Secretoneurin induces endothelium-dependent relaxation of the porcine coronary artery

Abstract

Secretoneurin is a part of the peptide encoded by the Secretogranin II gene. Secretoneurin enhances the adhesion and transendothelial migration properties of monocytes. In addition, in regenerated endothelium, the expression of the Secretogranin II gene is up-regulated. The objective of the present study was to examine the effects of Secretoneurin on the vascular reactivity. Isometric tension of rings with or without endothelium from porcine coronary arteries was measured in conventional organ chambers. Secretoneurin did not induce contraction, but in preparations contracted by the TP-receptor agonist U46619 it caused relaxation. This relaxation was endothelium-dependent and reduced by the nitric oxide synthase inhibitor Nomega-nitro-L-arginine methyl ester (L-NAME). It was abolished by combined incubation with L-NAME and the cyclooxygenase inhibitor indomethacin. By contrast the relaxation to secretoneurin was not affected by TRAM 34 and UCL 1684. These results suggest that secretoneurin induces relaxation by activation of both endothelial nitric oxide synthase and cyclooxygenase, with the nitric oxide pathway playing a more dominant role.