Paracrine regulation of the renal microcirculation

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 AT1 receptors are described. The possible contribution of purinergic compounds is then discussed. Recognition of the emerging role of extracellular ATP operating via P2 receptors as well as the more recognized functions of the P1 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 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 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.

Increased cerebrovascular resistance in cirrhotic patients with ascites

“…Renal vascular resistance also depends on the activity of numerous neurohormonal or paracrine systems and substances with vasoconstrictor or vasodilator properties, including the sympathetic nervous system, the circulating plasma levels of angiotensin-II, arginine vasopressin and natriuretic peptides, the intrarenal synthesis of prostaglandins, the renal kallikrein-bradykinin system, and the vascular production of nitric oxide and endothelin. 30,31 The brain is, together with the kidney, the most efficient autoregulating organ in the body. 32 The most important mechanisms regulating intracerebral vascular resistance are autoregulation, chemical regulation, and metabolic regulation.…”

“…The myogenic hypothesis has been suggested as the most likely mechanism of cerebral autoregulation. 31,33 A major factor in chemical regulation is the arterial CO 2 tension. Acute hypercapnia causes cerebral vasodilation and hypocapnia causes vasoconstriction.…”

Involvement of activated prorenin in the pathogenesis of slowly progressive nephropathy in the non-clipped kidney of two kidney, one-clip hypertension

“…In the early stage of renovascular hypertension, renin secretion from the non-clipped kidney is reduced by the elevated perfusion pressure. 15 In contrast, the elevated pressure inhibits the processing of prorenin to renin, leading to accumulation of prorenin in renal juxtaglomerular cells, 16 and the tissue Ang II levels of the nonclipped kidneys rise gradually during the late stage of renovascular hypertension, 17 probably because of a prorenin-dependent mechanism. In the present study, activated prorenin and tissue Ang II levels were upregulated without any changes in (P)RR mRNA expression in the non-clipped kidneys.…”

A New Method for Evaluation of Split Renal Cortical Blood Flow with Contrast Echography

“…The kidney regulates not only the concentrations of metabolic waste products, but also systemic blood pressure via control of the extracellular fluid (1). These functions are influenced largely by changes in the regional distribution of renal blood flow (2 -5).…”