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(Circulation. 2000;102:2210.)
© 2000 American Heart Association, Inc.

Clinical Investigation and Reports

Angiotensin II Receptor Subtypes in the Skeletal Muscle Vasculature of Patients With Severe Congestive Heart Failure

Slawomir L. Malendowicz, MD; Pierre V. Ennezat, MD; Marco Testa, MD, PhD; Laura Murray, BSc; Edmund H. Sonnenblick, MD; Todd Evans, PhD; Thierry H. LeJemtel, MD

From the Department of Medicine, Division of Cardiology (S.L.M,, P.B.E., M.T., E.H.S.), and the Department of Developmental and Molecular Biology (S.L.M., P.V.E., L.M., T.E.), the Albert Einstein College of Medicine, Bronx, NY.

Correspondence to Thierry H. Le Jemtel, MD, Albert Einstein College of Medicine, 1300 Morris Park Ave, Forch, G-42, Bronx, New York 10461. E-mail lejemtel{at}aecom.yu.edu

Background—Vascular remodeling occurs in the skeletal muscle of patients with severe congestive heart failure (CHF); this remodeling is mediated in part by increased activity of the renin-angiotensin system. Animal models suggest that in the vasculature, angiotensin II receptor type 2 (AT2-R) expression may be upregulated in pathological states associated with vascular remodeling. The therapeutic effects of an AT1-R antagonist may, therefore, be in part due to increased plasma angiotensin II levels, which stimulate AT2-R. However, whether AT2-R is expressed in the skeletal muscle vasculature of patients with severe CHF is unknown.

Methods and Results—The steady-state transcript levels of the AT1-R and AT2-R genes were analyzed by reverse transcription–polymerase chain reaction in RNA samples prepared from the skeletal muscle of 12 patients with severe CHF (O₂<10 mL · kg^-1 · min^-1) and 5 age-matched healthy subjects who underwent vastus lateralis biopsies. Human fetal skeletal muscle RNA served as a positive control for the expression of AT1-R and AT2-R gene transcripts. Transcripts from the AT1-R gene were detected readily in all samples. In contrast, transcripts from the AT2-R gene were only detected in fetal skeletal muscle samples and could not be detected in the skeletal muscle vasculature of healthy subjects or that of CHF patients, who were treated with either angiotensin-converting enzyme inhibitors or AT1-R antagonists.

Conclusions—The AT2-R gene is not expressed in the skeletal muscle of patients with CHF. In the absence of detectable AT2-R gene transcripts, the AT2-R pathway is unlikely to contribute to the effects of AT1-R antagonists on the skeletal muscle vasculature in patients with severe CHF.

Key Words: angiotensins • receptors • heart failure • muscle, skeletal

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