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Comparison of the effects of candesartan cilexetil and enalapril maleate on right ventricular myocardial remodeling in dogs with experimentally induced pulmonary stenosis

Tsuyoshi Yamane DVM, PhD1, Yoko Fujii DVM, PhD2, Kensuke Orito DVM, PhD3, Kaori Osamura DVM4, Takao Kanai DVM, PhD5, and Yoshito Wakao DVM, PhD6
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  • 1 Department of Surgery, School of Veterinary Medicine, Azabu University, Kanagawa, 229-8501, Japan
  • | 2 Department of Surgery, School of Veterinary Medicine, Azabu University, Kanagawa, 229-8501, Japan
  • | 3 Department of Surgery Pharmacology, School of Veterinary Medicine, Azabu University, Kanagawa, 229-8501, Japan
  • | 4 Department of Surgery, School of Veterinary Medicine, Azabu University, Kanagawa, 229-8501, Japan
  • | 5 Institute of Laboratory Animals, Tokyo Women's Medical University, Kawada-cho, Shinjuku, Tokyo, 162-8666, Japan
  • | 6 Department of Surgery, School of Veterinary Medicine, Azabu University, Kanagawa, 229-8501, Japan

Abstract

Objective—To compare the effects of candesartan cilexetil and enalapril maleate on right ventricular myocardial remodeling in dogs with experimentally induced pulmonary stenosis.

Animals—24 Beagles.

Procedures—18 dogs underwent pulmonary arterial banding (PAB) to induce right ventricular pressure overload, and 6 healthy dogs underwent sham operations (thoracotomy only [sham-operated group]). Dogs that underwent PAB were allocated to receive 1 of 3 treatments (6 dogs/group): candesartan (1 mg/kg, PO, q 24 h [PABC group]), enalapril (0.5 mg/kg, PO, q 24 h [PABE group]), or no treatment (PABNT group). Administration of treatments was commenced the day prior to surgery; control dogs received no cardiac medications. Sixty days after surgery, right ventricular wall thickness was assessed echocardiographi-cally and plasma renin activity, angiotensin-converting enzyme activity, and angiotensin I and II concentrations were assessed; all dogs were euthanatized, and collagenous fiber area, cardiomyocyte diameter, and tissue angiotensin-converting enzyme and chymase-like activities in the right ventricle were evaluated.

Results—After 60 days of treatment, right ventricular wall thickness, cardiomyocyte diameter, and collagenous fiber area in the PABNT and PABE groups were significantly increased, compared with values in the PABC and sham-operated groups. Chymase-like activity was markedly greater in the PABE group than in other groups.

Conclusions and Clinical Relevance—Results indicated that treatment with candesartan but not enalapril effectively prevented myocardial remodeling in dogs with experimentally induced subacute right ventricular pressure overload.

Abstract

Objective—To compare the effects of candesartan cilexetil and enalapril maleate on right ventricular myocardial remodeling in dogs with experimentally induced pulmonary stenosis.

Animals—24 Beagles.

Procedures—18 dogs underwent pulmonary arterial banding (PAB) to induce right ventricular pressure overload, and 6 healthy dogs underwent sham operations (thoracotomy only [sham-operated group]). Dogs that underwent PAB were allocated to receive 1 of 3 treatments (6 dogs/group): candesartan (1 mg/kg, PO, q 24 h [PABC group]), enalapril (0.5 mg/kg, PO, q 24 h [PABE group]), or no treatment (PABNT group). Administration of treatments was commenced the day prior to surgery; control dogs received no cardiac medications. Sixty days after surgery, right ventricular wall thickness was assessed echocardiographi-cally and plasma renin activity, angiotensin-converting enzyme activity, and angiotensin I and II concentrations were assessed; all dogs were euthanatized, and collagenous fiber area, cardiomyocyte diameter, and tissue angiotensin-converting enzyme and chymase-like activities in the right ventricle were evaluated.

Results—After 60 days of treatment, right ventricular wall thickness, cardiomyocyte diameter, and collagenous fiber area in the PABNT and PABE groups were significantly increased, compared with values in the PABC and sham-operated groups. Chymase-like activity was markedly greater in the PABE group than in other groups.

Conclusions and Clinical Relevance—Results indicated that treatment with candesartan but not enalapril effectively prevented myocardial remodeling in dogs with experimentally induced subacute right ventricular pressure overload.

Contributor Notes

Dr. Yamane's present address is Yonago Animal Medical Center, 5-6-17 Yonehara, Yonagoshi, Tottori, 683-0804, Japan.

Supported in part by Grant-in-aid for the Promotion of Science (No. 13660329).

Address correspondence to Dr. Fujii.