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Olmesartan improves left ventricular function in pressure-overload hypertrophied rat heart by blocking angiotensin II receptor with synergic effects of upregulation of angiotensin converting enzyme 2

Department of Thoracic and Cardiovascular Surgery, Hirosaki University School of Medicine, Hirosaki, Japan

Masahito Minakawa

Department of Thoracic and Cardiovascular Surgery, Hirosaki University School of Medicine, Hirosaki, Japan

Kozo Fukui

Department of Thoracic and Cardiovascular Surgery, Hirosaki University School of Medicine, Hirosaki, Japan

Yasuyuki Suzuki

Department of Thoracic and Cardiovascular Surgery, Hirosaki University School of Medicine, Hirosaki, Japan

Ikuo Fukuda

Department of Thoracic and Cardiovascular Surgery, Hirosaki University School of Medicine, Hirosaki, Japan, ikuofuku{at}cc.hirosaki-u.ac.jp

It is not clear how the blocking effect of angiotensin II receptors by olmesartan affects the functional recovery of pressure-overload hypertrophied heart. Hypertrophied heart was created by abdominal aortic banding above the celiac artery in Wistar rats at the age of eight weeks. Hypertrophied heart was excised and studied at 10 and 16 weeks after the operation (HT groups). For the last four weeks before the experiment, olmesartan (0.2 mg/kg per day) was administered subcutaneously by osmotic minipumps (Olm groups). Left ventricular function was measured by Langendorff perfusion. The levels of mRNA for angiotensin-converting enzyme (ACE), ACE2 and extracellular signal-regulated kinases (ERKs) in myocardium were analyzed by RT-PCR. Left ventricular systolic (+dP/dt_max, left ventricular systolic pressure) and diastolic functions (-dP/dt_max, tau) were impaired in HT groups, while in Olm groups they were significantly improved. The left ventricle to body weight (LV/BW) ratio increased significantly in HT groups, but in Olm groups the LV/BW ratio decreased significantly in comparison with HT groups. The ACE2 mRNA level was significantly higher in Olm groups as compared with HT groups. Plasma angiotensin II and the ERK mRNA level in HT groups increased significantly, but decreased in Olm groups in comparison with HT groups significantly. Olmesartan improved left ventricular function and hypertrophy through the increase of the ACE2 mRNA and decrease of both angiotensin II and ERK mRNA in pressure-overload rat heart.

Key Words: olmesartan • hypertrophy • angiotensin II type 1 receptor blockers • angiotensin converting enzyme 2.

This version was published on April 1, 2009

Therapeutic Advances in Cardiovascular Disease, Vol. 3, No. 2, 103-111 (2009)
DOI: 10.1177/1753944708098691


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