Vascular relaxation induced by C-type natriuretic peptide involves the ca2+/NO-synthase/NO pathway.
OBJECTIVE
C-type natriuretic peptide (CNP) and nitric oxide (NO) are endothelium-derived factors that play important roles in the regulation of vascular tone and arterial blood pressure. We hypothesized that NO produced by the endothelial NO-synthase (NOS-3) contributes to the relaxation induced by CNP in isolated rat aorta via activation of endothelial NPR-C receptor. Therefore, the aim of this study was to investigate the putative contribution of NO through NPR-C activation in the CNP induced relaxation in isolated conductance artery.


METHODS
Concentration-effect curves for CNP were constructed in aortic rings isolated from rats. Confocal microscopy was used to analyze the cytosolic calcium mobilization induced by CNP. The phosphorylation of the residue Ser1177 of NOS was analyzed by Western blot and the expression and localization of NPR-C receptors was analyzed by immunohistochemistry.


RESULTS
CNP was less potent in inducing relaxation in denuded endothelium aortic rings than in intact ones. L-NAME attenuated the potency of CNP and similar results were obtained in the presence of hydroxocobalamin, an intracellular NO0 scavenger. CNP did not change the phosphorylation of Ser1177, the activation site of NOS-3, when compared with control. The addition of CNP produced an increase in [Ca2+]c in endothelial cells and a decrease in [Ca2+]c in vascular smooth muscle cells. The NPR-C-receptors are expressed in endothelial and adventitial rat aortas.


CONCLUSIONS
These results suggest that CNP-induced relaxation in intact aorta isolated from rats involves NO production due to [Ca2+]c increase in endothelial cells possibly through NPR-C activation expressed in these cells. The present study provides a breakthrough in the understanding of the close relationship between the vascular actions of nitric oxide and CNP.
Department of Pharmacology, School of Medicine of Ribeirão Preto - University of São Paulo, São Paulo, Brasil.
Fernanda A
FA
Andrade
Department of Medicine - University of Ribeirão Preto, Ribeirão Preto, Brasil.
Carolina B A
CB
Restini
Department of Physics and Chemistry, Faculty of Pharmaceutical Sciences of Ribeirão Preto - University of São Paulo, São Paulo, Brasil.
Marcella D
MD
Grando
Department of Cellular and Molecular Pathology, School of Medicine of Ribeirão Preto - University of São Paulo, São Paulo, Brasil.
Leandra N Z
LN
Ramalho
Department of Physics and Chemistry, Faculty of Pharmaceutical Sciences of Ribeirão Preto - University of São Paulo, São Paulo, Brasil.
Lusiane M
LM
Bendhack
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology; D002118:Calcium / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D006879:Hydroxocobalamin / Q000494:pharmacology; D008297:Male; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D020098:Natriuretic Peptide, C-Type / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010656:Phenylephrine / Q000494:pharmacology; D010766:Phosphorylation; D051381:Rats; D017461:Receptors, Atrial Natriuretic Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology*
D020098:Natriuretic Peptide, C-Type; D010656:Phenylephrine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D017461:Receptors, Atrial Natriuretic Factor; D006879:Hydroxocobalamin; D002118:Calcium; D019331:NG-Nitroarginine Methyl Ester