Control of descending vasa recta pericyte membrane  potential by angiotensin II

Pallone, Thomas L.; Huang, J.S.T.

doi:10.1152/ajprenal.00306.2001

Cited by 47 publications

(122 citation statements)

References 45 publications

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“…Descending vasa recta arise from juxtamedullary efferent arterioles with a mean diameter of around 10 µm and are characterized by a continuous endothelium surrounded by contractile pericytes. Descending vasa recta isolated from outer medullary bundles have been shown to contract to various agonists including angiotensin II (40), an effect that is known to be modulated by Cl - (41,42). Vascular disruption of TMEM16A may thus also have an effect on renal NaCl reabsorption and the regulation of the extracellular fluid compartment as another determinant of arterial blood pressure.…”

Section: Discussionmentioning

confidence: 99%

Disruption of vascular Ca2+-activated chloride currents lowers blood pressure

Heinze¹,

Seniuk²,

Sokolov³

et al. 2014

J. Clin. Invest.

134

152

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High blood pressure is the leading risk factor for death worldwide. One of the hallmarks is a rise of peripheral vascular resistance, which largely depends on arteriole tone. Ca 2+ -activated chloride currents (CaCCs) in vascular smooth muscle cells (VSMCs) are candidates for increasing vascular contractility. We analyzed the vascular tree and identified substantial CaCCs in VSMCs of the aorta and carotid arteries. CaCCs were small or absent in VSMCs of medium-sized vessels such as mesenteric arteries and larger retinal arterioles. In small vessels of the retina, brain, and skeletal muscle, where contractile intermediate cells or pericytes gradually replace VSMCs, CaCCs were particularly large. Targeted disruption of the calcium-activated chloride channel TMEM16A, also known as ANO1, in VSMCs, intermediate cells, and pericytes eliminated CaCCs in all vessels studied. Mice lacking vascular TMEM16A had lower systemic blood pressure and a decreased hypertensive response following vasoconstrictor treatment. There was no difference in contractility of medium-sized mesenteric arteries; however, responsiveness of the aorta and small retinal arterioles to the vasoconstrictioninducing drug U46619 was reduced. TMEM16A also was required for peripheral blood vessel contractility, as the response to U46619 was attenuated in isolated perfused hind limbs from mutant mice. Out data suggest that TMEM16A plays a general role in arteriolar and capillary blood flow and is a promising target for the treatment of hypertension.

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Section: Discussionmentioning

confidence: 99%

Disruption of vascular Ca2+-activated chloride currents lowers blood pressure

Heinze¹,

Seniuk²,

Sokolov³

et al. 2014

J. Clin. Invest.

134

152

View full text Add to dashboard Cite

show abstract

“…When exposed to ANG II, pericytes depolarize by activating a Cl Ϫ conductance, a process that gates voltage-activated Ca 2ϩ entry pathways (38,107,130,176). It is surprising is that this process apparently occurs in the juxtamedullary efferent circulation that supplies the renal medulla with blood flow but not in smooth muscle of superficial efferent arterioles (13-15, 63,64).…”

Section: Discussionmentioning

confidence: 99%

“…The physiological purpose of this axial heterogeneity is uncertain, but prior observations that L-channel antagonists enhance medullary blood flow seem better explained (26,37,65,169). The ability to access DVR pericytes for electrophysiological examination and measurement of intracellular Ca 2ϩ transients is a recent development (107,130,175,176). Only cells from outer medullary vessels have been studied, and it remains possible that those from the inner medulla will be found to have unique properties.…”

Section: Discussionmentioning

confidence: 99%

“…4) (107,130,175,176). This seems to occur through activation of a Ca 2ϩ -sensitive Cl Ϫ conductance that shifts membrane potential away from the equilibrium potential of the K ϩ ion toward that of Cl Ϫ (107,175). An 11-pS Cl Ϫ channel has been identified in the pericyte cell membrane.…”

Section: Vasoactivity Of Dvrmentioning

confidence: 99%

“…Data are reproduced from Ref. 107. high external K ϩ concentration and the L-channel agonist BAY K 8644 are weak DVR vasoconstrictors.…”

Section: Vasoactivity Of Dvrmentioning

confidence: 99%

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Physiology of the renal medullary microcirculation

Pallone

Zhang

Rhinehart

2003

American Journal of Physiology-Renal Physiology

Self Cite

187

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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Control of descending vasa recta pericyte membrane potential by angiotensin II

Cited by 47 publications

References 45 publications

Disruption of vascular Ca2+-activated chloride currents lowers blood pressure

Disruption of vascular Ca2+-activated chloride currents lowers blood pressure

Physiology of the renal medullary microcirculation

Renal Medullary Circulation

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