Comparative analysis of telmisartan and olmesartan on cardiac function in the transgenic (mRen2)27 rat.

Abstract

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.

• Authors: Vincent G DeMarco, Megan S Johnson, Javad Habibi, Lakshmi Pulakat, Rukhsana Gul, Melvin R Hayden, Roger D Tilmon, Kevin C Dellsperger, Nathaniel Winer, Adam T Whaley-Connell, James R Sowers
• Journal: American journal of physiology. Heart and circulatory physiology (Am J Physiol Heart Circ Physiol) Vol. 300 Issue 1 Pg. H181-90 (Jan 2011) ISSN: 1522-1539 [Electronic] United States
• PMID: 21057043 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Angiotensin II Type 1 Receptor Blockers
• Benzimidazoles
• Benzoates
• Imidazoles
• Tetrazoles
• olmesartan
• Janus Kinase 2
• Telmisartan

Topics

• Analysis of Variance
• Angiotensin II Type 1 Receptor Blockers (pharmacology)
• Animals
• Benzimidazoles (pharmacology)
• Benzoates (pharmacology)
• Blood Pressure (drug effects)
• Body Weight (drug effects)
• Heart (drug effects)
• Heart Function Tests
• Hypertrophy, Left Ventricular (metabolism)
• Imidazoles (pharmacology)
• Janus Kinase 2 (metabolism)
• Male
• Myocardium (metabolism)
• Myocytes, Cardiac (drug effects, metabolism)
• Oxidative Stress (drug effects)
• Phosphorylation (drug effects)
• Rats
• Rats, Sprague-Dawley
• Rats, Transgenic
• Renin-Angiotensin System (drug effects)
• Telemetry
• Telmisartan
• Tetrazoles (pharmacology)