Aim: 

Increasing number of novel neuropeptides have been proposed to regulate several cardiovascular events. Urocortin was described to induce a strong coronary vasodilatation; besides urotensin-II was shown as the most potent mammalian vasoconstrictor identified so far. Moreover, store-operated channels activation and Ca²⁺ independent phosholipase A2 (iPLA2) have been shown to play a critical role in the regulation of vascular tone. The aim of this study was to characterize the signalling pathway involved in Urotensin-II and Urocortin regulation of coronary vascular tone Ca²⁺ independent phosholipase A2.

Methods: 

Wistar Rats coronary arteries were cleaned, cut in rings (~2 mm) and mounted on a small-vessel myograph to measure isometric tension. The intracellular Ca²⁺ measurement was studied in isolated coronary smooth muscle cells pre-incubated with Fura 2-AM; and the fluorescence was recorded and analyzed using an InCytIm2 imaging system.

Results: 

We observed that urotensin-II and urocortin has differential effects on vascular tone. Urotensin-II induced a dose dependent vasoconstriction which was sensitive to the iPLA2 and the store operated channels inhibitors, suggesting a critical role of those channels in vascular tone modulation by urotensin-II. Besides, urocortin induced a strong vasodilatation of the artery by the inhibition of iPLA2 and the consequent store operated channels via cAMP dependent pathway.

Conclusion: 

Our data show an important role of novel neuropeptides in the regulation of vascular tone which differentially modulate iPLA2 activation of store operated channels pathway.

Acknowledgements: 

This study was supported by Consejería de Innovación y Ciencias de la Junta de Andalucía "P0-CVI-3913". T.S is a "Ramon y Cajal" Researcher and A.D.R is a fellow of Consejería de Innovación y Ciencias de la Junta de Andalucía "P06-CTS-01711".