Basal nitric oxide production curtails arteriolar vasoconstrictor responses to ANG II in rat kidney

Ikenaga, Hideki; Fallet, Rachel W.; Carmines, Pamela K.

doi:10.1152/ajprenal.1996.271.2.f365

Cited by 30 publications

(36 citation statements)

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“…These observations were consistent with the direct observations that AVP stimulated NO production in the epithelial cells of inner medullary collecting ducts (IMCD) as determined by fluorescent microscopy (67) and other reports that AVP stimulated increases of urinary cGMP concentrations (103) and that the inhibition of NOS acutely enhanced systemic pressor responses to AVP (35,109).…”

Section: Acute Counterregulatory Action Of Renal Medullary No On Circsupporting

confidence: 91%

“…Reduction of tissue NO production with NOS inhibition was found by some investigators to enhance ANG II-induced reduction of renal blood flow (1) and to potentiate the vasoconstrictor effects of ANG II in isolated perfused kidneys (105). Similar findings were obtained using the in vitro perfused juxtamedullary preparation (35) and in isolated perfused afferent arterioles (37). Others found no evidence of enhanced vasoconstriction to either ANG II or NE after NOS inhibition using a perfused split kidney juxtamedullary preparation when vessel diameter was restored to normal by sodium nitroprusside (35), or in studies using an in vitro hydronephrotic kidney preparation (87).…”

Section: Acute Counterregulatory Action Of Renal Medullary No On Circmentioning

confidence: 56%

“…Several studies found that NE can induce NO release through the ␣ 2 -receptors (35,68,135). ␣ 2 -Activation appears to increase the influence of NO in the glomeruli and proximal tubules of rats (130), and it has been shown that the vasculature becomes more sensitive to ␣ 2 -receptor stimulation with chronic NOS inhibition (31).…”

Section: Acute Counterregulatory Action Of Renal Medullary No On Circmentioning

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

176

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: Acute Counterregulatory Action Of Renal Medullary No On Circsupporting

confidence: 91%

Section: Acute Counterregulatory Action Of Renal Medullary No On Circmentioning

confidence: 56%

Section: Acute Counterregulatory Action Of Renal Medullary No On Circmentioning

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

176

202

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“…Comparing S1P with many other common vasoconstrictors on afferent arteriolar reactivity shows that the S1P-mediated vasoconstriction of afferent arterioles is less potent than the vasoconstriction induced by endothelin 1, 47 but similar to the vasoconstriction induced by other GPCR agonists, such as angiotensin II, 35,48 arginine vasopressin, 48 and NE, 35 whereas S1P is more potent than ATP. 49 It requires approximately 10 pM of endothelin-1, 6 nM of angiotensin II, 70 nM of S1P, 200 nM of arginine vasopressin, 300 nM of NE, and 100 mM of ATP to achieve a 25% reduction of afferent arteriolar diameters.…”

Section: Discussionmentioning

confidence: 96%

Sphingosine-1-Phosphate Evokes Unique Segment-Specific Vasoconstriction of the Renal Microvasculature

Guan¹,

Singletary²,

Cook³

et al. 2014

Journal of the American Society of Nephrology

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Sphingosine-1-phosphate (S1P), a bioactive sphingolipid metabolite, has been implicated in regulating vascular tone and participating in chronic and acute kidney injury. However, little is known about the role of S1P in the renal microcirculation. Here, we directly assessed the vasoresponsiveness of preglomerular and postglomerular microvascular segments to exogenous S1P using the in vitro blood-perfused juxtamedullary nephron preparation. Superfusion of S1P (0.001-10 mM) evoked concentration-dependent vasoconstriction in preglomerular microvessels, predominantly afferent arterioles. After administration of 10 mM S1P, the diameter of afferent arterioles decreased to 35%65% of the control diameter, whereas the diameters of interlobular and arcuate arteries declined to 50%612% and 68%66% of the control diameter, respectively. Notably, efferent arterioles did not respond to S1P. The S1P receptor agonists FTY720 and FTY720-phosphate and the specific S1P1 receptor agonist SEW2871 each evoked modest afferent arteriolar vasoconstriction. Conversely, S1P2 receptor inhibition with JTE-013 significantly attenuated S1P-mediated afferent arteriolar vasoconstriction. Moreover, blockade of L-type voltage-dependent calcium channels with diltiazem or nifedipine attenuated S1P-mediated vasoconstriction. Intravenous injection of S1P in anesthetized rats reduced renal blood flow dose dependently. Western blotting and immunofluorescence revealed S1P1 and S1P2 receptor expression in isolated preglomerular microvessels and microvascular smooth muscle cells. These data demonstrate that S1P evokes segmentally distinct preglomerular vasoconstriction via activation of S1P1 and/or S1P2 receptors, partially via L-type voltagedependent calcium channels. Accordingly, S1P may have a novel function in regulating afferent arteriolar resistance under physiologic conditions. 25: 177425: -178525: , 201425: . doi: 10.1681 Sphingosine 1-phosphate (S1P) is recognized as an important signaling molecule in diverse biologic processes. 1,2 Growing evidence indicates that S1P plays an important role in regulating vascular reactivity. 3-5 S1P is a bioactive sphingolipid metabolite and is released from erythrocytes, platelets, and endothelial cells. 6,7 The majority of S1P effects are mediated via five distinct receptors (S1P1-S1P5 receptors), which represent a family of small G proteincoupled receptors (GPCRs) 5 ; however, S1P can also exist in the cytoplasm as a second messenger involved in Ca 2+ mobilization or cell survival and proliferation. 8,9 S1P1-S1P3 receptors are expressed by a wide variety of tissues, whereas S1P4 and S1P5 receptors are mainly expressed in cells of the immune and nervous systems. 4,10 In the vasculature, endothelial cells mainly express S1P1 and S1P3 with variable expression of S1P2, whereas vascular smooth muscle cells express S1P2 and S1P3 with variable expression of S1P1. [3][4][5] Studies in animals show that application of exogenous S1P J Am Soc Nephrol

