P2 receptors in regulation of renal microvascular function

Abstract

In the last 10-15 years, interest in the physiological role of P2 receptors has grown rapidly. Cellular, tissue, and organ responses to P2 receptor activation have been described in numerous in vivo and in vitro models. The purpose of this review is to provide an update of the recent advances made in determining the involvement of P2 receptors in the control of renal hemodynamics and the renal microcirculation. Special attention will be paid to work published in the last 5-6 years directed at understanding the role of P2 receptors in the physiological control of renal microvascular function. Several investigators have begun to evaluate the effects of P2 receptor activation on renal microvascular function across several species. In vivo and in vitro evidence consistently supports the hypothesis that P2 receptor activation by locally released extracellular nucleotides influences microvascular function. Extracellular nucleotides selectively influence preglomerular resistance without having an effect on postglomerular tone. P2 receptor inactivation blocks autoregulatory behavior whereas responsiveness to other vasoconstrictor agonists is retained. P2 receptor stimulation activates multiple intracellular signal transduction pathways in preglomerular smooth muscle cells and mesangial cells. Renal microvascular cells and mesangial cells express multiple subtypes of P2 receptors; however, the specific role each plays in regulating vascular and mesangial cell function remains unclear. Accordingly, the results of studies performed to date provide strong support for the hypothesis that P2 receptors are important contributors to the physiological regulation of renal microvascular and/or glomerular function.

Selective Increase in Renal Arcuate Innervation Density and Neurogenic Constriction in Chronic Angiotensin II-Infused Rats

“…[23][24][25][26][27][28][29] The density of neuromuscular junctions was not increased by Ang II, suggesting that increases in ATP release are unlikely to be the cause of the increased sensitivity of the renal arcuate arteries to nerve stimulation after treatment. However, the low incidence of neuromuscular junctions and the possibility of a diffuse distribution of purinoceptors mean that this conclusion is made cautiously.…”

ATP as a mediator of macula densa cell signalling

“…The work of this group, as well as studies from the Navar Laboratory at Tulane, set the stage for our contributions in this area [49,[82][83][84][85][86][87][88]. It should also be mentioned that around 1977, Osswald et al proposed that adenosine played a role as a mediator of TGF.…”

Telmisartan improves endothelial dysfunction and renal autoregulation in Dahl salt-sensitive rats

“…Conclusive identification of the signaling molecules that mediate autoregulation remains controversial, but it does seem clear that extracellular ATP and P2 purine receptor activation is required for autoregulatory control of renal hemodynamics. 44,45 Indeed, ATP is released from many different cell types in response to stretch, osmotic stimuli 46 and activation of P2rx1 receptors, which is an essential step in pressure-mediated afferent arteriolar vasoconstriction. Blockade of P2rx1 receptors or deletion of P2rx1 receptors in knockout mice eliminates pressure-mediated afferent arteriolar contraction.…”