| Endothelin A antagonist LU-135252 and trandolapril in the treatment of the Cohen-Rosenthal diabetic hypertensive rat. | |
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MedLine Citation:
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PMID: 16036489 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: Hypertension and non-insulin-dependent diabetes mellitus (NIDDM) often occur simultaneously and the combination requires vigorous control of hypertension. This can generally be achieved by a combination of antihypertensive drugs. The present study examines the antihypertensive and possible hypoglycemic effects of combined therapy with endothelin A (ETA) receptor antagonist LU-135252 and angiotensin-converting enzyme (ACE) inhibitor trandolapril in male Cohen-Rosenthal Diabetic Hypertensive (CRDH) rats. METHODS: Rats were divided into four groups as follows: group I served as control; group II--LU-135252 30 mg/kg/day; group III--trandolapril 0.1 mg/kg/day and group IV--both LU-135252 30 mg/kg/day and trandolapril 0.1 mg/kg/day. Systolic blood pressure (SBP) and plasma glucose levels were evaluated at the beginning of the experiment and after 2, 4 and 6 weeks. RESULTS:SBP decreased significantly in all treated groups after 2, 4 and 6 weeks of treatment compared to baseline. Maximum decrease was in group IV (combination) from 174.8+/-3.7 to 136.1+/-2.4 mmHg (22%) (p<0.0001); in group III (trandolapril) from 165.8+/-2.7 to 137.5+/-2.9 mmHg (17%) (p=0.0002); and in group II (LU-135252) and from 169.1+/-3.1 to 147.8+/-2.5 mmHg (12%) (p=0.0004). Glucose levels in plasma decreased significantly after 6 weeks of treatment. Maximum decrease was in group IV: from 501.0+/-42.8 to 178.6+/-7.3 mg/dl (62%) (p<0.0001); in group III from 428.2+/-47.7 to 146.8+/-5.6 mg/dl (63%) (p<0.0001); and in group II from 491.2+/-39.3 to 272.2+/-28.3 mg/dl (42%) (p=0.0002). CONCLUSION: The SBP decrease was additive when both drugs were given together. Thus, combination of ETA antagonist and ACE inhibitor appears to offer a rational fixed-dose antihypertensive therapy, which is superior to that of either drug alone. The decrease in glucose level, which was the least impressive while on LU-135252 alone, was more prominent during combination after 2 weeks, although without further decrease. |
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Authors:
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Cipy Hofman; Efraim Gabai; Edna Peleg; Klaus Munter; Talma Rosenthal |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Blood pressure Volume: 14 ISSN: 0803-7051 ISO Abbreviation: Blood Press. Publication Date: 2005 |
Date Detail:
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Created Date: 2005-07-22 Completed Date: 2005-08-12 Revised Date: 2010-03-24 |
Medline Journal Info:
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Nlm Unique ID: 9301454 Medline TA: Blood Press Country: Norway |
Other Details:
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Languages: eng Pagination: 114-9 Citation Subset: IM |
Affiliation:
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The Hypertension Unit, Sackler Faculty of Medecine, Tel Aviv University, Tel Aviv, Israel. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Angiotensin-Converting Enzyme Inhibitors
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therapeutic use* Animals Antihypertensive Agents / therapeutic use* Blood Glucose / metabolism Blood Pressure / drug effects Diabetes Complications / drug therapy*, genetics* Drug Combinations Hypertension / drug therapy*, genetics* Indoles / therapeutic use* Male Phenylpropionates / therapeutic use* Pyrimidines / therapeutic use* Rats Rats, Inbred SHR Receptor, Endothelin A / antagonists & inhibitors* Sucrose / pharmacology |
| Chemical | |
Reg. No./Substance:
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0/Angiotensin-Converting Enzyme Inhibitors; 0/Antihypertensive Agents; 0/Blood Glucose; 0/Drug Combinations; 0/Indoles; 0/LU 135252; 0/Phenylpropionates; 0/Pyrimidines; 0/Receptor, Endothelin A; 57-50-1/Sucrose; 87679-37-6/trandolapril |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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