Endothelial Nitric Oxide in the Control of Glomerular Hemodynamics

Abstract: The afferent arteriole of the kidney is a unique vascular segment: it is the effector of the renal hemodynamic autoregulation. The use of the isolated, perfused juxtamedullary nephron preparation makes it possible to visualize the afferent arteriole while preserving its tissue surroundings and the functional integrity of the nephron.The author has developed a method to measure and evaluate fluorescence signals from the afferent arteriolar endothelium in this preparation and has measured endothelial intracellular calcium levels and endothelial nitric oxide production during various conditions in this model. Albumin, a common ingredient of perfusion media, has been shown to have considerable capacity to scavenge nitric oxide. Scavenging properties of the perfusion media are important in setting a "working level" of nitric oxide in the wall of the afferent arteriole. To examine the role of nitric oxide in renal autoregulation, different luminal pressures in the entire autoregulatory pressure range have been used and the endothelial calcium and luminal pressure were found to be inversely related. Nitric oxide production of the endothelium was enhanced by increases in perfusion pressure. Applying existing models of the production and diffusion of nitric oxide in blood vessels and by inserting measured vascular parameters, a mathematical model was created to describe pressure profile, shear stress, nitric oxide production and diffusion relationships and vascular reactivity in the afferent arteriole.In conclusion, nitric oxide, a major physiological dilator, plays a paramount role in renal autoregulation and afferent arteriolar vasoreactivity. Effective vessel wall nitric oxide levels are modulated by the luminal scavenging. Shear stress enhances the production of nitric oxide, by stimulating the endothelial nitric oxide synthase through non-calcium mediated mechanisms.