Apelin activates l-arginine/nitric oxide synthase/nitric oxide pathway in rat aortas

Apelin was recently found to be an inotropic polypeptide in isolated rat hearts, and intravenous injection of apelin can induce a transient decrease in blood pressure. To illustrate the mechanism of apelin-induced vasodilation, we observed the in vitro effects of apelin on the l-arginine (l-Arg)/nitric oxide (NO) pathway in the incubated, isolated rat aorta. Apelin stimulated vascular NO2− product and NOS activation in a concentration- and time-dependent manner. Compared with no apelin treatment, incubation with apelin (10−9, 10−8, and 10−7mol/L) increased NO2− product by 33%, 46%, and 69% (all p<0.01), respectively, and Ca2+-dependent constitutive NOS (cNOS) activity by 200%, 460%, and 550% (all p<0.01), respectively. However, Ca2+-independent NOS (iNOS) activity was not significantly altered (p>0.05). Apelin incubation (10−9, 10−8, and 10−7mol/L) increased l-Arg uptake by 130%, 180%, and 240% (all p<0.01), respectively. The mRNA level of cationic amino acid transporters, CAT-1 and CAT-2B, in rat aortic tissues treated with 10−7mol/L apelin was increased by 110% and 128%, respectively (both p<0.01). Incubation with 10−7mol/L apelin elevated eNOS mRNA and protein levels, by 53% (p<0.05) and 319% (p<0.01), respectively. Collectively, these results demonstrate that apelin directly activated the vascular l-Arg/NOS/NO pathway, which could be one of the important mechanisms of apelin-regulated vascular function.