Physiology of the renal medullary microcirculation

2003 ◽  
Vol 284 (2) ◽  
pp. F253-F266 ◽  
Author(s):  
Thomas L. Pallone ◽  
Zhong Zhang ◽  
Kristie Rhinehart
Keyword(s):  
Blood Flow ◽  
Contractile Function ◽  
Renal Medulla ◽  
Urinary Concentration ◽  
Vascular Bundles ◽  
Ang Ii ◽  
Physiological Mechanisms ◽  
Vasa Recta ◽  
Water Efflux ◽  
Salt And Water Balance

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− conductance that secondarily gates voltage-activated Ca2+ entry. In this respect, DVR may differ from other parts of the efferent microcirculation of the kidney. Elevation of extracellular K+ 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 Ca2+ is increased by bradykinin, a response that is inhibited by ANG II. ANG II inhibition of endothelial Ca2+ 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.

Vasoconstriction of outer medullary vasa recta by angiotensin II is modulated by prostaglandin E2

1994 ◽  
Vol 266 (6) ◽  
pp. F850-F857 ◽  
Author(s):  
T. L. Pallone
Keyword(s):  
Angiotensin Ii ◽  
Prostaglandin E2 ◽  
Regional Blood Flow ◽  
Renal Medulla ◽  
Hydraulic Pressure ◽  
Vascular Bundles ◽  
Ang Ii ◽  
Vasa Recta ◽  
Anatomical Arrangement

Vasa recta were dissected from outer medullary vascular bundles in the rat and perfused in vitro. Examination by transmission electron microscopy reveals them to be only outer medullary descending vasa recta (OM-DVR). To establish a method for systematic examination of vasoconstriction, OMDVR were perfused at 5 nl/min with collection pressure increased to 5 mmHg. Under these conditions, transmembrane volume flux was found to be near zero, and the transmural hydraulic pressure gradient was found to be < 15 mmHg. Over a concentration range of 10(-12) to 10(-8) M, abluminal application of angiotensin II (ANG II) caused graded focal vasoconstriction of OMDVR that is blocked by saralasin. Luminal application of ANG II over the same concentration range was much less effective. Abluminal application of prostaglandin E2 (PGE2) shifted the vasoconstrictor response of OMDVR to higher ANG II concentrations. PGE2 reversibly dilated OMDVR that had been preconstricted by ANG II. These results demonstrate that OMDVR are vasoactive segments. Their anatomical arrangement suggests that they play a key role in the regulation of total and regional blood flow to the renal medulla.

Renal medullary blood flow: its measurement and physiology

1986 ◽  
Vol 64 (7) ◽  
pp. 873-880 ◽  
Author(s):  
W. A. Cupples
Keyword(s):  
Blood Flow ◽  
Renal Medulla ◽  
Vascular Bundles ◽  
Medullary Blood Flow ◽  
Vasa Recta ◽  
Countercurrent Exchange ◽  
Renal Medullary Blood Flow ◽  
Urinary Concentrating Ability ◽  
Velocity Tracking ◽  
Uptake Method

The vasculature of the mammalian renal medulla is complex, having neither discrete input nor output. There is also efficient countercurrent exchange between ascending and descending vasa recta in the vascular bundles. These considerations have hampered measurement of medullary blood flow since they impose pronounced constraints on methods used to assess flow. Three main strategies have been used: (i) indicator extraction; (ii) erythrocyte velocity tracking; and (iii) indicator dilution. These are discussed with respect to their assumptions, requirements, and limitations. There is a consensus that medullary blood flow is autoregulated, albeit over a narrower pressure range than is total renal blood flow. When normalized to gram tissue weight, medullary blood flow in the dog is similar to that in the rat, on the order of 1 to 1.5 mL∙min−1∙g−1. This is considerably greater than estimated by the radioiodinated albumin uptake method which has severe conceptual and practical problems. From both theoretical and experimental evidence it ssems that urinary concentrating ability is considerably less sensitive to changes in medullary blood flow than is often assumed.

scholarly journals Urine concentrating mechanism: impact of vascular and tubular architecture and a proposed descending limb urea-Na+ cotransporter

