Role of nitric oxide in renal papillary blood flow and sodium excretion.

Mattson, David L.; Roman, Richard J.; Cowley, Allen W.

doi:10.1161/01.hyp.19.6.766

Cited by 199 publications

(143 citation statements)

References 13 publications

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“…Blockade of this receptor shifts curves of fractional sodium and water reabsorption in hypertensive rats toward normal (38,39). In addition to any direct tubular effects of NO inhibition, the increase in renal vascular resistance and decrease in RBF in L-NAME AT 2 Ϫ/Ϫ mice would support a reduction in medullary blood flow and renal interstitial hydrostatic pressure in these mice (40,41).…”

Section: Discussionmentioning

confidence: 99%

Pressure Natriuresis in AT2 Receptor–Deficient Mice with L-NAME Hypertension

Obst¹,

Groß²,

Janke

et al. 2003

Journal of the American Society of Nephrology

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Abstract. AT 2 receptor-disrupted (AT 2 Ϫ/Ϫ) mice provide a unique opportunity to investigate the cardiovascular and BP-related effects of NO depletion. This study compared the pressure-diuresis-natriuresis relationship in (AT 2 Ϫ/Ϫ) and wild-type (AT 2 ϩ/ϩ) mice after treating the animals with L-NAME (130 mg/kg body wt per day) for 1 wk. L-NAME increased mean arterial pressure (MAP) more in AT 2 Ϫ/Ϫ than in AT 2 ϩ/ϩ mice (118 Ϯ 2 versus 108 Ϯ 4 mmHg). This difference occurred even though L-NAME-treated AT 2 ϩ/ϩ mice had a greater sodium excretion than AT 2 Ϫ/Ϫ mice (10.9 Ϯ 0.5 versus 8.0 Ϯ 1.0 mol/h). The pressurenatriuresis relationship in conscious AT 2 Ϫ/Ϫ mice was shifted rightward compared with controls. RBF was decreased in AT 2 Ϫ/Ϫ compared with AT 2 ϩ/ϩ mice. L-NAME decreased RBF in these mice further from 4.08 Ϯ 0.43 to 2.79 Ϯ 0.15 ml/min per g of kidney wt. GFR was not significantly different between AT 2 ϩ/ϩ and AT 2 Ϫ/Ϫ mice (1.09 Ϯ 0.08 versus 1.21 Ϯ 0.09 ml/min per g of kidney wt). L-NAME reduced GFR in AT 2 Ϫ/Ϫ to 0.87 Ϯ 0.07 ml/min per g of kidney wt. Fractional sodium (FE Na ) and water (FE H2O ) curves were shifted more strongly to the right by L-NAME in AT 2 Ϫ/Ϫ mice than in AT 2 ϩ/ϩ mice. AT 1 receptor blocker treatment lowered BP in both L-NAME-treated strains to basal values. It is concluded that the AT 1 receptor plays a key role in the impaired renal sodium and water excretion induced by NO synthesis blockade. Changes in RBF, GFR, and tubular sodium and water reabsorption are involved and may be also responsible for the greater BP increase in L-NAME-treated AT 2 Ϫ/Ϫ mice.Nitric oxide (NO) and angiotensin II (AngII) are integrated in homeostatic mechanisms regulating renal function and BP. The effects of AngII are mediated by at least two receptor isoforms (AT 1 and AT 2 ). AngII stimulates proximal tubular sodium reabsorption and decreases sodium excretion by reducing renal medullary blood flow via the AT 1 receptor. AngII also enhances sodium reabsorption indirectly by stimulating aldosterone release through the AT 1 receptor. There is evidence that the AT 2 receptor serves a counter-regulatory protective role (1). Tonically secreted intrarenal NO is also involved in the control of glomerular hemodynamics, tubuloglomerular feedback, renin release, and sodium and water excretion (2). NOsynthesis blockade by L-NAME lowers renal blood flow, reduces sodium and water excretion, shifts pressure-natriuresis curves toward the right (2-5), and increases BP (6 -8). The renin-angiotensin system participates in the renal and systemic alterations induced by NO synthesis blockade (9). Chronic AT 1 receptor or converting enzyme blockade prevents the development of L-NAME hypertension (6,10). However, pretreatment with losartan had no effect on the impaired pressure natriuresis produced by NO-synthesis blockade in another study (11), suggesting that the AT 1 receptor may not or only partially be involved in L-NAME-induced changes. This suggestion is underscored by results suggesting that AT 2 receptor ...

