Integrating multiple paracrine regulators of renal microvascular dynamics.
There has been tremendous growth in our knowledge about the multiple interacting mechanisms that regulate renal microvascular function. Paracrine signals originating from endothelial and epithelial cells exert profound influences on the basal tone and reactivity of the pre- and postglomerular arterioles. Selective responsiveness of these arterioles to various stimuli is possible because of differential activating mechanisms in vascular smooth muscle cells of afferent and efferent arterioles. Afferent arterioles rely predominantly on voltage-dependent calcium channels, while efferent arterioles utilize other mechanisms for calcium entry as well as intracellular calcium mobilization. The autoregulatory responses of preglomerular arterioles exemplify the selectivity of these complex control mechanisms. The myogenic mechanism responds to increases in renal perfusion pressure through "stretch-activated" cation channels that lead to depolarization, calcium entry, and vascular contraction. Autoregulatory efficiency is enhanced by the tubuloglomerular feedback (TGF) mechanism which responds to flow-dependent changes in tubular fluid composition at the level of the macula densa and transmits signals to the afferent arterioles to alter the activation state of voltage-dependent calcium channels. Recent studies have implicated extracellular ATP as one paracrine factor mediating TGF and autoregulatory related signals to the afferent arterioles. Other paracrine agents including nitric oxide, angiotensin II, adenosine, and arachidonic acid metabolites modulate vascular responsiveness in order to maintain an optimal balance between the metabolically determined reabsorptive capabilities of the tubules and the hemodynamically dependent filtered load.
Navar
L G
LG
Department of Physiology, Tulane University School of Medicine, New Orleans, Louisiana 70112, USA.
D000818:Animals; D002118:Calcium / Q000502:physiology; D005246:Feedback; D006706:Homeostasis; D006801:Humans; D007606:Juxtaglomerular Apparatus / Q000502:physiology; D007668:Kidney / Q000098:blood supply*; D007678:Kidney Glomerulus / Q000502:physiology; D007684:Kidney Tubules / Q000502:physiology; D008833:Microcirculation; D012039:Regional Blood Flow
D002118:Calcium