Physiology of the renal medullary microcirculation

Abstract

Pallone, Thomas L., Zhong Zhang, and Kristie Rhinehart. Physiology of the renal medullary microcirculation. Am J Physiol Renal Physiol 284: F253-F266, 2003; 10.1152/ajprenal.00304.2002.-Perfusion of the renal medulla plays an important role in salt and water balance. Pericytes are smooth muscle-like cells that impart contractile function to descending vasa recta (DVR), the arteriolar segments that supply the medulla with blood flow. DVR contraction by ANG II is mediated by depolarization resulting from an increase in plasma membrane Cl Ϫ conductance that secondarily gates voltage-activated Ca 2ϩ entry. In this respect, DVR may differ from other parts of the efferent microcirculation of the kidney. Elevation of extracellular K ϩ constricts DVR to a lesser degree than ANG II or endothelin-1, implying that other events, in addition to membrane depolarization, are needed to maximize vasoconstriction. DVR endothelial cytoplasmic Ca 2ϩ is increased by bradykinin, a response that is inhibited by ANG II. ANG II inhibition of endothelial Ca 2ϩ signaling might serve to regulate the site of origin of vasodilatory paracrine agents generated in the vicinity of outer medullary vascular bundles. In the hydropenic kidney, DVR plasma equilibrates with the interstitium both by diffusion and through water efflux across aquaporin-1. That process is predicted to optimize urinary concentration by lowering blood flow to the inner medulla. To optimize urea trapping, DVR endothelia express the UT-B facilitated urea transporter. These and other features show that vasa recta have physiological mechanisms specific to their role in the renal medulla. vasa recta; perfusion; hypertension; oxygenation; urinary concentration; patch clamp; calcium; fura 2 THE MICROCIRCULATION OF THE kidney is regionally specialized. In the cortex, afferent and efferent arterioles govern the driving forces that promote glomerular filtration. A dense peritubular capillary plexus arising from efferent arterioles surrounds the proximal and distal convoluted tubules to accommodate enormous reabsorption of glomerular filtrate. In contrast, vasa recta serve needs specific to the medulla. Through the counterflow arrangement of descending (DVR) and ascending vasa recta (AVR), countercurrent exchange traps NaCl and urea deposited to the interstitium by collecting ducts and the loops of Henle. This is vital to maintain corticomedullary osmotic gradients but conflicts with the need to supply nutrient blood flow to medullary tissue. Metabolic substrates that enter the medulla in DVR blood diffuse to the AVR to be shunted back to the cortex. To deal with the threat of medullary hypoxia resulting from this process, the kidney has evolved a capacity to exert subtle control over regional perfusion of the outer and inner medulla. The details are far from clear, but much experimental evidence points to the complex interactions of many autocoids and paracrine agents to modulate vasomotor tone at various sites along the microvascular circuit. The goal of this review is to summarize ...

Response of descending vasa recta to luminal pressure

“…NO production by DVR endothelia might also favor saliuresis because NO inhibits NaCl reabsorption at multiple sites along the nephron (22,28). The possibility of such NO-mediated signaling between tubular and vascular structures in the kidney has been frequently postulated (7,9,22,28,31,34).…”

“…The vessel was warmed to 37°C and loaded for 20 min with 10 M DAF-2DA ester. We previously showed that DAF-2 loads into both endothelia and pericytes and increases its emission at 530 nm during excitation between 450 and 500 nm without a spectral shift (34,36).…”

“…DVR were loaded with the Ca 2ϩ -sensitive fluorescent indicator fura 2 by exposure to bath containing 2 M fura 2 AM ester (Molecular Probes, Eugene, OR) for 20 min (25,27). We previously showed that fura 2 preferentially loads into endothelial cells rather than pericytes (34). For measurement of [Ca 2ϩ ]CYT, fura 2-loaded DVR were excited using a 350/380-nm dual-wavelength combination.…”

“…Bioavailability of NO is modulated through its reaction with superoxide to form peroxynitrite. We previously observed that bradykininstimulated DVR endothelial NO can be enhanced by the cell-permeant superoxide dismutase mimetic tempol (34,36). We chose to test the effect of tempol on pressure-stimulated NO generation because reactive oxygen species have been found to play a role in mechanosensitive signaling in other endothelia (1).…”

“…They originate as branches of the juxtamedullary efferent arteriole and traverse the outer medulla in vascular bundles to supply the inner and outer medulla. Their radial distribution within vascular bundles implies that they distribute and regulate regional blood flow within the medulla (34). DVR are lined with a continuous endothelium and enveloped by smooth muscle/pericytes that impart contractility (30,33).…”