Effects of losartan on pressure overload-induced cardiac gene expression profiling in rats.

Abstract

1. In the present study, the effects of losartan on myocardial gene expression changes following cardiac hypertrophy were investigated. 2. Male Wistar rats were randomized to receive 5 or 30 mg/kg per day losartan (i.p.) 1 day after suprarenal abdominal aortic constriction. Two weeks later, cardiac morphology and function were recorded with echocardiography and mean arterial central pressure was measured using carotid catheters. Myocardial gene expression was assessed with cDNA microarrays. 3. The ratios of left ventricular weights to bodyweights, the posterior thickness of the left ventricle and mean arterial central pressure were significantly increased by aortic constriction and attenuated by losartan in a dose-related manner. Genes in different functional categories were regulated in pressure overload-induced cardiac hypertrophy and the majority of changes in gene expression were inhibited by losartan in a dose-dependent manner. 4. However, there were still some genes that were unaffected by losartan, even at a higher dose. In contrast, losartan, especially at a lower dose, was able to induce changes in the expression of several additional genes that were unregulated in simple aortic constriction. 5. In conclusion, losartan is able to inhibit pressure overload-induced cardiac hypertrophy, as well as the majority of pressure overload-related changes in gene expression. The genes that remained unaffected or those that were additionally induced by losartan are likely to be new targets for investigation or therapy.