Pressure natriuresis following acute and chronic inhibition of nitric oxide synthase in rats

Guarasci, Gilda; Kline, Robert L.

doi:10.1152/ajpregu.1996.270.2.r469

Cited by 26 publications

(29 citation statements)

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“…Therefore, any changes in kidney function induced by NO-synthase inhibition may be of major importance for the BP increase after L-NAME. Indeed, systemic or local renal inhibition of NOS activity by L-NAME induced sodium retention, a resetting of pressure-natriuresis relationships, and the development of hypertension in numerous earlier studies (4,5,8,12,(23)(24)(25). With telemetric BP measurements, we observed similar or slightly increased basal BP values in AT 2 Ϫ/Ϫ mice compared with AT 2 ϩ/ϩ mice and similar levels of sodium excretion.…”

Section: Discussionsupporting

confidence: 73%

“…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)(3)(4)(5), and increases BP (6 -8). The renin-angiotensin system participates in the renal and systemic alterations induced by NO synthesis blockade (9).…”

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confidence: 99%

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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: Discussionsupporting

confidence: 73%

mentioning

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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“…Other studies have shown responses similar to ours in chronic and acute administration of NOS inhibition on renal hemodynamics 61. Unfortunately, in the absence of telemetric blood flow probes, we were limited to hemodynamic measurements at the end of the experiment.…”

Section: Discussionmentioning

confidence: 69%

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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“…The slope of the pressure-natriuresis relationship has been shown to be reduced with the inhibition of renal NO synthase (NOS) activity (23,28,98). As reviewed recently by Liang and Knox (50) and by Ortiz and Garvin (80), there is evidence that NO reduces sodium reabsorption in all tubular segments, including the proximal tubule (50,80), thick ascending limb (78,79), distal tubules, and cortical collecting ducts (80), although medullary nephron segments and collecting ducts remain to be studied in detail.…”

Section: No Production and The Overall Regulation Of Renal Functionmentioning

confidence: 99%

“…The first evidence that basal NO production played an important role in determining arterial blood pressure arose from observations that chronic oral or intravenous administration of NOS inhibitors such as L-NAME or N G -monomethyl-L-arginine (L-NMMA) produced hypertension (28,32,55,123). It was unclear, however, whether the observed hypertension was primarily a result of generalized systemic vasoconstriction, an effect of NO reduction in brain, or a primary consequence of reduced renal excretory function.…”

Section: Importance Of Medullary No Production In the Long-term Contrmentioning

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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Pressure natriuresis following acute and chronic inhibition of nitric oxide synthase in rats

Cited by 26 publications

References 0 publications

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

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

Nitric Oxide Synthase Inhibition Induces Renal Medullary Hypoxia in Conscious Rats

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

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