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American Journal of Hypertension
Ezra-Nimni, O., Chorley Inst. for Hypertension Res., Chaim Sheba Medical Center, Tel Hashomer, Israel
Ezra, D., Chorley Inst. for Hypertension Res., Chaim Sheba Medical Center, Tel Hashomer, Israel
Peleg, E., Chorley Inst. for Hypertension Res., Chaim Sheba Medical Center, Tel Hashomer, Israel
Munter, K., Knoll AG, Ludwigshaphen, Germany
Rosenthal, T., Chorley Inst. for Hypertension Res., Chaim Sheba Medical Center, Tel Hashomer, Israel, Chorley Hypertension Institute, Chaim Sheba Medical Center, Tel Hashomer 52621, Israel
Background: In view of the demonstrated interaction between endothelin and the renin-angiotensin system, the antihypertensive effect of combined therapy with an endothelin antagonist LU-135252 and the angiotensin converting enzyme inhibitor trandolapril, was studied in fructose-induced hypertensive, hyperinsulinemic, hypertriglyceridemic male Sprague-Dawley rats. Methods: Forty animals were fed a fructose-enriched diet (Tekled, Harlan) for 5 weeks, as follows: group A, fructose only; group B, trandolapril 0.1 mg/kg/day added during the last 2 weeks; group C, LU-135252 100 mg/kg/day added during the last 2 weeks; group D, both trandolapril and LU-135252 added the last 2 weeks. Systolic blood pressure (BP) was measured weekly in conscious rats by the indirect tail-cuff method. Blood samples from a retro-orbital sinus puncture were taken at the beginning of the experiment and after 3 and 5 weeks and examined for insulin and triglyceride concentrations. Results: Systolic BP decreased in group B (trandolapril) from 148.8 ± 9.8 at 3 weeks to 138.3 ± 8.7 mm Hg after 5 weeks; in group C (endothelin antagonist) from 155.1 ± 5.5 to 142.5 ± 10.6 mm Hg; and in group D (combination) from 154.6 ± 10.9 to 121.2 ± 8.9 mm Hg. Triglyceride levels decreased only in the combined trandolapril/endothelin antagonist group from 167.6 ± 55.3 in the third week to 134.9 ± 53.7 mg/dL after 5 weeks. Insulin levels decreased only on combination therapy from 7.4 ± 3.6 to 5.3 ± 3.8 ng/mL during the same period. The BP decrease was additive compared with the respective individual substances. Conclusions: The trandolapril/endothelin antagonist combination appears to offer a rational antihypertensive combination that is superior to that of either drug alone. This finding applies to the specific rat model studied in which BP, insulin, and triglycerides were increased by fructose diet. © 2003 American Journal of Hypertension, Ltd.
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הספר "אוצר וולקני"
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תנאי שימוש
Trandolapril and endothelin antagonist LU-135252 in the treatment of the fructose-induced hypertensive, hyperinsulinemic, hypertriglyceridemic rat
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Ezra-Nimni, O., Chorley Inst. for Hypertension Res., Chaim Sheba Medical Center, Tel Hashomer, Israel
Ezra, D., Chorley Inst. for Hypertension Res., Chaim Sheba Medical Center, Tel Hashomer, Israel
Peleg, E., Chorley Inst. for Hypertension Res., Chaim Sheba Medical Center, Tel Hashomer, Israel
Munter, K., Knoll AG, Ludwigshaphen, Germany
Rosenthal, T., Chorley Inst. for Hypertension Res., Chaim Sheba Medical Center, Tel Hashomer, Israel, Chorley Hypertension Institute, Chaim Sheba Medical Center, Tel Hashomer 52621, Israel
Trandolapril and endothelin antagonist LU-135252 in the treatment of the fructose-induced hypertensive, hyperinsulinemic, hypertriglyceridemic rat
Background: In view of the demonstrated interaction between endothelin and the renin-angiotensin system, the antihypertensive effect of combined therapy with an endothelin antagonist LU-135252 and the angiotensin converting enzyme inhibitor trandolapril, was studied in fructose-induced hypertensive, hyperinsulinemic, hypertriglyceridemic male Sprague-Dawley rats. Methods: Forty animals were fed a fructose-enriched diet (Tekled, Harlan) for 5 weeks, as follows: group A, fructose only; group B, trandolapril 0.1 mg/kg/day added during the last 2 weeks; group C, LU-135252 100 mg/kg/day added during the last 2 weeks; group D, both trandolapril and LU-135252 added the last 2 weeks. Systolic blood pressure (BP) was measured weekly in conscious rats by the indirect tail-cuff method. Blood samples from a retro-orbital sinus puncture were taken at the beginning of the experiment and after 3 and 5 weeks and examined for insulin and triglyceride concentrations. Results: Systolic BP decreased in group B (trandolapril) from 148.8 ± 9.8 at 3 weeks to 138.3 ± 8.7 mm Hg after 5 weeks; in group C (endothelin antagonist) from 155.1 ± 5.5 to 142.5 ± 10.6 mm Hg; and in group D (combination) from 154.6 ± 10.9 to 121.2 ± 8.9 mm Hg. Triglyceride levels decreased only in the combined trandolapril/endothelin antagonist group from 167.6 ± 55.3 in the third week to 134.9 ± 53.7 mg/dL after 5 weeks. Insulin levels decreased only on combination therapy from 7.4 ± 3.6 to 5.3 ± 3.8 ng/mL during the same period. The BP decrease was additive compared with the respective individual substances. Conclusions: The trandolapril/endothelin antagonist combination appears to offer a rational antihypertensive combination that is superior to that of either drug alone. This finding applies to the specific rat model studied in which BP, insulin, and triglycerides were increased by fructose diet. © 2003 American Journal of Hypertension, Ltd.
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