|M.Sc Student||Ovcharenko Elena|
|Subject||Role of Urotensin-II System in the Regulation of Renal|
Function: Studies in Normal Rats and in
Experimental Heart Failure
|Department||Department of Medicine||Supervisor||Professor Emeritus Joseph Winaver|
Urotensin II (U-II) and its receptor GPR-14 were originally identified in the teleost fish, and were recently shown to be present in several mammalian species. In the present study we evaluated the role of the U-II/GPR-14 system in the regulation of renal function and systemic hemodynamics in normal Wistar rats and in rats with aorto-caval fistula, an experimental model of congestive heart failure (CHF). The effects of incremental doses of human U-II (1.0- 100.0 nmole/kg) on mean arterial pressure, renal hemodynamics (by ultrasonic flowmetery) and intra-renal blood flow (by laser-Doppler methodology), as well as on renal clearance parameters, were studied. In addition, the effects of prior blockade of the nitric oxide (NO) system and prostaglandin synthesis, on the renal hemodynamic response to U-II, were evaluated in CHF rats. Finally, we studied the effects of U-II on selected cardiac parameters (by thermodilution technique) in control rats. Our findings demonstrate that U-II exerts a marked hypotensive effect both in control and CHF rats that was related to a decrease in cardiac output, at least in control animals. In CHF rats, U-II caused a significant, NO dependent, decrease in renal vascular resistance associated with an increase in renal blood flow that was related in part to an increase in medullary blood flow. U-II had no effects on renal sodium excretion either in control or in CHF rats, but led to a significant increase in glomerular filtration rate only in the CHF group. These findings suggest that the U-II/GPR-14 system participates in the control of systemic and renal hemodynamics in the rat, and that this regulation is significantly altered in experimental CHF.