Abstract 1622: Chronic Urotensin II Alters Phospholamban and SERCA2 in a Model of Congestive Heart Failure
The role of Urotensin II in the progression congestive heart failure is not yet fully understood. Current literature has reported the effects of acute administration of UTII, in the modulation of Ca2+ handling, but to date very little information is available regarding the effects of exposure in a chronic setting. Therefore, the purpose of this study was to determine the effects of chronic UTII administration on expression of calcium regulatory proteins in rats with or without aorta-caval fistula. Aorta-caval fistula (VO) was created by 18g needle puncture across the infrarenal aorta and vena cava in Sprague-Dawley rats (n =8). In a second group of animals (n =8), the fistula was created immediately followed by inserting of osmotic pumps delivering UTII at a rate of 300pmol/kg/day (PV). Finally, a third group of animals were subjected to UTII without the fistula (Pump, n =8). After 4 weeks cardiac performance, as assesed by ±dP/dt, was decreased in the Pump and VO groups. These values were restored to near control levels in the PV group. Western blot analysis of left ventricular homogenates demonstrated differential changes in the expression Ca2+ handling proteins phospholamban (PLN), SERCA2, and Na/Ca2+ exchanger (NCX) as well as the SERCA2/PLN ratio. Changes in Ca2+ handling have been suggested to be a major influence on the progression of congestive heart failure. In the pump group, the substantial increase in PLN accompanied by a decrease in SERCA2 expression, may indicate one mechanism leading to the decreased cardiac performance. However, animals in the VO group showed decreased expression of PLN only and may reflect the changes in contractility seen in this model associated with a more efficient Ca2+ cycling. The data reported here allows us to suggest that UTII may differentially influence Ca2+ handling in the progression of heart failure.