Nitric oxide system activation induced by atrial natriuretic peptide: mechanisms involved in experimental hypertension.

COSTA MARIA DE LOS ANGELES; ELESGARAY ROSANA; CANIFFI CAROLINA; BURGER CAROLINA; FINELLA SEBASTIÁN; VISINTINI JAIME MARIA FLORENCIA; FELLET ANDREA; BALASZCZUK ANA MARÍA; ARRANZ CRISTINA

Milán, Italia

Congreso; Seventeenth European Meeting on Hypertension.; 2007

European Society of Hypertension

Two important factors involved in arterial blood pressure regulation are atrial natriuretic peptide (ANP) and nitric oxide (NO). In previous studies we showed NO-system activation mediates ANP hypotensive and diuretic actions in normotensive rats. Objective: the aim was to study ANP effects on systolic blood pressure (SBP)and NO-system in adult spontaneously hypertensive rats (SHR) and the role of the inducible NO synthase (iNOS) in this model. Desing and method: Protocol I: SHR and Wistar Kyoto rats (WKY) divided into two groups were infused with saline (Control, C, 1 hour, 0.05ml/min) or ANP (1 hour, 0.2µg/Kg.min). SBP (mmHg) was recorded and urine samples were recollected for nitrites and nitrates (NOx, nmol/min.100g) determination. NOS activity was measured in aorta and heart. Protocol II: Aorta, right atria and ventricle from SHR were removed for determination of NOS catalytic activity (pmol L-[U14C]-citrulline/g tissue.min) after addition of: ANP (1µM), cANP (4-23) (NPR-C agonist,1µM) or aminoguanidine (AG, iNOS inhibitor, 1µM). Results: Protocol I: ANP diminished SBP in SHR (C:198±4, ANP:165±7^; ^p<0.01 vs C) and increased NOx in both groups (WKY: C: 1.07±0.20, ANP: 1.54±0.04^; SHR: C: 1.43±0.05*; ANP:2.35±0.11*^; *p<0.01 vs WKY; ^p<0.01 vs C). ANP infusion induced a decrease of SBP, which was associated to an increased NOx excretion. ANP induced an increase of NOS activity in heart and aorta. Thus, iNOS inhibition diminished basal NOS activity in both groups and these decrease was higher in SHR than WKY, suggesting a higher basal iNOS activity in SHR. ANP and the NPR-C specific agonist provoked similar increases in atrial NOS activity, indicating that ANP would only interact with NPR-C to stimulate NOS activity. In aorta and ventricle, NOS activation via ANP would involve, not only the interaction with NPR-C, but also NPR-A and/or in SHR. NOS activation induced by ANP via NPR-C would not appear to be altered in this model of hypertension. Alterations in the interactions between both systems, ANP and NO, would be involved in the development and/ or the maintenance of arterial hypertension in this experimental model. ANP infusion induced a decrease of SBP, which was associated to an increased NOx excretion. ANP induced an increase of NOS activity in heart and aorta. Thus, iNOS inhibition diminished basal NOS activity in both groups and these decrease was higher in SHR than WKY, suggesting a higher basal iNOS activity in SHR. ANP and the NPR-C specific agonist provoked similar increases in atrial NOS activity, indicating that ANP would only interact with NPR-C to stimulate NOS activity. In aorta and ventricle, NOS activation via ANP would involve, not only the interaction with NPR-C, but also NPR-A and/or in SHR. NOS activation induced by ANP via NPR-C would not appear to be altered in this model of hypertension. Alterations in the interactions between both systems, ANP and NO, would be involved in the development and/ or the maintenance of arterial hypertension in this experimental model. ANP infusion induced a decrease of SBP, which was associated to an increased NOx excretion. ANP induced an increase of NOS activity in heart and aorta. Thus, iNOS inhibition diminished basal NOS activity in both groups and these decrease was higher in SHR than WKY, suggesting a higher basal iNOS activity in SHR. ANP and the NPR-C specific agonist provoked similar increases in atrial NOS activity, indicating that ANP would only interact with NPR-C to stimulate NOS activity. In aorta and ventricle, NOS activation via ANP would involve, not only the interaction with NPR-C, but also NPR-A and/or in SHR. NOS activation induced by ANP via NPR-C would not appear to be altered in this model of hypertension. Alterations in the interactions between both systems, ANP and NO, would be involved in the development and/ or the maintenance of arterial hypertension in this experimental model. ANP infusion induced a decrease of SBP, which was associated to an increased NOx excretion. ANP induced an increase of NOS activity in heart and aorta. Thus, iNOS inhibition diminished basal NOS activity in both groups and these decrease was higher in SHR than WKY, suggesting a higher basal iNOS activity in SHR. ANP and the NPR-C specific agonist provoked similar increases in atrial NOS activity, indicating that ANP would only interact with NPR-C to stimulate NOS activity. In aorta and ventricle, NOS activation via ANP would involve, not only the interaction with NPR-C, but also NPR-A and/or in SHR. NOS activation induced by ANP via NPR-C would not appear to be altered in this model of hypertension. Alterations in the interactions between both systems, ANP and NO, would be involved in the development and/ or the maintenance of arterial hypertension in this experimental model.