Telmisartan, an
angiotensin receptor blocker, may have unique benefits as it possesses partial
peroxisome proliferator-activated receptor (
PPAR)-γ agonist activity in addition to
antihypertensive effects. In this study, we test whether treatment with
telmisartan ameliorates
cardiovascular abnormalities to a greater extent than
olmesartan, which has little
PPAR-γ activity. The hypertensive rodent model of tissue renin-angiotensin system activation, transgenic (mRen2)27 (Ren2) rats and their littermate Sprague-Dawley controls were used. Rats were treated with
telmisartan (2 mg · kg(-1) · day(-1)),
olmesartan (2.5 mg · kg(-1) · day(-1)), or vehicle via
drinking water for 3 wk; these doses achieved similar blood pressure control, as measured by telemetry. Ren2 rats displayed impaired diastolic and systolic function using left ventricular (LV) pressure-volume (P-V) analysis. Load-independent diastolic indexes, including the time constant of isovolumic relaxation and the slope of the end-diastolic P-V relationship, as well as systolic indexes, including preload recruitable
stroke work, the dP/dt(max)-end-diastolic volume (EDV) relationship, and the P-V area-EDV relationship, were elevated in Ren2 rats compared with Sprague-Dawley controls (P < 0.05). The Ren2 myocardium exhibited parallel increases in the
oxidant markers
NADPH oxidase and
3-nitrotyrosine. The increase in the prohypertrophic
protein Jak2 in Ren2 rats was associated with cardiac structural abnormalities using light microscopic and ultrastructural analysis, which included interstitial
fibrosis, cardiomyocyte and LV
hypertrophy, and mitochondrial derangements. Both
angiotensin receptor blockers attenuate these abnormalities to a similar extent. Our data suggest that the beneficial effect of
telmisartan and
olmesartan on cardiac structure and function may be predominantly pressor-related or
angiotensin type 1 receptor dependent in this model of renin-angiotensin system activation.