2012 ◽  
Vol 302 (5) ◽  
pp. F591-F605 ◽  
Author(s):  
Anita T. Layton ◽  
William H. Dantzler ◽  
Thomas L. Pannabecker
Keyword(s):  
Blood Flow ◽  
Interstitial Fluid ◽  
Collecting Duct ◽  
Rat Kidney ◽  
Renal Medulla ◽  
Fluid Composition ◽  
Vascular Bundles ◽  
Vasa Recta ◽  
Countercurrent Exchange ◽  
Thin Limb

We extended a region-based mathematical model of the renal medulla of the rat kidney, previously developed by us, to represent new anatomic findings on the vascular architecture in the rat inner medulla (IM). In the outer medulla (OM), tubules and vessels are organized around tightly packed vascular bundles; in the IM, the organization is centered around collecting duct clusters. In particular, the model represents the separation of descending vasa recta from the descending limbs of loops of Henle, and the model represents a papillary segment of the descending thin limb that is water impermeable and highly urea permeable. Model results suggest that, despite the compartmentalization of IM blood flow, IM interstitial fluid composition is substantially more homogeneous compared with OM. We used the model to study medullary blood flow in antidiuresis and the effects of vascular countercurrent exchange. We also hypothesize that the terminal aquaporin-1 null segment of the long descending thin limbs may express a urea-Na+ or urea-Cl− cotransporter. As urea diffuses from the urea-rich papillary interstitium into the descending thin limb luminal fluid, NaCl is secreted via the cotransporter against its concentration gradient. That NaCl is then reabsorbed near the loop bend, raising the interstitial fluid osmolality and promoting water reabsorption from the IM collecting ducts. Indeed, the model predicts that the presence of the urea-Na+ or urea- Cl− cotransporter facilitates the cycling of NaCl within the IM and yields a loop-bend fluid composition consistent with experimental data.

Countercurrent exchange in the renal medulla

2003 ◽  
Vol 284 (5) ◽  
pp. R1153-R1175 ◽  
Author(s):  
Thomas L. Pallone ◽  
Malcolm R. Turner ◽  
Aurélie Edwards ◽  
Rex L. Jamison
Keyword(s):  
Blood Flow ◽  
Regional Blood Flow ◽  
Renal Medulla ◽  
Wall Structure ◽  
Urinary Concentration ◽  
Recent Theory ◽  
Water Abstraction ◽  
Current State ◽  
Vasa Recta ◽  
Countercurrent Exchange

The microcirculation of the renal medulla traps NaCl and urea deposited to the interstitium by the loops of Henle and collecting ducts. Theories have predicted that countercurrent exchanger efficiency is favored by high permeability to solute. In contrast to the conceptualization of vasa recta as simple “U-tube” diffusive exchangers, many findings have revealed surprising complexity. Tubular-vascular relationships in the outer and inner medulla differ markedly. The wall structure and transport properties of descending vasa recta (DVR) and ascending vasa recta (AVR) are very different. The recent discoveries of aquaporin-1 (AQP1) water channels and the facilitated urea carrier UTB in DVR endothelia show that transcellular as well as paracellular pathways are involved in equilibration of DVR plasma with the interstitium. Efflux of water across AQP1 excludes NaCl and urea, leading to the conclusion that both water abstraction and diffusion contribute to transmural equilibration. Recent theory predicts that loss of water from DVR to the interstitium favors optimization of urinary concentration by shunting water to AVR, secondarily lowering blood flow to the inner medulla. Finally, DVR are vasoactive, arteriolar microvessels that are anatomically positioned to regulate total and regional blood flow to the outer and inner medulla. In this review, we provide historical perspective, describe the current state of knowledge, and suggest areas that are in need of further exploration.

scholarly journals Inhibition of calcium signaling in descending vasa recta endothelia by ANG II

2000 ◽  
Vol 278 (4) ◽  
pp. H1248-H1255 ◽  
Author(s):  
Thomas L. Pallone ◽  
Erik P. Silldorff ◽  
Zhong Zhang
Keyword(s):  
Collecting Duct ◽  
No Production ◽  
Vascular Bundles ◽  
Thick Ascending Limb ◽  
Ang Ii ◽  
Vasomotor Tone ◽  
Medullary Thick Ascending Limb ◽  
Vasa Recta ◽  
Medullary Collecting Duct ◽  
Peak Phase

