Inhibition of intrarenal NO stimulates renin secretion through a macula densa-mediated mechanism

Schnackenberg, Christine G.; Tabor, Barbara; Strong, Molly; Granger, Joey P.

doi:10.1152/ajpregu.1997.272.3.r879

Cited by 27 publications

(27 citation statements)

References 16 publications

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“…The NO-induced reduction in renal vascular tone is attributable in part to dilation of the afferent arteriole. In addition to increasing the glomerular filtration rate (GFR) modulates renin secretion via the juxtaglomerular apparatus and tubuloglomerular feedback (38)(39)(40)(41). However, as observed in our study and others, NO also regulates transporters in various nephron segments (9,26).…”

Section: Discussionsupporting

confidence: 65%

Hemodynamic Parameters During Normal and Hypertensive Pregnancy in Rats: Evaluation of Renal Salt and Water Transporters

Tardin

Boim

et al. 2008

Hypertension in Pregnancy

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Section: Discussionsupporting

confidence: 65%

Hemodynamic Parameters During Normal and Hypertensive Pregnancy in Rats: Evaluation of Renal Salt and Water Transporters

Tardin

Boim

et al. 2008

Hypertension in Pregnancy

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“…The current study cannot differentiate whether the increase in the activity of the RAS is directly linked to decreased AT 2 receptor activity or is directly linked to reduction in its mediator NO and cGMP. The influence of NO is controversial, with studies showing stimulation, 34,35 inhibition, 36 or no direct influence 37-39 on renin production. Cyclic GMP has been shown to inhibit renin expression and secretion.…”

Section: Discussionmentioning

confidence: 99%

Angiotensin Subtype-2 Receptors Inhibit Renin Biosynthesis and Angiotensin II Formation

et al. 2005

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Abstract-Renin is regulated by angiotensin subtype 1 (AT 1 ) receptor, but it is unknown whether angiotensin subtype 2 (AT 2 ) receptor contributes to this regulation. We hypothesized that AT 2 receptors inhibit angiotensin II (Ang II) through inhibition of renin biosynthesis. We monitored changes in renal Ang II, renin mRNA and protein expression, and plasma renin concentration (PRC) in response to renal cortical administration of the AT 1 receptor blocker valsartan or the AT 2 receptor blocker PD 123319 (PD) in conscious rats administered low sodium intake (LS (Ang II) is the major effector hormone of the renin-angiotensin system (RAS). Most of the known physiological functions and pathologic effects associated with Ang II are mediated by the angiotensin subtype 1 (AT 1 ) receptor, including renin inhibition. 1 In contrast, the functions of the angiotensin subtype 2 (AT 2 ) receptor are still being elucidated. The AT 2 receptor is expressed abundantly during fetal development and declines after birth. [1][2][3] In mammalian adults, the AT 2 receptor had been reported in multiple organs, including the kidney. 4 -6 Currently, the AT 2 receptor has several described functions related to inhibition of cell growth, promotion of cell differentiation, and stimulation of apoptosis. [7][8][9][10][11][12] Previously, we demonstrated that during sodium depletion, the AT 2 receptor mediates renal production of bradykinin, nitric oxide (NO), and cGMP. [13][14][15][16][17] Unlike the well-known effect of AT 1 receptor on renin production, 18 -19 the influence of the AT 2 receptor on renal renin biosynthesis and Ang II production is not known.In this study, we tested the hypothesis that the AT 2 receptor inhibits renal renin synthesis and Ang II production. We used multiple techniques including renal interstitial microdialysis, [13][14][15][16][17] real-time quantitative reverse-transcription polymerase chain reaction, immunohistochemistry, and enzymelinked immunoassays for monitoring changes in renal Ang II, renin mRNA, renin protein expression, and plasma renin concentration to investigate whether intrarenal AT 2 receptors regulate renin production and Ang II formation. We monitored renal interstitial levels of Ang II in conscious rats during sodium restriction, a condition known to increase AT 2 receptor expression, and during AT 1 and AT 2 receptor blockade. 5 A distinct advantage of the microdialysis technique 13 is the ability to monitor renal Ang II levels in conscious rats without undesirable hemodynamic changes. In this study, we demonstrate for the first time to our knowledge that AT 2 receptors regulate the activity of the RAS through inhibition of renin biosynthesis in young rats. Methods Renal Microdialysis TechniqueFor the determination of renal interstitial fluid (RIF) Ang II, we constructed a microdialysis probe as previously described. [13][14][15][16][17] In vitro, best recovery for Ang II was observed with a perfusion rate of 3 L/min, and was Ϸ53%. Animal PreparationThe experiments were approved by the U...

