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

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

Milan, Italia

Congreso; Seventeenth European Meeting on Hypertension.; 2007

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 NOsystem 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. ANP SHRANP WKYControlControl 481.4±8.9*^300.1±16.1^329.8±2.9*201.8±4.7Right Atria 455.6±13.7*^310.5±8.7^339.8±3.5*210.5±5.8Left Ventricle 488.6±8.3*^346.8±5.6^348.7±9.1*198.6±3.4Aorta Protocol I1 cANPcANPANP SHRANP WKYAG SHRAG 21.9±3.6%19.2±3.2%# 36.6±3.9%47.4±5.3%-17.8±2.1%*-13±2%Left 43.8±2.0%44.1±1.1%# 47.1±2.8%48.6±2.1%-7.5±1.2%* -5±1%Right Atria 19.5±2.0%18.7±2.5%# 39.9±5.8%76.9±11.4%-16.5±1.1%*-13±1%Aorta Protocol II2 Conclusion: 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.