Influence of atrial natriuretic peptide treatment on cardiovascular and renal nitric oxide system in spontaneously hypertensive rats

COSTA MARIA DE LOS ANGELES; RODRIGUEZ IERACE DANIELA; ELESGARAY ROSANA; VISINTINI JAIME MARIA FLORENCIA; CANIFFI CAROLINA; BALASZCZUK ANA MARÍA; ARRANZ CRISTINA

Buenos Aires, Argentina

Congreso; World Congress of Cardiology 2008; 2008

World Heart Federation

Introduction: We have previously demonstrated that nitric oxide (NO) system mediates atrial natriuretic peptide (ANP) hypotensive, natriuretic and diuretic effects in normotensive rats. We also showed that ANP would stimulate NO synthase (NOS) activity interacting with natriuretic peptides receptors NPR-A/B, increasing cGMP, and/or NPR-C, coupled via G protein, which activates Ca2+-calmodulin dependent NOS. Objective: The aim of the present study was to investigate the effects of chronic ANP infusion on systolic blood pressure (SBP) and cardiovascular and renal NO system in spontaneously hypertensive rats (SHR). Methods: 16-weeks old SHR and normotensive Wistar-Kyoto rats (WKY) were infused subcutaneously (osmotic pumps) with saline (NaCl 0.9%) or ANP (100 ng/hour.rat), during seven days. SBP was recorded and nitrites and nitrates excretion (NOx, metabolic end products of NO) were determined during the experimental time. At the end of this period, the animals were sacrificed by decapitation and NOS activity (using [14C] L-arginine as substrate) were determined in aorta artery (A), right atria (RA), left ventricle (LV) and renal medulla (M) and cortex (C). Results: Chronic infusion of ANP diminished SBP (WKY= -13±3 vs SHR= -25 ± 10 mmHg, ns) and increased NOx (WKY = 41 ± 10 % vs SHR = 23 ± 4 %, p<0.01) in both groups. ANP increased NOS activity in all studied tissues in both groups but the enzyme stimulation was more marked in WKY than SHR. (A: WKY= 51 ± 4 % vs SHR = 40 ± 3 % *; RA: WKY = 46 ± 4 % vs SHR = 38 ± 3 %*; LV: WKY = 41 ± 3 % vs SHR = 30 ± 4 % *; C: WKY = 38 ± 4 % vs SHR = 27 ± 3 % *; M: WKY = =30 ± 3 % vs SHR = 25 ± 2 % *; * p<0.01) Table: NOS activity (pmol/g tissue.min) induced by saline or ANP in WKY and SHR animals WKY + Saline WKY + ANP SHR + Saline SHR + ANP Aorta artery 205 ± 12 313 ± 15 * 339 ± 16 # 474 ± 18 * Right atria 198 ± 11 289 ± 10 * 321 ± 15 # 444 ± 19 * Left ventricle 212 ± 14 506 ± 26 * 327 ± 16 # 425 ± 20 * Renal cortex 289 ± 15 400 ± 17 * 468 ± 19 # 595 ± 23 * Renal medulla 388 ± 18 506 ± 26 * 594 ± 25 # 742 ± 29 * * p<0.01 vs saline infusion same group, # p<0.01 vs WKY + saline. Conclusions: These results would suggest that up-regulation of cardiovascular and renal NO-system is a compensatory mechanism for the elevation of systolic blood pressure during the development of hypertension in SHR. The chronic treatment with ANP increased the activity of this system associated with a decrease in arterial blood pressure. The impaired response to ANP of cardiovascular and renal NO system in hypertensive animals, would be one of the mechanisms involved in the development and/or the maintenance of the high blood pressure in this model of genetic hypertension.