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“…10 Short-term studies by others also support the conclusions that Ang II releases NO and that inhibition of NOS activity enhances the renal vasoconstrictor actions of Ang II in rat kidneys. 23 Ang II infusion has been reported to elevate renal excretion of nitrate and/or nitrite 14 and increase cGMP concentration in renal cortical interstitial fluid. 13 Madrid et al 24 have shown that renal NO production buffers Ang II effects on pressure-natriuresis and on the CBF and papillary blood flow.…”

Section: Initial Responses To Intravenous Ang II Infusionmentioning

confidence: 99%

Local Renal Medullary L-NAME Infusion Enhances the Effect of Long-Term Angiotensin II Treatment

1999

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Abstract-We hypothesized that the relatively high doses of angiotensin (Ang) II required to produce hypertension in rats were related to stimulation of renal medullary nitric oxide production, which in turn blunted reductions in medullary blood flow and the development of hypertension. Ang II was infused (5 days at 3 ng ⅐ kg Ϫ1 ⅐ min Ϫ1 IV) to uninephrectomized Sprague-Dawley rats in the presence and absence of a continuous medullary interstitial N G -nitro-L-arginine methyl ester (L-NAME) infusion. Renal cortical and medullary blood flows were determined with the use of implanted optical fibers and laser-Doppler flowmetry. Ang II in the absence of medullary nitric oxide synthase inhibition did not change cortical or medullary blood flow or mean arterial pressure. A threshold dose of L-NAME was determined (75 g ⅐ kg Ϫ1 ⅐ h Ϫ1 ) that did not produce significant short-or long-term changes in medullary blood flow and mean arterial pressure. In rats with blunted medullary nitric oxide synthase activity, Ang II infused intravenously resulted in a 30% reduction in medullary blood flow (from 1.3 to 0.9Ϯ0.2V) and Ϸ20 mm Hg increase in mean arterial pressure with Ang II infusion over 5 days. During 70 minutes after the start of intravenous Ang II, there was an immediate reduction in medullary blood flow, with no changes in cortical blood flow or mean arterial pressure. We conclude that the relative insensitivity of rats to long-term elevations of circulating Ang II is due to the potent counterregulatory actions of the nitric oxide system, specifically within the renal medulla. The results provide novel insights of how the organism attempts to protect itself from the hypertensive effects of Ang II. Key Words: hypertension, renal Ⅲ kidney Ⅲ angiotensin II Ⅲ renal blood flow Ⅲ nitric oxide Ⅲ nitric oxide synthase I t is well recognized that elevations of circulating angiotensin (Ang) II cause resetting of the pressure-natriuresis relationship to elevated levels of arterial blood pressure through the renal retention of sodium and volume expansion. 1 Yet considerable species differences have been found in the concentrations of Ang II required to produce chronic hypertension. We have found that Ang II infused long term at concentrations of 3 to 5 ng ⅐ kg Ϫ1 ⅐ min Ϫ1 produce Ϸ30 mm Hg increase in mean arterial pressure (MAP) over a period of 1 week in mongrel dogs maintained on a normal daily NaCl diet. 2 Humans exhibit even greater pressor sensitivity to prolonged infusions of Ang II. 3 In contrast, prolonged infusion of Ang II at 3 to 5 ng ⅐ kg Ϫ1 ⅐ min Ϫ1in Sprague-Dawley rats does not lead to a significant increase in MAP, 4 and investigators generally administer Ang II at rates of 30 to 60 ng ⅐ kg Ϫ1 ⅐ min Ϫ1 to induce prolonged hypertension in rats. 5 A number of studies have demonstrated that the medullary vasculature of Sprague-Dawley rats is relatively refractive to the vasoconstrictor effects of Ang II compared with the cortical circulation. 6,7 Subpressor doses of Ang II administered intravenously that can significan...

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Basal nitric oxide production curtails arteriolar vasoconstrictor responses to ANG II in rat kidney

Cited by 30 publications

References 0 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

Sphingosine-1-Phosphate Evokes Unique Segment-Specific Vasoconstriction of the Renal Microvasculature

Local Renal Medullary L-NAME Infusion Enhances the Effect of Long-Term Angiotensin II Treatment

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