This proposal examines the relationship between the prostaglandin (PG) and the renin (R) angiotensin system in the whole kidney and in isolated glomeruli. Studies will be carried out using normal animals following acute or chronic changes in renal perfusion pressure (RPP) within and below the range of renal blood flow autoregulation. The possible role these two systems play in modulating renal blood flow and sodium excretion will be explored. These objectives are pursued in three interrelated lines of investigation. The first line includes two series of protocols to determine the characteristics of PG and R release in isolated glomeruli elicited by endogenous release of arachadonic acid (AA) after stimulation of phospholipase (series 1) or when PG and R production are evoked by exogenous AA (series 2). In the second line of investigation three series of protocols are described. The first series explores renal blood flow distribution in the intact animal following acute reductions in RPP and the role of PG and R in mediating or modulating the distribution. The second series is similar to series one, but examines renal blood flow distribution after chronic (short and long term) reductions in RPP. In the third series of protocols glomeruli will be isolated from dogs after chronic decreases in RPP or from sham animals. This isolated preparation allows us to explore possible defects in the AA-PG-R cascade in both superficial and juxtamedullary glomeruli. The third line of investigation is composed of a series of protocols designed to determine the effects of unilateral reductions in RPP (both acute and chronic) changes in vascular tone mediated by generation of AII or PG in both the ipsilateral and contralateral kidneys.
Showing the most recent 10 out of 96 publications
