Zucker lean rats

Sixty-four male Zucker Obese (ZO) and six age-matched Zucker Lean (ZL) rats were purchased from Charles River, Inc and housed in a 12 h light/dark cycled room. Animals were cared for in accordance with the National Institutes of Health guidelines. All procedures were approved and performed in accordance with Subcommittee for Animal Safety of the Harry S Truman Veterans Administration and the Institutional Animal Care and Use Committee of the University of Missouri. All ZO rats were weighed prior to the start of the experiment and distributed into four treatment groups so that each group had a similar mean body weight. Beginning at 16 weeks of age, ZO rats received either sac/val (ZOSV) (68 mg kg⁻¹ day⁻¹), valsartan (ZOV) (31 mg kg⁻¹ day⁻¹), hydralazine (ZOH) (30 mg kg⁻¹ day⁻¹) or saline (ZOC) once daily for 10 weeks by oral gavage. Rats were gavaged at the same time each morning (6:00–7:00 a.m. central standard time). Body weights were measured every week thereafter until the end of the experiment (26 weeks of age). Untreated age-matched male ZL rats served as lean controls (ZLC). Six rats were removed from the study due to complications associated with oral gavage.

All experimental procedures were approved by the institutional animal care and use committee of Mitsubishi Tanabe Pharma Corporation (Osaka, Japan) and animal care was conducted in accordance with institutional guidelines. Male KK-A^y mice were purchased from CLEA Japan (Tokyo, Japan), and male Zucker diabetic fatty (ZDF) rats and Zucker lean (ZL) rats were purchased from Charles River Laboratories Japan (Tokyo, Japan). The animals were individually housed in plastic cages with ad libitum access to standard chow (CRF-1; Oriental Yeast Co., Ltd., Tokyo, Japan) and tap water. The animal rooms were controlled for temperature (23 ± 3°C), humidity (55 ± 20%), and a 12-h light/dark cycle. These animals were acclimated for 1 week prior to the start of the studies.