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“…16 It also increases glomerular filtration rate. 11 NO modulates renin secretion by the juxtaglomerular apparatus 15 and tubuloglomerular feedback. 3 Finally, NO regulates transport in various nephron segments as reviewed recently by Ortiz and Garvin.…”

Section: Roles For Renal Nomentioning

confidence: 99%

“…These include increasing renal blood flow caused by vasodilatation, 10 increasing glomerular filtration, 11 inhibiting sodium transport along the nephron, [12][13][14] and regulating release of renin. 15 NO produced by each of the 3 nitric oxide synthases (NOS), NOS 1, NOS 2, and NOS 3, reportedly contributes to the regulation of renal function. Inhibition of NOS activity within the kidney is known to lead to sodium retention and hypertension.…”

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confidence: 99%

Recent Advances in the Regulation of Nitric Oxide in the Kidney

Herrera

Garvin

2005

Hypertension

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Abstract-Nitric oxide (NO) plays important roles in the regulation of renal function and the long-term control of blood pressure. New roles of NO have been proposed recently in diabetes, nephrotoxicity, and pregnancy. NO derived from all 3 NOS isoforms contributes to the overall regulation of kidney function, and recent advances in our understanding of their regulation have been made lately. In this regard, substrate and cofactor availability play important roles in regulating nitric oxide synthase (NOS) activity not only by limiting enzyme activity but also by influencing the coupling of NOS with its cofactors, tetrahydrobiopterin and NADPH. Protein-protein interactions are now recognized to be important negative and positive regulators of NOS. Phosphorylation is another component of the mechanism whereby NOS is activated or deactivated. Increased NOS expression can also influence enzyme activity; however, the degree of expression does not always correlate with enzyme activity because increased NO levels can result in inhibition of NOS. Finally, other potential regulators of NOS such as endogenous L-arginine analogs may also be important. In this article, we summarize recent advances in the regulation of activity and expression of the NOS isoforms within the kidney. renal function and long-term regulation of blood pressure. [1][2][3][4] This is best evidenced by the fact that inhibiting intrarenal NO production increased blood pressure. 5 In addition, reduced NO has been identified as a common denominator of many hypertensive models. 6 -9 The effects of NO on blood pressure via actions in the kidney occur through multiple mechanisms. These include increasing renal blood flow caused by vasodilatation, 10 increasing glomerular filtration, 11 inhibiting sodium transport along the nephron, 12-14 and regulating release of renin. 15 NO produced by each of the 3 nitric oxide synthases (NOS), NOS 1, NOS 2, and NOS 3, reportedly contributes to the regulation of renal function. Inhibition of NOS activity within the kidney is known to lead to sodium retention and hypertension. This review addresses recent advances in our understanding of the role played by renal NO in various physiological and pathophysiological conditions, as well as how NO production is regulated. Roles for Renal NOHistorically, NO produced by the kidney has been thought of primarily as a factor that regulates urinary volume and sodium excretion. The physiological effects of NO can be mediated via changes in renal hemodynamics and/or salt and water absorption by the nephron. NO reduces renal vascular tone in part by dilating the afferent arteriole. 16 It also increases glomerular filtration rate. 11 NO modulates renin secretion by the juxtaglomerular apparatus 15 and tubuloglomerular feedback. 3 Finally, NO regulates transport in various nephron segments as reviewed recently by Ortiz and Garvin. 12 More recently it has been recognized that in a number of pathophysiological conditions, the actions of NO on renal hemodynamics and/or nephron transport are ...

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Inhibition of intrarenal NO stimulates renin secretion through a macula densa-mediated mechanism

Cited by 27 publications

References 16 publications

Hemodynamic Parameters During Normal and Hypertensive Pregnancy in Rats: Evaluation of Renal Salt and Water Transporters

Hemodynamic Parameters During Normal and Hypertensive Pregnancy in Rats: Evaluation of Renal Salt and Water Transporters

Angiotensin Subtype-2 Receptors Inhibit Renin Biosynthesis and Angiotensin II Formation

Recent Advances in the Regulation of Nitric Oxide in the Kidney

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