Response of isolated rat descending vasa recta to bradykinin

Pallone, Thomas L.; Silldorff, Erik P.; Cheung, Joseph Y.

doi:10.1152/ajpheart.1998.274.3.h752

Cited by 26 publications

(57 citation statements)

References 21 publications

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“…As expected, BK generates a peak-and-plateau Ca 2ϩ response, enhances NO generation (Fig. 8), and induces vasodilation (112,129,130). 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.…”

Section: Role Of Dvr Endothelia In the Regulation Of Vasoactivitysupporting

confidence: 73%

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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Section: Role Of Dvr Endothelia In the Regulation Of Vasoactivitysupporting

confidence: 73%

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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“…Exposure of HepG2 cells to ketamine for 6 and 24 h significantly decreased the bradykininenhanced calcium mobilization. Bradykinin increases calcium influx through stimulation of the bradykinin-B2 receptor (Pallone et al, 1998). This endogenous bradykinin-B2 receptor is found in hepatocytes (Yayama et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

Cytoskeleton Interruption in Human Hepatoma HepG2 Cells Induced by Ketamine Occurs Possibly through Suppression of Calcium Mobilization and Mitochondrial Function

Chang¹,

Chen²,

Chen

2008

Drug Metab Dispos

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ABSTRACT:Ketamine is an intravenous anesthetic agent often used for inducing and maintaining anesthesia. Cytoskeletons contribute to the regulation of hepatocyte activity of drug biotransformation. In this study, we attempted to evaluate the effects of ketamine on F-actin and microtubular cytoskeletons in human hepatoma HepG2 cells and its possible molecular mechanisms. Exposure of HepG2 cells to ketamine at <100 M, which corresponds to clinically relevant concentrations for 1, 6, and 24 h, did not affect cell viability. Meanwhile, administration of therapeutic concentrations of ketamine obviously interrupted F-actin and microtubular cytoskeletons. In parallel, levels of intracellular calcium concentration-and timedependently decreased after ketamine administration. Analysis by confocal microscopy further revealed that ketamine suppressed calcium mobilization from an extracellular buffer into HepG2 cells.Exposure to ketamine decreased cellular ATP levels. The mitochondrial membrane potential and complex I NADH dehydrogenase activity were both reduced after ketamine administration. Ketamine did not change the production of actin or microtubulin mRNA in HepG2 cells. Consequently, ketamine-caused cytoskeletal interruption led to suppression of CYP3A4 expression and its metabolizing activity. Therefore, this study shows that therapeutic concentrations of ketamine can disrupt F-actin and microtubular cytoskeletons possibly through suppression of intracellular calcium mobilization and cellular ATP synthesis due to downregulation of the mitochondrial membrane potential and complex I enzyme activity. Such disruption of the cytoskeleton may lead to reductions in CYP3A4 activity in HepG2 cells.

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“…The focus of these studies has been on the larger diameter vasa recta vessels of the outer medulla for reasons related to the unique structure and function of the medullary vasa recta circulation. Before the results of these studies are reviewed, it is important to first appreciate the microvascular anatomy of the renal medulla, as described in detail by others (3,4,40,44,64,(81)(82)(83)127). In brief, it is recognized that blood flow to the medulla of mammalian kidneys is supplied by postglomerular microvessels derived from juxtamedullary glomeruli, the deep glomeruli of the inner cortex that receive their blood supply from the interlobular branches of the arcuate arteries, as described by Kaissling and Kriz (39).…”

Section: Evidence For Paracrine and Autocrine No Function In The Renamentioning

confidence: 99%

“…For example, these vessels have been shown to respond to vasoconstrictors such as ANG II, as shown in Fig. 3A (85), AVP (124), and endothelin (112), as well as vasodilators such as bradykinin (83), prostaglandin E 2 (112), and adenosine (111). The ability of the DVR to behave like small arterioles accounts for the ability of the medullary flow to be controlled independently from the cortical circulation when vasoactive substances are endogenously released or infused.…”

Section: Evidence For Paracrine and Autocrine No Function In The Renamentioning

confidence: 99%

Role of renal NO production in the regulation of medullary blood flow

Cowley

Mori

Mattson

et al. 2003

American Journal of Physiology-Regulatory, Integrative and Comp

175

202

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. Role of renal NO production in the regulation of medullary blood flow. Am J Physiol Regul Integr Comp Physiol 284: R1355-R1369, 2003 10.1152/ajpregu.00701.2002The unique role of nitric oxide (NO) in the regulation of renal medullary function is supported by the evidence summarized in this review. The impact of reduced production of NO within the renal medulla on the delivery of blood to the medulla and on the long-term regulation of sodium excretion and blood pressure is described. It is evident that medullary NO production serves as an important counterregulatory factor to buffer vasoconstrictor hormoneinduced reduction of medullary blood flow and tissue oxygen levels. When NO synthase (NOS) activity is reduced within the renal medulla, either pharmacologically or genetically [Dahl salt-sensitive (S) rats], a super sensitivity to vasoconstrictors develops with ensuing hypertension. Reduced NO production may also result from reduced cellular uptake of L-arginine in the medullary tissue, resulting in hypertension. It is concluded that NO production in the renal medulla plays a very important role in sodium and water homeostasis and the long-term control of arterial pressure. renal medulla; Dahl salt-sensitive rats; hypertension; L-arginine THE RENAL MEDULLARY CIRCULATION is now recognized to be of importance for reasons that extend far beyond providing the economy of countercurrent exchange to concentrate large volumes of filtrate to produce small volumes of concentrated urine. It is now recognized that medullary blood flow (MBF) can play an important role in determining long-term levels of arterial pressure and that 15-30% reductions of blood flow to the renal medulla in the face of imperceptibly small changes of total renal blood flow can lead to the development of hypertension (16,21). Evidence is reviewed showing that nitric oxide (NO) plays a unique role in the acute and chronic regulation of renal MBF, sodium homeostasis, and arterial pressure. More specifically, the role of NO in the regulation of MBF, in linking tubular metabolic needs with delivery of nutrients and as a counterregulatory system to protect the medulla from the consequences of underperfusion, are the focus of this review. The influence of NO on the renal cortex and such issues that relate to pressure-natriuresis, autoregulation of total renal blood flow, tubuloglomerular feedback, and glomerular filtration rate (GFR) regulation are important subjects of renal function that either have been reviewed by others (2,29,43,55,96) or are beyond the scope of this relatively brief review.

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Response of isolated rat descending vasa recta to bradykinin

Cited by 26 publications

References 21 publications

Physiology of the renal medullary microcirculation

Physiology of the renal medullary microcirculation

Cytoskeleton Interruption in Human Hepatoma HepG2 Cells Induced by Ketamine Occurs Possibly through Suppression of Calcium Mobilization and Mitochondrial Function

Role of renal NO production in the regulation of medullary blood flow

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