Nitric oxide and renal nerve-mediated proximal tubular reabsorption in normotensive and hypertensive rats

Wu, Xiao Chun; Harris, Peter; Johns, Edward J.

doi:10.1152/ajprenal.1999.277.4.f560

Cited by 34 publications

(54 citation statements)

References 23 publications

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“…Thus ANG II stimulates neuronal NOS and renal interstitial cGMP production, probably via the AT 2 receptor (52), and recent work by Zhang and Mayeux (65) shows that neuronal NOS-derived NO is triggered beyond a certain ANG II threshold concentration, thereby counteracting the stimulatory effect on the Na-K-ATPase. Similarly, studies have shown that NO exerts a tonic inhibitory action on nervemediated proximal tubular reabsorption, and at the same time NO exerts a facilitatory role in norepinephrine release (55,61,62). Altogether these experiments show that NO is an integrated modulating agent in renal proximal tubular function, further studies on the interaction between the NO system and other modulators of proximal tubular sodium handling in cirrhosis are warranted.…”

Section: Discussionmentioning

confidence: 76%

“…These transporters are responsible for the majority of transepithelial sodium reabsorption in the proximal tubules (1,5,45,57). Micropuncture studies in rats have shown that sodium nitroprusside added to the tubular perfusate significantly decreases proximal tubular fluid reabsorption (14,61), and studies in humans have shown that systemic administration of NOS inhibitors have antinatriuretic effects associated with marked decreases in FE Li (4,6,36). These in vitro and in vivo experiments suggest that NO exerts a tonic inhibitory effect on proximal tubular sodium reabsorption.…”

Section: Discussionmentioning

confidence: 92%

“…However, besides the circulatory effects, NO also exerts direct effects on renal tubular function, including an inhibitory action on proximal tubular sodium handling. Excess NO has been shown to inhibit the Na-K-ATPase and the type 3 sodium/proton exchanger (NHE3) in proximal tubular cell lines (20,33,46), and micropuncture studies in rats have shown that NO significantly decreases proximal tubular fluid reabsorption (14,61). These micropuncture data from rats are supported by studies in humans showing that systemic administration of NOS inhibitors decreases fractional excretion of sodium (FE Na ) and fractional excretion of lithium (FE Li ; an index for the delivery of tubular fluid out of the proximal tubules) (4,6,36).…”

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confidence: 99%

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Chronic nitric oxide synthase inhibition exacerbates renal dysfunction in cirrhotic rats

Græbe¹,

Brønd²,

Christensen³

et al. 2004

American Journal of Physiology-Renal Physiology

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Graebe, Martin, Lone Brønd, Sten Christensen, Søren Nielsen, Niels V. Olsen, and Thomas E. N. Jonassen. Chronic nitric oxide synthase inhibition exacerbates renal dysfunction in cirrhotic rats. Am J Physiol Renal Physiol 286: F288-F297, 2004. First published October 28, 2003 10.1152/ajprenal.00089.2003.-The present study investigated sodium balance and renal tubular function in cirrhotic rats with chronic blockade of the nitric oxide (NO) system. Rats were treated with the nonselective NO synthase inhibitor N G -nitro-L-arginine methyl ester (L-NAME) starting on the day of common bile duct ligation (CBL). Three weeks of daily sodium balance studies showed that CBL rats developed sodium retention compared with shamoperated rats and that L-NAME treatment dose dependently deteriorated cumulative sodium balance by reducing urinary sodium excretion. Five weeks after CBL, renal clearance studies were performed, followed by Western blotting of the electroneutral type 3 sodium/ proton exchanger (NHE3) and the Na-K-ATPase present in proximal tubules. Untreated CBL rats showed a decreased proximal reabsorption with a concomitant reduction of NHE3 and Na-K-ATPase levels, indicating that tubular segments distal to the proximal tubules were responsible for the increased sodium reabsorption. L-NAME-treated CBL rats showed an increased proximal reabsorption measured by the lithium clearance method and showed a marked increase in NHE3 and Na-K-ATPase protein levels. Our results show that chronic L-NAME treatment exacerbates the sodium retention found in CBL rats by a significant increase in proximal tubular reabsorption. common bile duct ligation; type 3 sodium/proton exhanger; proximal tubular function; lithium clearance THE EARLY STATE OF COMPENSATED cirrhosis is associated with renal sodium and water retention combined with a hyperdynamic circulation, evident as systemic arterial vasodilation with decreased total peripheral resistance and increased cardiac output. In 1991, Vallance and Moncada (56) suggested that increased systemic nitric oxide (NO) formation induced by low-grade endotoxemia could be the mediator of the hyperdynamic circulation. Since then, several studies in both animals and humans have validated this hypothesis and increased NO synthesis is now believed to be one of the early pathophysiological mechanisms of cirrhosis, being essential for systemic arterial vasodilation (3,7,19,24,37,38).The peripheral arterial vasodilation theory stated by Schrier and co-workers (49) proposes that the vasodilation-mediated relative vascular underfilling in cirrhosis is the primary event responsible for the renal sodium and water retention via activation of baroreceptors and humoral antinatriuretic mechanisms. Normalization of the hyperdynamic circulation by blockade of NO synthase (NOS) would in this context be a straightforward approach to try to prevent the sodium retention in cirrhotic liver disease, and a few studies have shown that short-term NOS inhibition in cirrhotic rats actually ameliorates the impaired sodium e...

