Irbesartan prevents myocardial remodeling in experimental thyrotoxic cardiomyopathy.
This study evaluated the effects of irbesartan and propranolol on thyroid hormone (TH)-induced cardiac functional and structural remodeling. A rat model of thyrotoxicosis was established by daily intraperitoneal injections of L-thyroxine (T(4), 100 μg/kg) for 4 weeks.  Forty Sprague-Dawley rats were randomly divided into four groups (n = 10 each): control group, T(4) group (T(4) alone), T(4) plus irbesartan group (T(4)-Irb, 30 mg/kg), and T(4) plus propranolol group (T(4)-Pro, 0.5mg/mL of drinking water).  Cardiac chamber size and functional parameters were measured by echocardiography and cardiomyocyte diameter.  Heart rate (HR) and cardiac fibrosis were determined.  T(4) alone showed significantly increased HR and cardiomyocyte width (25.0 ± 1.77 vs. 18.8 ± 0.84 μm, P < 0.001) with fibrosis, reduced left ventricle (LV) longitudinal strain (S(long); -16.0 ± 6.27 vs. -22.7 ± 5.19 %, P < 0.001) compared with control.  When compared with T(4) alone, T(4)-Irb showed significantly improved LV S(long) (-21.4 ± 1.84 vs. -16.0 ± 6.27 %, P =0.017) and reduced cardiomyocyte width (21.0 ± 1.0 vs. 25.0 ± 1.77 μm, P =0.002) with comparable HR (458.4 ± 24.3 vs. 486.6 ± 30.1 bpm, P = 0.086).  However, T(4)-Pro showed significantly reduced HR with improved LV S(long) without alteration of cardiomyocyte width and fibrosis compared with T(4) alone.  In conclusion, renin-angiotensin system (RAS) blocking by irbesartan could significantly attenuate TH-induced cardiac structural and functional remodeling.  However, HR reduction by propranolol could not alternate structural remodeling, which may implicate the RAS as having an important role in thyrotoxic cardiomyopathy beyond tachycardia.
Department of Internal Medicine, Pusan National University School of Medicine, Busan 602-739, Korea.
Bo Hyun
BH
Kim
Kyoung Im
KI
Cho
Seong Man
SM
Kim
Jee-Yeon
JY
Kim
Bo Gwang
BG
Choi
Ji Hyun
JH
Kang
Yun Kyung
YK
Jeon
Sang Soo
SS
Kim
Seong-Jang
SJ
Kim
Yong Ki
YK
Kim
In Joo
IJ
Kim
D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D000818:Animals; D001713:Biphenyl Compounds / Q000627:therapeutic use*; D009202:Cardiomyopathies / Q000139:chemically induced / Q000473:pathology*; D004452:Echocardiography; D006339:Heart Rate / Q000187:drug effects; D000077405:Irbesartan; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012084:Renin-Angiotensin System / Q000187:drug effects; D013777:Tetrazoles / Q000627:therapeutic use*; D013971:Thyrotoxicosis / Q000473:pathology*; D013974:Thyroxine; D020257:Ventricular Remodeling / Q000187:drug effects*
D047228:Angiotensin II Type 1 Receptor Blockers; D001713:Biphenyl Compounds; D013777:Tetrazoles; D011433:Propranolol; D000077405:Irbesartan; D013974:Thyroxine