Paola De Paolis - Academia.edu (original) (raw)
Papers by Paola De Paolis
Basic Research in Cardiology, 2000
Previous studies have suggested that angiotensin II modulates ANP secretion and this action appea... more Previous studies have suggested that angiotensin II modulates ANP secretion and this action appears to be largely independent from its hemodynamic effects. 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 salt 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 µg/kg/min) (n = 6), Control (salt-restriction) (n = 7). Treatments were maintained for 7 days; subsequently, 12 rats from the AT 1 rblockade group were subdivided in to two groups: AT 1 r/AT 2 r-blockade (losartan +PD123319) (n = 6) and AT 1 r-blockade/vehicle (losartan+vehible) (n = 6), and treated for 7 additional days. Systolic blood pressure was significantly reduced by AT 1 r-blockade (p < 0.001), while it was not affected by AT 2 r-blockade. 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 2 r-blockade alone. On the contrary, concomitant treatment with both antagonists resulted in a further significant inhibition of ANP expression (-65 % and-36 % vs Control and AT 1 r-blockade, respectively, both p < 0.05). ANP expression in ventricles was not 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 receptor subtypes AT 1 r and AT 2 r regulate atrial ANP mRNA levels through a synergic action and independently from blood pressure changes.
American journal of …, 2005
Vasoconstrictive, proliferative and oxidative effects of angiotensin II (Ang II) are mediated by ... more Vasoconstrictive, proliferative and oxidative effects of angiotensin II (Ang II) are mediated by Ang II type 1 (AT 1 ) receptors. The effects of Ang II via the Ang II type 2 (AT 2 ) receptor subtype (AT 2 R) are less well defined. Growing evidence shows the existence of cross-talk ...
The renin-angiotensin-aldosterone system (RAAS) plays an important role in the pathogenesis of hy... more The renin-angiotensin-aldosterone system (RAAS) plays an important role in the pathogenesis of hypertension as well as cardiovascular diseases and chronic kidney diseases. Among the most frequently studied RAAS gene polymorphisms are the angiotensin-converting enzyme insertion/deletion (I/D), angiotensinogen M235T and angiotensin II receptor type 1 A1166C polymorphisms. A significant correlation was found between the I/D polymorphism and cardiovascular morbidity and mortality rates. However, there was no significant correlation between I/D, M235T, A1166C polymorphism and arterial hypertension. The role of I/D polymorphism in the development and progression of chronic kidney disease is also non-conclusive. However, DD genotype has been identified as relevant for loss of renal function both in patients with IgA nephropathy and in patients of Asian origin with diabetic nephropathy. The relationship between RAAS gene polymorphism and transplanted kidney function has not been confirmed in large prospective and retrospective studies. there is no clear opinion concerning the influence of RAAS genotypes on the prevalence of post-transplant hypertension or erythrocytosis. Although a role of RAAS gene polymorphism in kidney function deterioration could not be ruled out, it is more likely that a variety of genetic and environmental factors influence the progression of chronic kidney diseases.
Basic Research in Cardiology, 2000
Previous studies have suggested that angiotensin II modulates ANP secretion and this action appea... more Previous studies have suggested that angiotensin II modulates ANP secretion and this action appears to be largely independent from its hemodynamic effects. 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 salt 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 µg/kg/min) (n = 6), Control (salt-restriction) (n = 7). Treatments were maintained for 7 days; subsequently, 12 rats from the AT 1 rblockade group were subdivided in to two groups: AT 1 r/AT 2 r-blockade (losartan +PD123319) (n = 6) and AT 1 r-blockade/vehicle (losartan+vehible) (n = 6), and treated for 7 additional days. Systolic blood pressure was significantly reduced by AT 1 r-blockade (p < 0.001), while it was not affected by AT 2 r-blockade. 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 2 r-blockade alone. On the contrary, concomitant treatment with both antagonists resulted in a further significant inhibition of ANP expression (-65 % and-36 % vs Control and AT 1 r-blockade, respectively, both p < 0.05). ANP expression in ventricles was not 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 receptor subtypes AT 1 r and AT 2 r regulate atrial ANP mRNA levels through a synergic action and independently from blood pressure changes.
American journal of …, 2005
Vasoconstrictive, proliferative and oxidative effects of angiotensin II (Ang II) are mediated by ... more Vasoconstrictive, proliferative and oxidative effects of angiotensin II (Ang II) are mediated by Ang II type 1 (AT 1 ) receptors. The effects of Ang II via the Ang II type 2 (AT 2 ) receptor subtype (AT 2 R) are less well defined. Growing evidence shows the existence of cross-talk ...
The renin-angiotensin-aldosterone system (RAAS) plays an important role in the pathogenesis of hy... more The renin-angiotensin-aldosterone system (RAAS) plays an important role in the pathogenesis of hypertension as well as cardiovascular diseases and chronic kidney diseases. Among the most frequently studied RAAS gene polymorphisms are the angiotensin-converting enzyme insertion/deletion (I/D), angiotensinogen M235T and angiotensin II receptor type 1 A1166C polymorphisms. A significant correlation was found between the I/D polymorphism and cardiovascular morbidity and mortality rates. However, there was no significant correlation between I/D, M235T, A1166C polymorphism and arterial hypertension. The role of I/D polymorphism in the development and progression of chronic kidney disease is also non-conclusive. However, DD genotype has been identified as relevant for loss of renal function both in patients with IgA nephropathy and in patients of Asian origin with diabetic nephropathy. The relationship between RAAS gene polymorphism and transplanted kidney function has not been confirmed in large prospective and retrospective studies. there is no clear opinion concerning the influence of RAAS genotypes on the prevalence of post-transplant hypertension or erythrocytosis. Although a role of RAAS gene polymorphism in kidney function deterioration could not be ruled out, it is more likely that a variety of genetic and environmental factors influence the progression of chronic kidney diseases.