Paracrine Regulation of the Renal Microcirculation.
Navar, L. G., E. W. Inscho, D. S. A. Majid, J. D. Imig, L. M. Harrison-
Bernard, and K. D. Mitchell.
Dept. of Physiology, Tulane University Medical Center, 5639, New Orleans,
LA 70112
APStracts 2:0027P, 1996.
ABSTRACT
There has been an explosive growth of interest in the multiple interacting
paracrine systems that influence renal microvascular function. This review
first discusses the membrane activation mechanisms for renal vascular control.
Evidence is provided that there are differential activating mechanisms
regulating pre- and postglomerular arteriolar vascular smooth muscle cells.
The next section deals with the critical role of the endothelium in the
control of renal vascular function and covers the recent findings related to
the role of nitric oxide and other endothelial-derived factors. This section
is followed by an analysis of the roles of vasoactive paracrine systems that
have their origin from adjoining tubular structures. The interplay of signals
between the epithelial cells and the vascular network to provide feedback
regulation of renal hemodynamics is developed. Because of their well-
recognized contributions to the regulation of renal microvascular function,
three major paracrine systems are discussed in separate sections. Recent
findings related to the role of intrarenally formed angiotensin II and the
prominence of the AT[inf]1[r] receptors are described. The possible
contribution of purinergic compounds is then discussed. Recognition of the
emerging role of extracellular ATP operating via P[inf]2[r] receptors as well
as the more recognized functions of the P[inf]1[r] receptors provides fertile
ground for further studies. In the next section, the family of vasoactive
arachidonic acid metabolites is described. Possibilities for a myriad of
interacting functions operating both directly on vascular smooth muscle cells
and indirectly via influences on endothelial and epithelial cells are
discussed. Particular attention is given to the more recent developments
related to hemodynamic actions of the cytochrome [i]P[r]-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 perspectives on the complex interactions
among the multiple mechanisms responsible for paracrine regulation of the
renal microcirculation. This plurality of regulatory interactions highlights
the need for experimental strategies that include integrative approaches that
allow manifestation of indirect as well as direct influences of these
paracrine systems on renal microvascular function.
APS Manuscript Number P27-5.
Article publication pending April 1996, Physiological Reviews.
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 5 November 1996