The intracellular calcium ([Ca2+]i) response of outer medullary descending vasa recta (OMDVR) endothelia to ANG II was examined in fura 2-loaded vessels. Abluminal ANG II (10− 8 M) caused [Ca2+]i to fall in proportion to the resting [Ca2+]i ( r =0.82) of the endothelium. ANG II (10− 8 M) also inhibited both phases of the [Ca2+]i response generated by bradykinin (BK, 10− 7 M), 835 ± 201 versus 159 ± 30 nM (peak phase) and 169 ± 26 versus 103 ± 14 nM (plateau phase) (means ± SE). Luminal ANG II reduced BK (10− 7 M)-stimulated plateau [Ca2+]i from 180 ± 40 to 134 ± 22 nM without causing vasoconstriction. Abluminal ANG II added to the bath after luminal application further reduced [Ca2+]i to 113 ± 9 nM and constricted the vessels. After thapsigargin (TG) pretreatment, ANG II (10− 8 M) caused [Ca2+]i to fall from 352 ± 149 to 105 ± 37 nM. This effect occurred at a threshold ANG II concentration of 10− 10 M and was maximal at 10− 8 M. ANG II inhibited both the rate of Ca2+ entry into [Ca2+]i-depleted endothelia and the rate of Mn2+ entry into [Ca2+]i-replete endothelia. In contrast, ANG II raised [Ca2+]i in the medullary thick ascending limb and outer medullary collecting duct, increasing [Ca2+]i from baselines of 99 ± 33 and 53 ± 11 to peaks of 200 ± 47 and 65 ± 11 nM, respectively. We conclude that OMDVR endothelia are unlikely to be the source of ANG II-stimulated NO production in the medulla but that interbundle nephrons might release Ca2+-dependent vasodilators to modulate vasomotor tone in vascular bundles.

Role of the renal medulla in volume and arterial pressure regulation

1997 ◽  
Vol 273 (1) ◽  
pp. R1-R15 ◽  
Author(s):  
A. W. Cowley
Keyword(s):  
Blood Flow ◽  
Arterial Pressure ◽  
Renal Blood Flow ◽  
Fluid Pressure ◽  
Regulatory System ◽  
Renal Medulla ◽  
Water Excretion ◽  
Vasa Recta ◽  
Pressure Natriuresis ◽  
Total Renal Blood Flow

The original fascination with the medullary circulation of the kidney was driven by the unique structure of vasa recta capillary circulation, which Berliner and colleagues (Berliner, R. W., N. G. Levinsky, D. G. Davidson, and M. Eden. Am. J. Med. 24: 730-744, 1958) demonstrated could provide the economy of countercurrent exchange to concentrate large volumes of blood filtrate and produce small volumes of concentrated urine. We now believe we have found another equally important function of the renal medullary circulation. The data show that it is indeed the forces defined by Starling 100 years ago that are responsible for the pressure-natriuresis mechanisms through the transmission of changes of renal perfusion pressure to the vasa recta circulation. Despite receiving only 5-10% of the total renal blood flow, increases of blood flow to this region of the kidney cause a washout of the medullary urea gradient and a rise of the renal interstitial fluid pressure. These forces reduce tubular reabsorption of sodium and water, leading to a natriuresis and diuresis. Many of Starling's intrinsic chemicals, which he named "hormones," importantly modulate this pressure-natriuresis response by altering both the sensitivity and range of arterial pressure around which these responses occur. The vasculature of the renal medulla is uniquely sensitive to many of these vasoactive agents. Finally, we have found that the renal medullary circulation can play an important role in determining the level of arterial pressure required to achieve long-term fluid and electrolyte homeostasis by establishing the slope and set point of the pressure-natriuresis relationship. Measurable decreases of blood flow to the renal medulla with imperceptible changes of total renal blood flow can lead to the development of hypertension. Many questions remain, and it is now evident that this is a very complex regulatory system. It appears, however, that the medullary blood flow is a potent determinant of both sodium and water excretion and signals changes in blood volume and arterial pressure to the tubules via the physical forces that Professor Starling so clearly defined 100 years ago.

