Role of nitric oxide as a key mediator on cardiovascular actions of atrial natriuretic peptide in spontaneously hypertensive rats

COSTA MARÍA DE LOS ÁNGELES; ELESGARAY ROSANA; CANIFFI CAROLINA; FELLET ANDREA; MAC LAUGHLIN MYRIAM; ARRANZ CRISTINA

AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY

AMER PHYSIOLOGICAL SOC

Año: 2010 p. 778 - 786

0363-6135

Objective: to study atrial natriuretic peptide (ANP) effects on mean arterial pressure (MAP) and cardiovascular nitric oxide (NO) system in spontaneously hypertensive rats (SHR), investigating receptors and signaling pathways involved. Methods: In vivo: SHR and Wistar Kyoto rats (WKY) were infused with saline (0.05ml/min) or ANP (0.2µg/Kg.min) during 1 hour. MAP and nitrites and nitrates excretion(NOx) were determined. NO synthase(NOS) activity and endothelial(eNOS), neuronal(nNOS) and inducible(iNOS) NOS expression were measured in heart and aorta. In vitro: Heart and aortic NOS activity induced by ANP was determined in presence of: iNOS and nNOS inhibitors, NPR-A/B natriuretic receptors blocker, Gi protein and calmodulin inhibitors. Results: ANP diminished MAP and increased NOx in both groups. Cardiovascular NOS activity was higher in SHR than WKY. ANP increased NOS activity, but activation was lower in SHR than WKY. ANP had no effect on NOS isoforms expression. NOS activity induced by ANP was not modified by iNOS and nNOS inhibitors. NPR-A/B blockade blunted NOS stimulation via ANP in ventricle and aorta, but not in atria. Cardiovascular NOS response to ANP was reduced by Gi protein and calmodulin inhibitors in both groups. Conclusions: In atria, ventricle and aorta, ANP interacts with NPR-C receptors, activating Ca-calmodulin eNOS through Gi protein. In ventricle and aorta, NOS activation also involves NPR-A/B. NOS response to ANP was impaired in heart and aorta of SHR. Impaired NO-system response to ANP in hypertensive animals, involving alterations in the signaling pathway, could participate in maintenance of high blood pressure in this model of hypertension.