Papers by Srinivasan Rajagopalan
Circulation, 2002
Background-Aldosterone has been implicated in the effects of angiotensin II in the vasculature. W... more Background-Aldosterone has been implicated in the effects of angiotensin II in the vasculature. We hypothesized that there is local expression of the mineralocorticoid receptor (MR) in the vasculature and that the use of a selective aldosterone receptor antagonist (SARA) improves endothelial function in early atherosclerosis. Methods and Results-New Zealand rabbits were placed on normal chow or 1% cholesterol diets, randomized to placebo or SARA (eplerenone, 50 mg/kg twice daily), and killed at the end of 6 weeks for various studies. In the hyperlipidemic (HL) chow group, there was a 2.3-fold increase in superoxide (O 2 ⅐Ϫ ) generation. SARA normalized O 2 ⅐Ϫ generation in intact aortas and reduced NADH and NADPH oxidase activity to basal levels (0.31Ϯ0.04 and 0.27Ϯ0.02 in HL versus 0.16Ϯ0.05 and 0.07Ϯ0.02 in HL-SARA, respectively; PϽ0.01 by ANOVA). This was associated with improvements in peak relaxations to the endothelial-dependent agonist acetylcholine (82Ϯ6% in HL-SARA versus 61Ϯ4 in HL; PϽ0.01 by ANOVA; ED 50 6.8ϫ10 Ϫ8 mol/L in HL-SARA and 1.2ϫ10 Ϫ7 mol/L in HL; PϭNS) to near-normal levels. Vessels from the HL group demonstrated hyperreactivity to angiotensin II that could not be corrected with SARA. Plasma aldosterone levels by radioimmunoassay demonstrated a 4-to 5-fold increase in response to SARA but no differences with lipid feeding. Real-time reverse transcriptase-polymerase chain reaction studies revealed expression of MR in the aorta of HL rabbits and those of controls.
Circulation, 2002
Background-Aldosterone has been implicated in the effects of angiotensin II in the vasculature. W... more Background-Aldosterone has been implicated in the effects of angiotensin II in the vasculature. We hypothesized that there is local expression of the mineralocorticoid receptor (MR) in the vasculature and that the use of a selective aldosterone receptor antagonist (SARA) improves endothelial function in early atherosclerosis. Methods and Results-New Zealand rabbits were placed on normal chow or 1% cholesterol diets, randomized to placebo or SARA (eplerenone, 50 mg/kg twice daily), and killed at the end of 6 weeks for various studies. In the hyperlipidemic (HL) chow group, there was a 2.3-fold increase in superoxide (O 2 ⅐Ϫ ) generation. SARA normalized O 2 ⅐Ϫ generation in intact aortas and reduced NADH and NADPH oxidase activity to basal levels (0.31Ϯ0.04 and 0.27Ϯ0.02 in HL versus 0.16Ϯ0.05 and 0.07Ϯ0.02 in HL-SARA, respectively; PϽ0.01 by ANOVA). This was associated with improvements in peak relaxations to the endothelial-dependent agonist acetylcholine (82Ϯ6% in HL-SARA versus 61Ϯ4 in HL; PϽ0.01 by ANOVA; ED 50 6.8ϫ10 Ϫ8 mol/L in HL-SARA and 1.2ϫ10 Ϫ7 mol/L in HL; PϭNS) to near-normal levels. Vessels from the HL group demonstrated hyperreactivity to angiotensin II that could not be corrected with SARA. Plasma aldosterone levels by radioimmunoassay demonstrated a 4-to 5-fold increase in response to SARA but no differences with lipid feeding. Real-time reverse transcriptase-polymerase chain reaction studies revealed expression of MR in the aorta of HL rabbits and those of controls.
Journal of Experimental Medicine, 2005
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Papers by Srinivasan Rajagopalan