The apelin/APJ system in the regulation of vascular tone: friend or foe?

The apelin (APJ) receptor was originally cloned as a gene encoding a putative G protein-coupled receptor related to angiotensin receptor type I. To date, two endogenous peptide ligands for APJ have been identified: apelin and elabela/Toddler. The apelin/APJ system regulates blood pressure and vascular tone. The endothelial and smooth muscle apelin/APJ systems exert opposite actions in the regulation of vascular tone. Binding of apelin to endothelial APJ promotes the release of vasodilators, such as nitric oxide and prostacyclin, leading to vasodilation. Alternatively, binding of apelin to smooth muscle APJ induces vasoconstriction, although the molecular mechanisms of the apelin-induced vasoconstriction are poorly understood. Recently, a critical role for interaction of APJ with α1-adrenergic receptor in the apelin-induced vasoconstriction was reported. The action of apelin on vascular tone may depend upon blood vessel type or pathological condition. Although the apelin/APJ system could serve as a potential therapeutic target for hypertension and cardiovascular disease, the role of this system in various cell types appears to be complicated.