Increase in Renal Medullary Nitric Oxide Synthase Activity Protects From Norepinephrine-Induced Hypertension

Szentiványi, Mátyás; Zou, Ai-Ping; Maeda, Celso Y.; Mattson, David L.; Cowley, Allen W.

doi:10.1161/01.hyp.35.1.418

Cited by 37 publications

(27 citation statements)

References 36 publications

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“…7, in rats that received the subpressor chronic medullary infusion of L-NAME, AVP led to a sustained elevation of blood pressure (117). Similar studies were carried out to determine the responses to chronic intravenous infusions of subpressor doses of ANG II (116) and NE (118). Also shown in Fig.…”

Section: Renal Medullary No Protects Against Chronic Ang Ii- Ne- Anmentioning

confidence: 89%

“…A dose of L-NAME (75 g ⅐ kg Ϫ1 ⅐ h Ϫ1 ) was used that did not reduce basal MBF Ͼ5% when administered into the medullary interstitial space chronically for 2 wk (118). The same dose of L-NAME that significantly attenuated acute increases of medullary [NO] produced by intravenous infusions of subpressor amounts of ANG II, NE, and AVP (116)(117)(118). Doses of ANG II (3.0 ng ⅐ kg Ϫ1 ⅐ min Ϫ1 ), NE (0.1 g ⅐ kg Ϫ1 ⅐ min Ϫ1 ), and AVP (2.0 ng ⅐ kg Ϫ1 ⅐ min Ϫ1 ) were determined that when administered intravenously did not result in elevations of mean arterial pressure Ͼ5 mmHg when infused for 5-7 days to normal Sprague-Dawley rats (see Fig.…”

Section: Renal Medullary No Protects Against Chronic Ang Ii- Ne- Anmentioning

confidence: 99%

“…Influence of NO blockade by L-NAME delivered chronically into the renal interstitium on the blood pressure response to vasoconstrictors given intravenously. MAP was normalized to allow comparison between the individual studies using nonpressor doses of ANG II (116), NE (118), and arginine vasopressin (117). F, Saline ri; E, L-NAME ri.…”

Section: Renal Medullary No Protects Against Chronic Ang Ii- Ne- Anmentioning

confidence: 99%

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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

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176

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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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Section: Renal Medullary No Protects Against Chronic Ang Ii- Ne- Anmentioning

confidence: 89%

Section: Renal Medullary No Protects Against Chronic Ang Ii- Ne- Anmentioning

confidence: 99%

Section: Renal Medullary No Protects Against Chronic Ang Ii- Ne- Anmentioning

confidence: 99%

See 1 more Smart Citation

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

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176

202

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“…In that regard, it is known that both angiotensin and increased renal nerve activity stimulate vasodilating prostaglandins (PGI 2 and PGE 2 ) in the kidney (4). Previous studies have shown an upregulation of NO synthase activity with ␣-adrenergic activity (15,17). In concert with these previous results, in the present study, plasma NO levels during endotoxemia were lower in mice with renal denervation.…”

Section: Discussionmentioning

confidence: 99%

Protective effect of renal denervation on normotensive endotoxemia-induced acute renal failure in mice

Wang

Falk

Jittikanont

et al. 2002

American Journal of Physiology-Renal Physiology

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Protective effect of renal denervation on normotensive endotoxemia-induced acute renal failure in mice. Am J Physiol Renal Physiol 283: F583-F587, 2002. First published March 12, 2002 10.1152/ajprenal.00270.2001.-Acute renal failure (ARF) contributes substantially to the high morbidity and mortality observed during endotoxemia. We hypothesized that selective blockade of the renal nerves would be protective against ARF during the early (16 h) stage of endotoxemia [5 mg lipopolysaccharide (LPS)/kg ip in mice]. At 16 h after LPS, there was no change in mean arterial pressure, but plasma epinephrine (4,604 Ϯ 719 vs. 490 Ϯ 152 pg/ml, P Ͻ 0.001), norepinephrine (2,176 Ϯ 306 vs. 1,224 Ϯ 218 pg/ml, P Ͻ 0.05), and plasma renin activity (40 Ϯ 5 vs. 27 Ϯ 2 ng⅐ ml Ϫ1 ⅐ h Ϫ1 , P Ͻ 0.05) were higher in the LPStreated vs. control mice. The high plasma renin activity level decreased to the control level with renal denervation in endotoxemic mice. After intravenous injection of phentolamine (200 g/kg), the decrement in mean arterial pressure was significantly greater in LPS-treated vs. control mice (19.4 Ϯ 3.5 vs. 8.1 Ϯ 1.5 mmHg, P Ͻ 0.01). Sixteen hours after LPS administration, there were significant decreases in glomerular filtration rate (52 Ϯ 18 vs. 212 Ϯ 23 l/min, P Ͻ 0.01) and renal blood flow (0.58 Ϯ 0.08 vs. 0.85 Ϯ 0.06 ml/min, P Ͻ 0.01) in sham-operated mice. The decrement in glomerular filtration rate during endotoxemia was significantly attenuated in mice with denervated kidneys (32 vs. 79%). Moreover, there was no change in renal blood flow during endotoxemia in mice with renal denervation. The present results therefore demonstrate a protective role of renal denervation during normotensive endotoxemia-related ARF in mice, an effect that may be, at least in part, due to a diminished activation of the renin-angiotensin system. glomerular filtration rate; renal blood flow; epinephrine; norepinephrine; sepsis SEPSIS IS THE MOST FREQUENT CAUSE of acute renal failure (ARF) in intensive care units (1, 2, 9). When sepsis is associated with ARF, the mortality may be as high as 80%. The pathogenetic factors responsible for sepsisrelated ARF, however, are incompletely defined. Although ARF may occur with septic shock, it is also clear that sepsis-related ARF can occur in the absence of hypotension (1, 11).In recent studies from our laboratory, a mouse model of endotoxemia-related ARF has been studied. A significant decrease in glomerular filtration rate (GFR) and renal blood flow (RBF) occurs in the absence of a fall in blood pressure (7). We hypothesized that endotoxemia may be associated with normal blood pressure because of activation of the sympathetic nervous system and renin-angiotensin system (RAS), which secondarily causes renal vasoconstriction. The roles of renal nerves and the RAS in this early renal vasoconstriction during endotoxemia, however, have not been investigated. The present investigation was therefore undertaken in a normotensive mouse model of endotoxemia-induced ARF to examine the effect of selective r...

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“…ANG II, norepinephrine, and vasopressin stimulate release of NO in the medulla (121,150,151,181,185). Subpressor infusion of N G -nitro-Larginine methyl ester into the renal interstitium does not affect medullary blood flow or PO 2 but enables otherwise ineffective doses of ANG II (185) norepinephrine (151,181), or vasopressin (150) to induce a fall in these parameters. Taken together, the data support the conclusion that medullary NO production has a tonic effect in maintaining perfusion and protecting the medulla from ischemic injury.…”

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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Increase in Renal Medullary Nitric Oxide Synthase Activity Protects From Norepinephrine-Induced Hypertension

Cited by 37 publications

References 36 publications

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

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

Protective effect of renal denervation on normotensive endotoxemia-induced acute renal failure in mice

Physiology of the renal medullary microcirculation

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