PARACRINE REGULATION OF THE RENAL MICROCIRCULATION

There has been an explosive growth of interest in the multiple interac ting paracrine systems that influence renal microvascular function. Th is review first discusses the membrane activation mechanisms for renal vascular control. Evidence is provided that there are differential ac tivating mechanisms regulating pre- and postglomerular arteriolar vasc ular smooth muscle cells. The next section deals with the critical rol e of the endothelium in the control of renal vascular function and cov ers the recent findings related to the role of nitric oxide and other endothelial-derived factors. This section is followed by an analysis o f the roles of vasoactive paracrine systems that have their origin fro m adjoining tubular structures. The interplay of signals between the e pithelial cells and the vascular network to provide feedback regulatio n of renal hemodynamics is developed. Because of their well-recognized contributions to the regulation of renal microvascular function, thre e major paracrine systems are discussed in separate sections. Recent f indings related to the role of intrarenally formed angiotensin II and the prominence of the AT(1) receptors are described. The possible cont ribution of purinergic compounds is then discussed. Recognition of the emerging role of extracellular ATP operating via P-2 receptors as wel l as the more recognized functions of the P-1 receptors provides ferti le ground for further studies. In the next section, the family of vaso active arachidonic acid metabolites is described. Possibilities for a myriad of interacting functions operating both directly on vascular sm ooth muscle cells and indirectly via influences on endothelial and epi thelial cells are discussed. Particular attention is given to the more recent developments related to hemodynamic actions of the cytochrome P-450 metabolites. The final section discusses unique mechanisms that may be responsible for differential regulation of medullary blood flow by locally formed paracrine agents. Several sections provide perspect ives on the complex interactions among the multiple mechanisms respons ible for paracrine regulation of the renal microcirculation. This plur ality of regulae tory interactions highlights the need for experimenta l strategies that include integrative approaches that allow manifestat ion of indirect as well as direct influences of these paracrine system s on renal microvascular function.