scholarly journals Two-compartment model of inner medullary vasculature supports dual modes of vasopressin-regulated inner medullary blood flow

2010 ◽  
Vol 299 (1) ◽  
pp. F273-F279 ◽  
Author(s):  
Julie Kim ◽  
Thomas L. Pannabecker
Keyword(s):  
Blood Flow ◽  
Blood Flow Rate ◽  
Outer Zone ◽  
Compartment Model ◽  
Transverse Dimension ◽  
Vessel Diameter ◽  
Functional Coupling ◽  
Vascular Bundles ◽  
Transport Pathways ◽  
Vasa Recta

The outer zone of the renal inner medulla (IM) is spatially partitioned into two distinct interstitial compartments in the transverse dimension. In one compartment (the intercluster region), collecting ducts (CDs) are absent and vascular bundles are present. Ascending vasa recta (AVR) that lie within and ascend through the intercluster region (intercluster AVR are designated AVR2) participate with descending vasa recta (DVR) in classic countercurrent exchange. Direct evidence from former studies suggests that vasopressin binds to V1 receptors on smooth muscle-like pericytes that regulate vessel diameter and blood flow rate in DVR in this compartment. In a second transverse compartment (the intracluster region), DVR are absent and CDs and AVR are present. Many AVR of the intracluster compartment exhibit multiple branching, with formation of many short interconnecting segments (intracluster AVR are designated AVR1). AVR1 are linked together and connect intercluster DVR to AVR2 by way of sparse networks. Vasopressin V2 receptors regulate multiple fluid and solute transport pathways in CDs in the intracluster compartment. Reabsorbate from IMCDs, ascending thin limbs, and prebend segments passes into AVR1 and is conveyed either upward toward DVR and AVR2 of the intercluster region, or is retained within the intracluster region and is conveyed toward higher levels of the intracluster region. Thus variable rates of fluid reabsorption by CDs potentially lead to variable blood flow rates in either compartment. Net flow between the two transverse compartments would be dependent on the degree of structural and functional coupling between intracluster vessels and intercluster vessels. In the outermost IM, AVR1 pass directly from the IM to the outer medulla, bypassing vascular bundles, the primary blood outflow route. Therefore, two defined vascular pathways exist for fluid outflow from the IM. Compartmental partitioning of V1 and V2 receptors may underlie vasopressin-regulated functional compartmentation of IM blood flow.

scholarly journals Increased activity and expression of Ca2+-dependent NOS in renal cortex of ANG II-infused hypertensive rats

1999 ◽  
Vol 277 (5) ◽  
pp. F797-F804 ◽  
Author(s):  
So Yeon Chin ◽  
Kailash N. Pandey ◽  
Shang-Jin Shi ◽  
Hiroyuki Kobori ◽  
Carol Moreno ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Renal Cortex ◽  
Renal Medulla ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Hypertensive Rats ◽  
Differential Distribution ◽  
Cortical Blood Flow ◽  
Renal Cortical Blood Flow

We have previously demonstrated that nitric oxide (NO) exerts a greater modulatory influence on renal cortical blood flow in ANG II-infused hypertensive rats compared with normotensive rats. In the present study, we determined nitric oxide synthase (NOS) activities and protein levels in the renal cortex and medulla of normotensive and ANG II-infused hypertensive rats. Enzyme activity was determined by measuring the rate of formation ofl-[14C]citrulline froml-[14C]arginine. Western blot analysis was performed to determine the regional expression of endothelial (eNOS), neuronal (nNOS), and inducible (iNOS) isoforms in the renal cortex and medulla of control and ANG II-infused rats. Male Sprague-Dawley rats were prepared by the infusion of ANG II at a rate of 65 ng/min via osmotic minipumps implanted subcutaneously for 13 days and compared with sham-operated rats. Systolic arterial pressures were 127 ± 2 and 182 ± 3 mmHg in control ( n = 13) and ANG II-infused rats ( n = 13), respectively. The Ca2+-dependent NOS activity, expressed as picomoles of citrulline formed per minute per gram wet weight, was higher in the renal cortex of ANG II-infused rats (91 ± 11) than in control rats (42 ± 12). Likewise, both eNOS and nNOS were markedly elevated in the renal cortex of the ANG II-treated rats. In both groups of rats, Ca2+-dependent NOS activity was higher in the renal medulla than in the cortex; however, no differences in medullary NOS activity were observed between the groups. Also, no differences in medullary eNOS levels were observed between the groups; however, medullary nNOS was decreased by 45% in the ANG II-infused rats. For the Ca2+-independent NOS activities, the renal cortex exhibited a greater activity in the control rats (174 ± 23) than in ANG II-infused rats (101 ± 10). Similarly, cortical iNOS was greater by 47% in the control rats than in ANG II-treated rats. No differences in the activity were found for the renal medulla between the groups. There was no detectable signal for iNOS in the renal medulla for both groups. These data indicate that there is a differential distribution of NOS activity, with the Ca2+-dependent activity and protein expression higher in the renal cortex of ANG II-infused rats compared with control rats, and support the hypothesis that increased constitutive NOS activity exerts a protective effect in ANG II-induced hypertension to maintain adequate renal cortical blood flow.

