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Different effects of antihypertensive agents on cardiac and vascular hypertrophy in the transgenic rat line TGR(mRen2)27.

TitleDifferent effects of antihypertensive agents on cardiac and vascular hypertrophy in the transgenic rat line TGR(mRen2)27.
Publication TypeJournal Article
Year of Publication1999
AuthorsBrosnan MJ, Devlin AM, Clark JS, Mullins JJ, Dominiczak AF
JournalAm J Hypertens
Date Published1999 Jul
KeywordsAngiotensin-Converting Enzyme Inhibitors, Animals, Animals, Genetically Modified, Antihypertensive Agents, Aorta, Thoracic, Aortic Diseases, Cardiomegaly, Cell Cycle, DNA, Drug Therapy, Combination, Female, Flow Cytometry, Follow-Up Studies, Heart Ventricles, Hydralazine, Hydrochlorothiazide, Hypertension, Hypertrophy, Indoles, Male, Muscle, Smooth, Vascular, Perindopril, Rats, Rats, Sprague-Dawley, Renin-Angiotensin System, Transgenes

The hypertensive transgenic rat model TGR(mRen2)27 has been used to investigate the development of cardiac and vascular hypertrophy in response to two different drug regimes. Cardiac hypertrophy was shown to be related to age and gender with the copy number of mouse renin transgenes having an additive effect. A similar observation was noted for hypertrophy in the vasculature, which was assessed using flow cytometry cell cycle DNA analysis of aortic vascular smooth muscle cells. Chronic treatment from weaning with equihypotensive doses of perindopril (2 mg/kg/day) or hydralazine and hydrochlorothiazide (4 mg/day of each) prevented the development of cardiac hypertrophy. Perindopril treatment also effectively prevented the development of vascular hypertrophy; however, treatment with hydralazine and hydrochlorothiazide was not as effective despite equivalent blood pressure reduction. These studies have demonstrated the presence of marked vascular and cardiac hypertrophy in the hypertensive transgenic TGR(mRen2)27 model of hypertension. Furthermore, these results provide new evidence to support the role of a locally activated renin angiotensin system in the blood vessel wall, which is involved in the pathogenesis of vascular hypertrophy in this transgenic rat model.

Alternate JournalAm. J. Hypertens.
PubMed ID10411370