Relevance of the interaction between atrial natriuretic peptide and nitric oxide system in a model of spontaneous hypertension.

CAROLINA CANIFFI; ROSANA ELESGARAY; MYRIAM MAC LAUGHLIN; MARÍA FLORENCIA VISINTINI JAIME; SEBASTIÁN FINELLA; ANA CAROLINA BURGER; ANA MARIA BALASZCZUK; CRISTINA ARRANZ; MARÍA ÁNGELES COSTA

Miami, USA

Congreso; Scientific Sessions of the Inter-American Society of Hypertension and the Consortium for Southeastern Hypertension Control; 2007

Inter-American Society of Hypertension

Atrial natriuretic peptide(ANP) and nitric oxide(NO)induce diuresis,natriuresis and diminish vascular tone. We showed NO-system isinvolved in ANP hypotensive effect in normotensive rats. The objectivewas to study changes in systolic blood pressure(SBP) and NO-systeminduced by ANP in adult spontaneously hypertensive rats(SHR)and therole of the inducible NO synthase (iNOS). Methods: Protocol I: SHR andWistar Kyoto rats(WKY) divided into two groups were infused withsaline(Control,C, 1hour, 0.05ml/min) or ANP (1hour,0.2μg/Kg.min). SBP(mmHg)was recorded and urine samples were recollected for nitrites andnitrates(NOx,nmol/min.100g) determination. NOS activity was measuredin aorta and heart. Protocol II: Aorta, right atria and left ventricle(Ventr)from SHR were removed for determination of NOS catalyticactivity(pmol L-[U14C]-citrulline/g tissue.min) after addition of:ANP(1μM), cANP(4-23)(NPR-C agonist,1μM)or aminoguanidine(AG,iNOSinhibitor,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 SHRAorta 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 washigher than WKY, and ANP treatment increased NOS activity in bothgroups.Protocol II: Results are expressed as percentage of decrease orincrease respect to the NOS basal activity.*p<0.01 vs WKY sametreatment,#p<0.01 vs ANP.AG WKY AG SHR ANP WKY ANP SHR cANP WKY cANP SHRAorta -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 anincreased NOx excretion. In addition, ANP induced an increase of NOS activity in heartand 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 decresewas higher in SHR than WKY, in all tissues, suggesting a higher basal iNOS activity inSHR. ANP and the NPR-C specific agonist provoked similar increases in atrial NOSactivity, indicating that, in atria, ANP would only interact with NPR-C to stimulateNOS activity. In aorta and ventricle, NOS activation via ANP would involve, not onlythe interaction with NPR-C, but also NPR-A and/or in SHR. NOS activation induced byANP via NPR-C would not appear to be altered in this model of hypertension.