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Effect of ETA receptor antagonist and aldosterone antagonist on blood pressure and vascular remodeling in aldosterone-infused rats
134A
POSTERS: Endothelial Factors
nmol/mg (P⬍0.01) with INS alone. BK⫹INS increased NOx to 18.9 nmol/mg (P⬍0.01). Also, INS from 0.01 to 10 nmol/L increased BKinduced NOx generation in HCAEC in a dose-related manner. These results show that INS enhances the NO response of VEC to BK, similar to the effect of INS on the BK-induced iCa2⫹ response. Thus, INS may enhance BK’s NO production, in part, through a Ca-dependent mechanism in both BAEC and HCAEC. Key Words: Endothelial Cell, Nitric Oxide, Insulin
P-286 EFFECT OF ETA RECEPTOR ANTAGONIST AND ALDOSTERONE ANTAGONIST ON BLOOD PRESSURE AND VASCULAR REMODELING IN ALDOSTERONE-INFUSED RATS Qian Pu, Mario F. Neves, Agostino Virdis, Ernesto L. Schiffrin. Experimental Hypertension, Clinical Research Institute of Montreal, Montreal, Quebec, Canada. Endothelin and aldosterone play an important role in vascular remodeling in hypertension. Our previous results demonstrate that endothelin-1 is involved in vascular remodeling in aldosterone and salt-induced hyper-
AJH–April 2002–VOL. 15, NO. 4, PART 2
tension. The aim of this study was to evaluate the effects of the ETa receptor antagonist BMS 182874 and of the aldosterone antagonist spironolactone on blood pressure and vascular remodeling in aldosteroneinfused rats. Male Sprague-Dawley rats were infused with aldosterone (0.75g/h) subcutaneously. BMS 182874 (40 mg/kg/d) and spironolactone (25mg/kg/d) were given with food for 6 weeks. Systolic BP was monitored by the tail-cuff method and effects on mesenteric resistance arteries were studied on a pressurized myograph. Aldosterone infusion increased BP (to 149 ⫾ 5.8 vs 115 ⫾ 1.2 mmHg in control, p⬍0.01) and media thickness of small arteries (to 17.7 ⫾ 0.9 vs 13.6 ⫾ 0.8 m in control, p⬍0.05). BMS 182874 and spironolactone treatment decreased systolic BP (118 ⫾ 5.1 and 120 ⫾ 3.6 mmHg, respectively, p⬍0.01 vs untreated) and normalized media thickness of resistance arteries (14.2 ⫾ 0.7 and 14.4 ⫾ 0.6 m, respectively, P⬍0.05 vs untreated) of aldosterone-infused rats. The elevation in BP and the vascular remodeling of small arteries in aldosterone-infused rats in the absence of salt loading may be mediated by ETa receptor. Blockade of the endothelin system may exert beneficial effects on vascular remodeling in aldosteroneinduced hypertension. Key Words: Endothelin, Aldosterone, Vascular Remodeling
POSTERS: Endothelial Factors
nmol/mg (P⬍0.01) with INS alone. BK⫹INS increased NOx to 18.9 nmol/mg (P⬍0.01). Also, INS from 0.01 to 10 nmol/L increased BKinduced NOx generation in HCAEC in a dose-related manner. These results show that INS enhances the NO response of VEC to BK, similar to the effect of INS on the BK-induced iCa2⫹ response. Thus, INS may enhance BK’s NO production, in part, through a Ca-dependent mechanism in both BAEC and HCAEC. Key Words: Endothelial Cell, Nitric Oxide, Insulin
P-286 EFFECT OF ETA RECEPTOR ANTAGONIST AND ALDOSTERONE ANTAGONIST ON BLOOD PRESSURE AND VASCULAR REMODELING IN ALDOSTERONE-INFUSED RATS Qian Pu, Mario F. Neves, Agostino Virdis, Ernesto L. Schiffrin. Experimental Hypertension, Clinical Research Institute of Montreal, Montreal, Quebec, Canada. Endothelin and aldosterone play an important role in vascular remodeling in hypertension. Our previous results demonstrate that endothelin-1 is involved in vascular remodeling in aldosterone and salt-induced hyper-
AJH–April 2002–VOL. 15, NO. 4, PART 2
tension. The aim of this study was to evaluate the effects of the ETa receptor antagonist BMS 182874 and of the aldosterone antagonist spironolactone on blood pressure and vascular remodeling in aldosteroneinfused rats. Male Sprague-Dawley rats were infused with aldosterone (0.75g/h) subcutaneously. BMS 182874 (40 mg/kg/d) and spironolactone (25mg/kg/d) were given with food for 6 weeks. Systolic BP was monitored by the tail-cuff method and effects on mesenteric resistance arteries were studied on a pressurized myograph. Aldosterone infusion increased BP (to 149 ⫾ 5.8 vs 115 ⫾ 1.2 mmHg in control, p⬍0.01) and media thickness of small arteries (to 17.7 ⫾ 0.9 vs 13.6 ⫾ 0.8 m in control, p⬍0.05). BMS 182874 and spironolactone treatment decreased systolic BP (118 ⫾ 5.1 and 120 ⫾ 3.6 mmHg, respectively, p⬍0.01 vs untreated) and normalized media thickness of resistance arteries (14.2 ⫾ 0.7 and 14.4 ⫾ 0.6 m, respectively, P⬍0.05 vs untreated) of aldosterone-infused rats. The elevation in BP and the vascular remodeling of small arteries in aldosterone-infused rats in the absence of salt loading may be mediated by ETa receptor. Blockade of the endothelin system may exert beneficial effects on vascular remodeling in aldosteroneinduced hypertension. Key Words: Endothelin, Aldosterone, Vascular Remodeling