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Section: Discussionmentioning

confidence: 76%

Section: Discussionmentioning

confidence: 92%

mentioning

confidence: 99%

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Chronic nitric oxide synthase inhibition exacerbates renal dysfunction in cirrhotic rats

Græbe¹,

Brønd²,

Christensen³

et al. 2004

American Journal of Physiology-Renal Physiology

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“…1,8,[21][22][23] Reduced renal excretory function in denervated kidneys may result from the diminished actions of several natriuretic agents, including NO and endothelin. 24,25 Another possibility is that this relative impairment in sodium excretion in denervated kidneys may reflect renal denervation supersensitivity, which may have diminished functional significance during prolonged activation of the baroreflex.…”

Section: Discussionmentioning

confidence: 99%

Renal Denervation Does Not Abolish Sustained Baroreflex-Mediated Reductions in Arterial Pressure

Lohmeier

Hildebrandt²,

Dwyer³

et al. 2007

Hypertension

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Abstract-Recent studies indicate that suppression of renal sympathetic nerve activity and attendant increments in renal excretory function are sustained baroreflex-mediated responses in hypertensive animals. Given the central role of the kidneys in long-term regulation of arterial pressure, we hypothesized that the chronic blood pressure-lowering effects of the baroreflex are critically dependent on intact renal innervation. This hypothesis was tested in 6 dogs by bilaterally activating the carotid baroreflex electrically for 7 days before and after bilateral renal denervation. Before renal denervation, control values for mean arterial pressure and plasma norepinephrine concentration were 95Ϯ2 mm Hg and 96Ϯ12 pg/mL, respectively. During day 1 of baroreflex activation, mean arterial pressure decreased 13Ϯ1 mm Hg, and there was modest sodium retention. Daily sodium balance was subsequently restored, but reductions in mean arterial pressure were sustained throughout the 7 days of baroreflex activation. Activation of the baroreflex was associated with sustained decreases in plasma norepinephrine concentration (Ϸ50%) and plasma renin activity (30% to 40%). All of the values returned to control levels during a 7-day recovery period. Two weeks after renal denervation, control values for mean arterial pressure, plasma norepinephrine concentration, plasma renin activity, and sodium excretion were comparable to those measured when the renal nerves were intact. Moreover, after renal denervation, all of the responses to activation of the baroreflex were similar to those observed before renal denervation. These findings demonstrate that the presence of the renal nerves is not an obligate requirement for achieving long-term reductions in arterial pressure during prolonged activation of the baroreflex. Key Words: baroreflex Ⅲ arterial pressure Ⅲ renal nerves Ⅲ sympathetic nervous system Ⅲ norepinephrine Ⅲ renin-angiotensin system Ⅲ sodium excretion N ovel experimental approaches in chronically instrumented animals have recently provided greater insight into the role of baroreflexes in long-term control of arterial pressure. 1-10 These studies, conducted over several weeks, indicate that baroreflex resetting is incomplete in experimental models of hypertension. They also indicate that during chronic increases in arterial pressure, there is sustained baroreflex-mediated suppression of renal sympathetic nerve activity and attendant increments in renal excretory function, responses expected to attenuate the severity of hypertension. However, the quantitative importance of renal sympathoinhibition in mediating the chronic blood pressure-lowering effects of sustained baroreflex activation remains unclear.We have recently developed methodology that is ideal for evaluating the time dependency and underlying mechanisms of the blood pressure-lowering effects of the baroreflex. 6,10 To activate the carotid baroreflex, an externally adjustable pulse generator is used to electrically stimulate electrodes chronically implanted around both c...

