Submitted on December 13, 2006
Accepted on March 5, 2007
Cardiovascular dysfunction in Zucker obese and Zucker diabetic fatty rats: the role of hydronephrosis
Susan A Marsh1, Pamela C. Powell1, Anupam Agarwal2, louis J. Dell'Italia1, and John C. Chatham1*
1 Medicine/Cardiovascular Diease, University of Alabama at Birmingham, Birmingham, Alabama, United States
2 Medicine/Nephrology, University of Alabama at Birmingham, Birmingham, Alabama, United States
* To whom correspondence should be addressed. E-mail: jchatham{at}uab.edu.
Recent studies in our laboratory using the Zucker obese and Zucker Diabetic Fatty (ZDF) rat models resulted in unexpectedly high mortality rates in all genotypes including healthy homozygous lean Zucker rats, possibly due to renal dysfunction. Therefore, we evaluated left ventricular (LV) and kidney morphology and function in young Zucker and Zucker Diabetic Fatty obese (ZO, ZDFO), homozygous Zucker/ZDF lean (ZL), and Sprague-Dawley (SD) rats. Hydronephrosis was evident in ZL, ZO and ZDFO kidneys but not SD. ZDFO exhibited impaired LV shortening and relaxation with increased arterial stiffness. LV wall thickness was lower and LV end-systolic wall stress was higher in ZDFO compared to SD. Plasma Ang II was lower in ZO and ZDFO and norepinephrine was higher in ZDFO than SD controls. Covariate analysis indicated that arterial stiffness and diastolic dysfunction was associated with hyperglycemia but not renal dysfunction; whereas, LV end-systolic wall stress was associated with renal dysfunction. Reduced renal parenchyma with hydronephrosis may account for the lower Ang II levels in Zucker rats. The presence of hydronephrosis and its association with LV dysfunction potentially limits the ZDF model for study the effects of diabetes on renal and cardiovascular function.
