IQUIMEFA   05518
INSTITUTO QUIMICA Y METABOLISMO DEL FARMACO
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Relevance of the interaction between atrial natriuretic peptide and nitric oxide system in a model of spontaneous hypertension.
Autor/es:
CANIFFI CAROLINA; ELESGARAY ROSANA; MAC LAUGHLIN MYRIAM; VISINTINI JAIME MARIA FLORENCIA; FINELLA SEBASTIÁN; BURGER CAROLINA; BALASZCZUK ANA MARÍA; ARRANZ CRISTINA; COSTA MARIA DE LOS ANGELES
Lugar:
Miami, USA.
Reunión:
Congreso; Scientific Sessions of the Inter-American Society of Hypertension and the Consortium for Southeastern Hypertension Control.; 2007
Institución organizadora:
Inter-American Society of Hypertension
Resumen:
Atrial natriuretic peptide(ANP) and nitric oxide(NO)induce diuresis, natriuresis and diminish vascular tone. We showed NO-system is involved in ANP hypotensive effect in normotensive rats. The objective was to study changes in systolic blood pressure(SBP) and NO-system induced by ANP in adult spontaneously hypertensive rats(SHR)and the role of the inducible NO synthase (iNOS). Methods: Protocol I: SHR and Wistar Kyoto rats(WKY) divided into two groups were infused with saline (Control,C,1hour,0.05ml/min)or ANP (1hour,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 left ventricle (Ventr)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).               C WKY        C SHR            ANP WKY    ANP SHR Aorta   198.6±3.4      348.7±9.1*     346.8±5.6^     488.6±8.3*^ Atria    201.8±4.7      329.8±2.9*     300.1±16.1^   481.4±8.9*^ Ventr  210.5±5.8         339.8±3.5*     310.5±8.7^     455.6±13.7*^ *p<0.01 vs WKY;^p<0.01 vs C.In all tissues, SHR NOS activity was higher than WKY, and ANP treatment increased NOS activity in both groups.Protocol II: Results are expressed as percentage of decrease or increase respect to the NOS basal activity.*p<0.01 vs WKY same treatment,#p<0.01 vs ANP.           AG WKY  AG SHR     ANP WKY  ANP SHR   cANP WKY  cANP SHR Aorta     -13±1%  -17±1%*     77±11%   40±6%*     9±3%#   20±2# Atria     -5±1%   -8±1%*      49±2%    47±3%     44±1%#   44±2%# Ventr     -13±2%  -18±2%*     47±5%    37±4%*    19±3%#   22±4%# Conclusion: ANP infusion induced a decrease of SBP, which was associated to an increased NOx excretion. In addition, ANP induced an increase of NOS activity in heart and aorta, indicating that peptide increases de production of NO in the studied tissues. Thus, iNOS inhibition diminished basal NOS activity in both groups and these decrese was higher in SHR than WKY, in all tissues, suggesting a higher basal iNOS activity in SHR. ANP and the NPR-C specific agonist provoked similar increases in atrial NOS activity, indicating that, in atria, 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.