Effect of norepinephrine and acetylcholine on outer medullary descending vasa recta

1995 ◽  
Vol 269 (2) ◽  
pp. H710-H716 ◽  
Author(s):  
S. Yang ◽  
E. P. Silldorff ◽  
T. L. Pallone
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Regional Blood Flow ◽  
Renal Medulla ◽  
Cholinergic Innervation ◽  
Vascular Bundles ◽  
Nitric Oxide Synthase Inhibitor ◽  
Vasa Recta ◽  
Oxide Synthase

To examine their responsiveness to norepinephrine (NE) and acetylcholine (ACh), outer medullary descending vasa recta (OMDVR) have been dissected from vascular bundles of the rat and perfused in vitro. Abluminal application of NE produced graded vasoconstriction in a concentration range of 10(-9)-10(-6) M. When applied with NE, ACh at concentrations of 10(-8)-10(-5) M dilated NE-preconstricted OMDVR. In contrast, ACh applied in the absence of NE caused vasoconstriction. ACh-induced vasodilation was blocked by addition of the nitric oxide synthase inhibitor N omega-nitro-L-arginine (L-NNA, 2 x 10(-4) M). L-NNA in the absence of ACh enhanced NE-induced vasoconstriction. Supraphysiological (10(-3) M) L-arginine (L-Arg) reversed the effects of L-NNA, and abluminal application of L-NNA alone resulted in OMDVR vasoconstriction. At concentrations of 10(-6)-10(-3) M, abluminal application of L-Arg produced graded vasodilation of NE-constricted OMDVR. These results suggest that adrenergic and cholinergic innervation could influence OMDVR vasomotor tone to modulate total and regional blood flow to the renal medulla. The data also favor a role for the activity of constitutively expressed nitric oxide synthase to modulate OMDVR vasoactivity.

Autoregulation of blood flow in renal medulla of the rat: no role for angiotensin II

1988 ◽  
Vol 66 (6) ◽  
pp. 833-836 ◽  
Author(s):  
W. A. Cupples ◽  
D. J. Marsh
Keyword(s):  
Blood Flow ◽  
Angiotensin Ii ◽  
Lower Limit ◽  
Enzyme Inhibitor ◽  
Renal Medulla ◽  
Converting Enzyme ◽  
Converting Enzyme Inhibitor ◽  
Upper Limit ◽  
Vasa Recta

Autoregulation of blood flow was assessed by a dual-slit technique in descending and ascending vasa recta of the exposed renal papillae of antidiuretic rats. There was complete autoregulation of blood flow in descending vasa recta. The lower limit of autoregulation was approximately 85 mmHg (1 mmHg = 133.3 Pa) and the upper limit was greater then 160 mmHg. Auto-regulation in ascending vasa recta was also good. To test the role of angiotensin II in this autoregulation, the converting enzyme inhibitor captopril was infused. Captopril had no effect on autoregulation of blood flow in either descending or ascending vasa recta. We conclude that blood flow in vasa recta of renal medulla is efficiently autoregulated and that this autoregulation is independent of angiotensin II

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