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

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

Research output: Contribution to journalArticle

17 Scopus citations

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/dtmax-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.

Original languageEnglish (US)
Pages (from-to)H181-H190
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume300
Issue number1
DOIs
StatePublished - Jan 1 2011

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Keywords

  • AMP-activated protein kinase
  • Janus-activated kinase 2
  • Left ventricular hypertrophy
  • Oxidative stress
  • Peroxisome proliferator-activated receptor-γ

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

DeMarco, V. G., Johnson, M. S., Habibi, J., Pulakat, L., Gul, R., Hayden, M. R., Tilmon, R. D., Dellsperger, K. C., Winer, N., Whaley-Connell, A. T., & Sowers, J. R. (2011). Comparative analysis of telmisartan and olmesartan on cardiac function in the transgenic (mRen2)27 rat. American Journal of Physiology - Heart and Circulatory Physiology, 300(1), H181-H190. https://doi.org/10.1152/ajpheart.00883.2010