Role of angiotensin II AT(1) and AT(2) subtype receptors in the regulationof atrial natriuretic peptide expression in salt-restricted rats

Previous studies have suggested that angiotensin II modulates ANP secretion and this action appears to be largely independent from its hemodynamic eff ects. In order to explore the contribution of angiotensin II AT(1) (AT(1)r) and AT(2) (AT(2)r) receptor subtypes in the regulation of cardiac ANP, we studied the effects of selective antagonists of these receptors on ANP mRNA levels in the cardiac chambers of salt-restricted rats. Thirty-one Sprague -Dawley rats (12 weeks-old) weighing 250-350 g were studied during a low sa lt regimen and randomly assigned to the following treatment groups: AT(1)r- blockade (losartan) (10 mg/kg/day) (n = 18), AT(2)r-blockade (PD123319) (50 mu g/kg/min) (n = 6). Control (salt-restriction) (n = 7). Treatments were maintained for 7 days; subsequently, 12 rats from the AT(1)r-blockade group were subdivided in to two groups: AT(1)r/AT(2)r-blockade (losartan +PD1233 19) (n = 6) and AT(1)r-blockade/vehicle (losartan+vehible) (n = 6), and tre ated for 7 additional days. Systolic blood pressure was significantly reduc ed by AT(1)r-blockade (p < 0.001), while it was not affected by AT(2)r-bloc kade. Concomitant treatment with both antagonists (AT(1)r/AT(2)r-blockade) restored blood pressure values to baseline (p < 0.001 vs. AT(1)r-blockade, p = n.s. vs Control). Atrial ANP mRNA was reduced by AT(1)r-blockade (- 42 %, p < 0.05) and did not change during AT(1)r-blockade alone. On the contra ry, concomitant treatment with both antagonists resulted in a further signi ficant inhibition of ANP expression (- 65 % and - 36 % vs Control and AT(1) r-blockade, nspectively, both p < 0.05). ANP expression in ventricles was n ot affected by any of these treatments. Our results demonstrate that angiotensin II tonically modulates cardiac ANP expression in our experimental model. In particular, angiotensin II recept or subtypes AT(1)r and AT(2)r regulate atrial ANP mRNA levels through a syn ergic action and independently from blood pressure changes.