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Section: Discussionmentioning

confidence: 99%

Pressure Natriuresis in AT2 Receptor–Deficient Mice with L-NAME Hypertension

Obst¹,

Groß²,

Janke

et al. 2003

Journal of the American Society of Nephrology

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“…Many regional perfusion studies have been performed in animals that have had optical fibers acutely or chronically implanted into the renal parenchyma (2, 17, 28-30, 70, 73, 76). Studies of the extent of autoregulation of medullary perfusion with variation in renal perfusion pressure have produced variable results (17, 70,76,90), but much evidence points to a possible role for variation of medullary autoregulation with extracellular fluid volume status to regulate "pressure natriuresis" (17, 76,78,131). Laser-Doppler studies with implanted flow probes yield a signal from a fixed volume of tissue and thus the probes are sensitive to probe orientation.…”

Section: Role Of Dvr In Regulation Of Medullary Blood Flowmentioning

confidence: 99%

“…Global inhibition of NOS1, NOS2, and NOS3 isoforms with nonselective blockers decreases medullary NO levels and induces salt retention and hypertension. In addition, global NOS inhibition reduces medullary blood flow and tissue oxygenation (11,42,78,124). NO generation may be important to abrogate tissue hypoxia that would otherwise arise from release of vasoconstrictors.…”

Section: Medullary Po2 and Perfusion Of The Medullamentioning

confidence: 99%

Physiology of the renal medullary microcirculation

Pallone

Zhang

Rhinehart

2003

American Journal of Physiology-Renal Physiology

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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“…On the one hand, NOS inhibition decreases renal blood flow,4 thus oxygen delivery. In particular, NO is responsible for medullary flow 6. The majority of renal NOS activity is located in the medulla 7.…”

Section: Introductionmentioning

confidence: 99%

Nitric Oxide Synthase Inhibition Induces Renal Medullary Hypoxia in Conscious Rats

Emans

Janssen

Joles

et al. 2018

JAHA

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BackgroundRenal hypoxia, implicated as crucial factor in onset and progression of chronic kidney disease, may be attributed to reduced nitric oxide because nitric oxide dilates vasculature and inhibits mitochondrial oxygen consumption. We hypothesized that chronic nitric oxide synthase inhibition would induce renal hypoxia.Methods and ResultsOxygen‐sensitive electrodes, attached to telemeters, were implanted in either renal cortex (n=6) or medulla (n=7) in rats. After recovery and stabilization, baseline oxygenation (pO 2) was recorded for 1 week. To inhibit nitric oxide synthase, N‐ω‐nitro‐l‐arginine (L‐NNA; 40 mg/kg/day) was administered via drinking water for 2 weeks. A separate group (n=8), instrumented with blood pressure telemeters, followed the same protocol. L‐NNA rapidly induced hypertension (165±6 versus 108±3 mm Hg; P<0.001) and proteinuria (79±12 versus 17±2 mg/day; P<0.001). Cortical pO 2, after initially dipping, returned to baseline and then increased. Medullary pO 2 decreased progressively (up to −19±6% versus baseline; P<0.05). After 14 days of L‐NNA, amplitude of diurnal medullary pO 2 was decreased (3.7 [2.2–5.3] versus 7.9 [7.5–8.4]; P<0.01), whereas amplitudes of blood pressure and cortical pO 2 were unaltered. Terminal glomerular filtration rate (1374±74 versus 2098±122 μL/min), renal blood flow (5014±336 versus 9966±905 μL/min), and sodium reabsorption efficiency (13.0±0.8 versus 22.8±1.7 μmol/μmol) decreased (all P<0.001).ConclusionsFor the first time, we show temporal development of renal cortical and medullary oxygenation during chronic nitric oxide synthase inhibition in unrestrained conscious rats. Whereas cortical pO 2 shows transient changes, medullary pO 2 decreased progressively. Chronic L‐NNA leads to decreased renal perfusion and sodium reabsorption efficiency, resulting in progressive medullary hypoxia, suggesting that juxtamedullary nephrons are potentially vulnerable to prolonged nitric oxide depletion.

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Role of nitric oxide in renal papillary blood flow and sodium excretion.

Cited by 199 publications

References 13 publications

Pressure Natriuresis in AT2 Receptor–Deficient Mice with L-NAME Hypertension

Pressure Natriuresis in AT2 Receptor–Deficient Mice with L-NAME Hypertension

Physiology of the renal medullary microcirculation

Nitric Oxide Synthase Inhibition Induces Renal Medullary Hypoxia in Conscious Rats

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