Nitric oxide as a key mediator of vascular actions of atrial natriuretic peptide in spontaneously hypertensive rats.

CANIFFI CAROLINA; ELESGARAY ROSANA; RODRIGUEZ IERASE DANIELA; SAVIGNANO LUCÍA; AGUIRRE SOFÍA; ARRANZ CRISTINA; COSTA MARÍA DE LOS ÁNGELES

Buenos Aires

Congreso; XVII Meeting ISHR Latin American Section, International Society for Heart Research.; 2009

International Society for Heart Research

In previous studies we have demonstrated that atrial natriuretic peptide (ANP) increases vascular nitric oxide synthase (NOS) activity in spontaneously hypertensive rats (SHR). The aim was to study receptors, signaling pathways and NOS isoforms involved in this interaction in aorta artery. NOS activity (using L-[U14C]-arginina as substrate) induced by ANP (1uM) was determined in presence of:  inducible (iNOS) and neuronal NOS (nNOS) inhibitors, cANP (4-23) (NPR-C natriuretic receptor agonist), NPR-A/B natriuretic receptor antagonist, 8Br-cGMP (stable analogue of cGMP), PKG, Gi protein and calmodulin inhibitors. Endotelial NOS (eNOS) expression was determined by Western blot. Results: iNOS and nNOS blockade did not modify NOS activity induced by ANP. The increase in NOS activity induced by cANP was lower than the observed with ANP. NPR-A/B blockade partially decreased ANP effect. NOS activation via ANP was totally inhibited by calmodulin inhibition and it was blunted when PKG or Gi were blocked. 8-Br-cGMP partially mimiked ANP effect. eNOS expression was not modified by ANP. Conclusion: ANP would interact with NPRA/B activating cGMP/PKG signaling and with NPR-C activating Gi protein. Through both pathways ANP would promote the activation of Ca2+-calmodulin dependent eNOS in aorta artery of SHR. (ANOVA, postest:Bonferroni)