Favorable cardiac and aortic remodeling in olmesartan-treated spontaneously hypertensive rats.
Cardiovascular remodeling contributes to the progression of cardiovascular disease. Thus, our aim was to evaluate the action of long-term treatment with olmesartan on cardiac and aortic adverse remodeling and its relationship with blood pressure (BP) and tensile forces acting on the aortic wall. Five-month-old male rats were divided in: WKY group (n = 6), SHR group (n = 6), and SHRs treated with hydralazine 30 mg/kg/day (SHR-H, n = 8) or olmesartan 10 mg/kg/day (SHR-O, n = 8). Medications were administered for 16 weeks. The SHR group showed hypertension (189 +/- 4 mmHg), cardiomyocyte hypertrophy (+107%), interstitial fibrosis (5.7% vs 1.9% in WKY), and reduced intramyocardial vascularization (9.1% vs 22.8% in WKY). In aorta, the SHRs showed outward hypertrophic remodeling, increased elastic fibers content (+36%), and increased circumferential wall tension (CWT, 2.79 x 10(4) dyne/cm) and tensile stress (TS, 261.4 x 10(4) dyne/cm(2)). Hydralazine and olmesartan decreased BP (-45% approximately) and likewise CWT and TS (-45% and -35% approximately). Both medications prevented left ventricle remodeling, but olmesartan improved cardiomyocyte hypertrophy better than hydralazine. Hydralazine did not alter media hypertrophy, but it enlarged lumen diameter and increased elastic fibers. It is unlikely that olmesartan prevented all aortic alterations. Taken together, long-term control of BP alone is not sufficient to prevent aortic remodeling due to hypertension, but in myocardium it seems to be enough, except for cardiomyocyte hypertrophy. The differential action of olmesartan suggests that it is essential to block growth stimulation by angiotensin II in cardiomyocytes and vascular smooth muscle cells in order to better prevent cardiovascular adverse remodeling due to arterial hypertension.
Fernandes-Santos
Caroline
C
Laboratory of Morphometry and Cardiovascular Morphology, Biomedical Center, Institute of Biology, State University of Rio de Janeiro, Av. 28 de Setembro 87 fds, 20551-030 Rio de Janeiro, RJ, Brazil.
de Souza Mendonça
Leonardo
L
Mandarim-de-Lacerda
Carlos Alberto
CA
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D006830:Hydralazine / Q000494:pharmacology; D006973:Hypertension / Q000188:drug therapy*; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects; D051381:Rats; D013777:Tetrazoles / Q000494:pharmacology*; D020257:Ventricular Remodeling / Q000187:drug effects*
D000959:Antihypertensive Agents; D007093:Imidazoles; D013777:Tetrazoles; D006830:Hydralazine; C437965:olmesartan