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

Pallone, Thomas L.; Silldorff, Erik P.; Zhang, Zhong

doi:10.1152/ajpheart.2000.278.4.h1248

Cited by 32 publications

(61 citation statements)

References 38 publications

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“…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).…”

Section: Discussionmentioning

confidence: 99%

“…To quantify changes in vessel diameter, microperfusion experiments were monitored with a video camera (Dage, MTI) and recorded on tape (Panasonic AG 1960 VCR). As previously described (30,31), tapes were played back to measure DVR outer diameter with calipers.…”

Section: Isolation and Microperfusion Of Dvrmentioning

confidence: 99%

“…The backgroundsubtracted ratio of fluorescent emission (R 350/380) was calculated for conversion to the equivalent intracellular calcium concentration assuming a dissociation constant for fura 2 at 37°C of 224 nM. R max and Rmin were measured as previously described by exposing vessels to buffer containing 5 mM CaCl2 or 0 mM CaCl2, 0.5 mM EGTA, respectively, along with 10 M calcium ionophore (31).…”

Section: Isolation and Microperfusion Of Dvrmentioning

confidence: 99%

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Response of descending vasa recta to luminal pressure

Zhang¹,

Pallone²

2004

American Journal of Physiology-Renal Physiology

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Zhang, Zhong, and Thomas L. Pallone. Response of descending vasa recta to luminal pressure. Am J Physiol Renal Physiol 287: F535-F542, 2004. First published May 4, 2004 10.1152/ajprenal. 00394.2003.-We tested whether luminal perfusion and pressurization induce an endothelial cytoplasmic Ca 2ϩ ([Ca 2ϩ ]CYT) response in descending vasa recta (DVR). DVR isolated from the rat outer medulla were cannulated and subjected to free-flow microperfusion (5 nl/min); the onset of which increased [Ca 2ϩ ]CYT from a baseline of 76 Ϯ 13 to 221 Ϯ 65 nM. A graded increase in luminal pressure from 0 to 45 mmHg in stopped-flow experiments induced a parallel increase in [Ca 2ϩ ]CYT from a baseline of 74 Ϯ 24 to 194 Ϯ 33 nM at 45 mmHg, with a tendency for [Ca 2ϩ ]CYT to plateau at pressures Ͼ25 mmHg. The removal of extracellular Ca 2ϩ and blockade by either La 3ϩ (10 M) or SKF-96365 (100 M) eliminated the response. Luminal pressurization to 25 mmHg increased nitric oxide (NO) generation, a response blocked by NO synthase inhibition or removal of extracellular Ca 2ϩ . The NO generation was not affected by the superoxide dismutase mimetic tempol. We conclude that DVR endothelia are mechanosensitive and respond to luminal pressure by elevating [Ca 2ϩ ]CYT and generating NO. That response might augment medullary perfusion and saliuresis. medulla; kidney; microcirculation; shear; fura 2; 4,5-diaminofluoroscein DESCENDING VASA RECTA (DVR) are small generation resistance vessels that carry blood flow from the cortex to the medulla of the kidney. 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). The importance of endothelial secretion of paracrine mediators to modulate adjacent smooth muscle is well established. Motivated by the importance of nitric oxide (NO) secretion in the maintenance of renal medullary perfusion and blood pressure (7,22,23,28) we employed microperfusion and fluorescence microscopy to test whether DVR endothelial cytoplasmic Ca 2ϩ ([Ca 2ϩ ] CYT ) is affected by the transmural pressure gradient imposed across the DVR wall. We exploited the property of the Ca 2ϩ -sensitive probe, fura 2, to preferentially load into DVR endothelia (while sparing pericytes) to quantify the effect of raising intraluminal pressure on [Ca 2ϩ ] CYT . In addition, the probe 4,5-diaminofluorescein (DAF-2), which increases fluorescence when covalently modified by NO, was used to monitor NO generation. The results verify that an increase in luminal pressure is accompanied by a parallel rise in DVR endothelial [Ca 2ϩ ] CYT and a robust increase in NO synthesis.NO functions as a vasodilator and "endogenous diuretic" (23, 28). We hypothesize that the vasa recta endothelium might serve a...

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Section: Discussionmentioning

confidence: 99%

Section: Isolation and Microperfusion Of Dvrmentioning

confidence: 99%

Section: Isolation and Microperfusion Of Dvrmentioning

confidence: 99%

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Response of descending vasa recta to luminal pressure

Zhang¹,

Pallone²

2004

American Journal of Physiology-Renal Physiology

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“…An unexpected finding is that the vasoconstrictor ANG II suppresses basal Ca 2ϩ and inhibits BK-, acetylcholine-, thapsigargin-, and cyclopiazonic acid-induced Ca 2ϩ responses in DVR endothelia (Fig. 7, B and C) (114,130). This is surprising for several reasons.…”

Section: Role Of Dvr Endothelia In the Regulation Of Vasoactivitymentioning

confidence: 94%

“…These agents induce durable constriction that does not wane and is only slowly reversible after washout. ANG II is also a consistent constrictor that, on average, reduces luminal diameter of microperfused vessels by 40-60% (104,114,129). As in cortical vessels, thromboxanes are partially responsible for mediation of ANG II DVR constriction (140,143,164,165).…”

Section: Vasoactivity Of Dvrmentioning

confidence: 99%

Physiology of the renal medullary microcirculation

Pallone

Zhang

Rhinehart

2003

American Journal of Physiology-Renal Physiology

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186

193

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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 ...

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Renal Medullary Circulation

Pallone

Edwards

Mattson

2012

Comprehensive Physiology

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The renal medullary microcirculation is a distinctive arrangement of blood vessels that serve multiple functions in the renal medulla. This article begins with a description of the unique anatomy of this vascular bed and the role it plays in transport and countercurrent exchange in the medulla. A segment of the review is then devoted to the important role mathematical modeling has played in the understanding of this vascular bed's function. Succeeding sections focus upon the hematocrit in the vasa recta capillaries and methods utilized to assess blood flow in the renal medulla. An extensive portion of the article is then devoted to the regulation of the medullary circulation, from ion channel architecture to neurohormonal signaling. Finally, we discuss the importance of the renal medullary circulation in the regulation of fluid and electrolyte homeostasis and arterial blood pressure regulation.

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

Cited by 32 publications

References 38 publications

Response of descending vasa recta to luminal pressure

Response of descending vasa recta to luminal pressure

Physiology of the renal medullary microcirculation

Renal Medullary Circulation

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