The novel peptide apelin lowers blood pressure via a nitric oxide-dependent mechanism

Apelin is an endogenous ligand of the human orphan receptor APJ. We detected apelin-like immunoreactivity in the adipocytes, gastric mucosa, and Kupffer cells in the liver. We also detected apelin-like immunoreactivity localized within the endothelia of small arteries in various organs. Further, it was found that mean arterial pressure after the administration of apelin-12, apelin-13, and apelin-36 at a dose of 10 nmol/kg in anaesthetized rats was reduced by 26 +/- 5, 11 +/- 4, and 5 +/- 4 mm Hg, respectively. In the presence of a nitric oxide (NO) synthase inhibitor, the effect of apelin-12 on blood pressure was abolished. Furthermore, the administration of apelin-12. (10 nmol/kg) in rats produced a transitory elevation of the plasma nitrite/nitrate concentration from a basal level of 21.4 +/- 1.6 to 27.0 +/- 1.5 muM Thus, apelin may lower blood pressure via a nitric oxide-dependent mechanism. (C) 2001 Elsevier Science B.V. All rights reserved.