Effect of chronic renal medullary nitric oxide inhibition on blood pressure

Mattson, David L.; Lu, Shanhong; Nakanishi, Kazushige; Papanek, Paula E.; Cowley, Allen W.

doi:10.1152/ajpheart.1994.266.5.h1918

Cited by 123 publications

(135 citation statements)

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“…5, this renal interstitial (ri) infusion of L-NAME resulted in a sustained reduction of renal MBF (ϳ30%) with no measurable changes of cortical flow as determined daily in unanesthetized rats with chronically implanted optical fibers. This reduction of MBF was associated with an immediate reduction of sodium excretion, retention of sodium, and the development of hypertension (59). This demonstrated that reduction of NO production in the medulla alone could reduce MBF and produce hypertension.…”

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

confidence: 83%

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

confidence: 83%

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

View full text Add to dashboard Cite

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“…The rats were uninephrectomized, and a catheter was implanted in the renal medulla as described previously (29,42,47) ϳ2 wk prior to the injection. shRNA plasmids (100 g) were combined with in vivo-jetPEI (PolyPlus, New York, NY) at a ratio of 8 following the manufacturer's instructions and injected into the catheter over 1 min.…”

Section: Methodsmentioning

confidence: 99%

“…Chronic monitoring of arterial blood pressure in freely moving rats using indwelling femoral arterial catheters was performed as described previously (29,42,47).…”

Section: Methodsmentioning

confidence: 99%

Renal medullary 11β-hydroxysteroid dehydrogenase type 1 in Dahl salt-sensitive hypertension

Liu

Singh

Usa

et al. 2008

Physiological Genomics

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Liu Y, Singh RJ, Usa K, Netzel BC, Liang M. Renal medullary 11␤-hydroxysteroid dehydrogenase type 1 in Dahl salt-sensitive hypertension. Physiol Genomics 36: 52-58, 2008. First published September 30, 2008 doi:10.1152/physiolgenomics.90283.2008.-The Dahl salt-sensitive rat is a widely used model of human salt-sensitive forms of hypertension. The kidney plays an important role in the pathogenesis of Dahl salt-sensitive hypertension, but the molecular mechanisms involved remain a subject of intensive investigation. Gene expression profiling studies suggested that 11␤-hydroxysteroid dehydrogenase type 1 might be dysregulated in the renal medulla of Dahl salt-sensitive rats. Additional analysis confirmed that renal medullary expression of 11␤-hydroxysteroid dehydrogenase type 1 was downregulated by a high-salt diet in SS-13 BN rats, a consomic rat strain with reduced blood pressure salt sensitivity, but not in Dahl salt-sensitive rats. 11␤-Hydroxysteroid dehydrogenase type 1 is known to convert inactive 11-dehydrocorticosterone to active corticosterone. The urinary corticosterone/11-dehydrocorticosterone ratio as well as urinary excretion of corticosterone was higher in Dahl salt-sensitive rats than in SS-13 BN rats. Knockdown of renal medullary 11␤-hydroxysteroid dehydrogenase type 1 with small-interfering RNA attenuated the early phase of salt-induced hypertension in Dahl salt-sensitive rats and reduced urinary excretion of corticosterone. Knockdown of 11␤-hydroxysteroid dehydrogenase type 1 did not affect blood pressure in SS-13 BN rats. Long-term attenuation of salt-induced hypertension was achieved with small hairpin RNA targeting renal medullary 11␤-hydroxysteroid dehydrogenase type 1. In summary, we have demonstrated that suppression of 11␤-hydroxysteroid dehydrogenase type 1 expression in the renal medulla attenuates salt-induced hypertension in Dahl salt-sensitive rats.

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“…NO improves medullary blood flow, which is gaining increasing recognition as a key player in sodium balance and bloodpressure regulation (42). Inhibition of NO acutely in the medulla by direct intramedullary injection of L-NAME results in decrease in medullary blood flow, sodium retention, and hypertension (206). Prolonged intravenous perfusion with L-NAME has similar end results (231).…”

Section: Redox Control Of Kidney Functionmentioning

confidence: 99%