Pyr1]apelin-13) or elabela-32 (Ela-32) was applied cumulatively to the vessels pre-contracted with phenylephrine in the plateau phase to investigate the effects on vascular tension. The protocol was repeated in the presence of specific pathway inhibitors to demonstrate their mechanism of action. For this purpose, apelin receptor (APJ), endothelial nitric oxide synthase (eNOS), AMPactivated protein kinase (AMPK), cyclooxygenase (COX), mitogen-activated protein kinase (MAPK), and potassium channel inhibitors were used. [Pyr1]apelin-13 induced a dose-dependent relaxation in the thoracic aorta of the rat pre-contracted with phenylephrine. Ela-32 also showed a dose-dependent vasodilator effect. It has been observed that both active ingredients act as a vasodilator through their common receptor, APJ. It has been determined that nitric oxide (NO), AMPK, prostanoids, and potassium channels play a role in the vasodilator effect of [Pyr1]apelin-13. It has been shown that AMPK, prostanoids, and potassium channels participate in the vasodilator effect of Ela-32. The vasodilator effect level of Ela-32 in rat thoracic aorta was found to be higher than [Pyr1]apelin-13. In conclusion, it was determined that APJ, NO, AMPK, prostanoids, and potassium channel activation play a role in the vasodilator activity of the apelinergic system. Ela-32 has been shown to cause a higher level of vasodilation than [Pyr1]apelin-13. It is thought that apelinergic system elements may be an important treatment alternative in hypertensive diseases due to their prominent vasodilator effects. Keywords: apelin, elabela, NO, potassium channel, vasodilation