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“…Furthermore, we tested for differential expression of cyclooxygenase 2 (COX-2), endothelial nitric oxide synthase (NOS), and neuronal NOS. Altered renal expression and function of these enzymes or decreased renal availability of their products is involved in the pathogenesis of experimental hypertension (9,23,39,41,44). COX-2 expression is developmentally regulated in rat kidneys (45), and renal neuronal NOS expression and function depend on renal innervation (16,41).…”

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confidence: 99%

Neonatal sympathectomy reduces NADPH oxidase activity and vascular resistance in spontaneously hypertensive rat kidneys

Schlüter

Grimm²,

Steinbach³

et al. 2006

American Journal of Physiology-Regulatory, Integrative and Comp

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(SHR). In SHR transplanted with a kidney from sympathectomized SHR, arterial pressure was lower and less Na ϩ sensitive than in SHR transplanted with a kidney from hydralazine-treated SHR. This study was performed to identify underlying renal mechanisms. Tests for differential renal mRNA expression of nine a priori selected genes revealed robust differences for renal medullary expression of the NADPH oxidase subunit p47phox . Therefore, we investigated the effects of neonatal sympathectomy on renal mRNA expression of NADPH oxidase subunits, NADPH oxidase activity, and renal function. In 10-wk-old sympathectomized SHR fed a 0.6% NaCl diet, medullary p47 phox and gp91 phox expression was 40% less than in hydralazine-treated SHR. Also, after a 1.8% NaCl diet, medullary p47 phox mRNA expression was lower in sympathectomized than in hydralazine-treated SHR. We found lower cortical (Ϫ30%, P Ͻ 0.01) and medullary (Ϫ30%, P Ͻ 0.05) NADPH oxidase activities in sympathectomized than in hydralazine-treated or untreated SHR. Glomerular filtration rate, renal blood flow, medullary blood flow, and fractional Na ϩ excretion in kidney grafts from sympathectomized and hydralazine-treated donors (n ϭ 8 per group) were similar at baseline and in response to a 20-mmHg rise in renal perfusion pressure. Renal vascular resistance was lower in kidneys from sympathectomized than hydralazine-treated donors (25 Ϯ 2 vs. 32 Ϯ 4 mmHg ⅐ min ⅐ ml Ϫ1 , P Ͻ 0.05). The results indicate that the sympathetic nervous system contributes to the level of renal NADPH oxidase activity and to perinatal programming of alterations in renal vascular function that lead to elevated renal vascular resistance in SHR. inbred strains; kidney; sympathetic activity; gene expression THE KIDNEY AND THE SYMPATHETIC nervous system contribute to the pathogenesis of arterial hypertension in spontaneously hypertensive rats (SHR) (12). Arterial pressure can be chronically lowered in SHR by neonatal sympathectomy (19,21), and renal mechanisms are involved in this chronic arterial pressure reduction (14). We previously showed lower arterial pressure in SHR transplanted with a kidney from a sympathectomized SHR donor than in SHR recipients of a kidney from a hydralazine-treated SHR donor (14). In addition, Na ϩ sensitivity of arterial pressure was lower in recipients of a kidney graft from sympathectomized donors than in recipients of a graft from hydralazine-treated donors (14). The present study was performed to identify mechanisms that may explain these findings; therefore, we focused on kidneys from sympathectomized and hydralazine-treated SHR. Limited data are available on chronic effects of neonatal sympathectomy on SHR kidneys. Thus we initially tested for differential mRNA expression of nine a priori selected genes in kidneys from sympathectomized and hydralazine-treated SHR exposed to three different experimental conditions. Our aim was to identify alterations in gene expression that persist under different conditions and, therefore, may be involved in chronic effects...

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Nitric oxide and renal nerve-mediated proximal tubular reabsorption in normotensive and hypertensive rats

Cited by 34 publications

References 23 publications

Chronic nitric oxide synthase inhibition exacerbates renal dysfunction in cirrhotic rats

Chronic nitric oxide synthase inhibition exacerbates renal dysfunction in cirrhotic rats

Renal Denervation Does Not Abolish Sustained Baroreflex-Mediated Reductions in Arterial Pressure

Neonatal sympathectomy reduces NADPH oxidase activity and vascular resistance in spontaneously hypertensive rat kidneys

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