Regulation of cyclooxygenase expression in the kidney by dietary salt intake

Yang, Tianxin; Singh, Inderjit; Pham, Hang; Sun, Daqing; Smart, Ann; Schnermann, Jürgen; Briggs, Josephine P.

doi:10.1152/ajprenal.1998.274.3.f481

Cited by 224 publications

(303 citation statements)

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“…8 COX-2 expression in the kidney under basal conditions suggests that COX-2 may have a physiological role. Expression of the COX-2 isoform is increased in the kidney during development, 9,10 adrenalectomy, 11,12 and low-salt diet 13 ; it is decreased by glucocorticoids. 11,12 The kallikrein-kinin system (KKS) 14 contributes to the regulation of renal blood flow and salt and water excretion.…”

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confidence: 99%

“…The renal effects of bradykinin under physiological conditions are mediated by the B2 receptor, whereas the B1 receptor is expressed in pathological states such as inflammation. 15 Activation of the renin-angiotensin and KKS by administration of a low-sodium diet 13 or angiotensinconverting enzyme inhibition 16 -19 increases renal COX-2 expression. The effects of angiotensin II (Ang II) on expression of COX-2 in the TAL segment via activation of Ang II type-1 receptors have been well documented, whereas the effects of bradykinin on renal COX-2 are unknown despite the identification of 〉2 receptors in this nephron segment.…”

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Bradykinin Regulates Cyclooxygenase-2 in Rat Renal Thick Ascending Limb Cells

et al. 2004

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Abstract-Cyclooxygenase-2 (COX-2) is constitutively expressed in a subset of thick ascending limb cells in the cortex and medulla and increases when the renin-angiotensin and kallikrein-kinin systems are activated. Although the contribution of angiotensin II to the regulation of COX-2 is known, the effects of bradykinin on COX-2 expression have not been determined in this nephron segment. We evaluated expression of B2 bradykinin receptors in thick ascending limb cells containing COX-2 and the effect of bradykinin on COX-2 expression in primary cultured medullary thick ascending cells. The presence of B2 receptors was studied in renal sections by immunohistochemistry with antibodies against B2, COX-2, and Tamm-Horsfall glycoprotein. B2 receptors were detected on the apical and basolateral portion of the thick ascending cells. These cells also contained COX-2, suggesting that COX-2 expression may be regulated via B2 receptor. Incubation of cultured medullary thick ascending cells with bradykinin (10 Ϫ7 to 10 Ϫ5 mol/L) induced a significant increase on COX-2 protein expression. Maximal expression of COX-2 was observed 4 hours after exposure to bradykinin (10 Ϫ7 mol/L), effect abolished by a B2 receptor antagonist (HOE-140; 10 Ϫ6 mol/L). Prostaglandin E 2 production increased when these cells were challenged with bradykinin for 4 hours, indicating that COX-2 was enzymatically active. We have demonstrated (1) the presence of B2 receptors in thick ascending limb cells expressing COX-2 and (2) the stimulatory effect of bradykinin on COX-2 protein expression, via B2 receptors, in cultured medullary thick ascending cells. We suggest that bradykinin can affect ion transport in the thick ascending limb via a COX-2-mediated mechanism. Key Words: cyclooxygenase Ⅲ bradykinin Ⅲ immunohistochemistry Ⅲ rats Ⅲ kidney Ⅲ receptors, bradykinin Ⅲ prostaglandins P rostaglandins participate in the regulation of the renal circulation 1 and tubular ion transport as well as renin secretion, the latter via a cyclooxygenase-2 (COX-2)-dependent mechanism. 2,3 The constitutive enzyme cyclooxygenase-1 (COX-1) has been identified in the collecting tubules and the renal vasculature. 4,5 Immunohistochemical localization studies have detected COX-2 in the perimacula densa region and a subset of thick ascending limb (TAL) epithelial cells located in the cortex (cTAL) 6,7 and outer medulla (mTAL) 7 as well as in interstitial medullary cells. 8 COX-2 expression in the kidney under basal conditions suggests that COX-2 may have a physiological role. Expression of the COX-2 isoform is increased in the kidney during development, 9,10 adrenalectomy, 11,12 and low-salt diet 13 ; it is decreased by glucocorticoids. 11,12 The kallikrein-kinin system (KKS) 14 contributes to the regulation of renal blood flow and salt and water excretion. The renal effects of bradykinin under physiological conditions are mediated by the B2 receptor, whereas the B1 receptor is expressed in pathological states such as inflammation. 15 Activation of the renin-angiotensin and KKS ...

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Bradykinin Regulates Cyclooxygenase-2 in Rat Renal Thick Ascending Limb Cells

et al. 2004

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“…Thus, Cox-2 expression in the macula densa and surrounding cells of the cTALH has been reported to be increased by a low-salt diet (14), by inhibition of the renin-angiotensin system (16,17), by renal hypoperfusion (18), or by furosemide treatment (19). A high-salt diet on the other hand has been shown to reduce Cox-2 expression in the kidney cortex (20,21). None of these conditions changed the expression of Cox-1 in the renal cortex (16 -21).…”

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confidence: 99%

Low Tonicity Mediates a Downregulation of Cyclooxygenase-1 Expression by Furosemide in the Rat Renal Papilla

Castrop¹,

Vitzthum²,

Schumacher³

et al. 2002

Journal of the American Society of Nephrology

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Abstract. It is well known that loop diuretics enhance the renal excretion of prostanoids; therefore, this study aimed to characterize the influence of loop diuretics on the intrarenal expression of cyclooxygenases, which are the key enzymes for prostanoid formation. Male Sprague-Dawley rats were infused with furosemide (12 mg/kg per d) for 6 d, and the expression of cyclooxygenase-1 and -2 (Cox-1 and Cox-2) was analyzed in the different kidney zones. Furosemide increased Cox-2 mRNA expression approximately twofold in the cortex, but it left Cox-1 mRNA expression unaltered there. In the outer medulla, furosemide changed neither Cox-1 nor Cox-2 mRNA expression. In the inner medulla, however, furosemide decreased Cox-1 and Cox-2 mRNA levels to approximately 30% and 60% of their control levels, respectively. The downregulation of mRNA was paralleled by a decrease of Cox protein in the collecting ducts and interstitial cells. Moreover, tissue prostaglandin E 2 (PGE 2 ) concentrations in the papilla were markedly decreased by furosemide to about 30% of the control level. Furosemide lowered urine osmolality from 1550 mosmol/kg to 480 mosmol/ kg; therefore, further consideration was given to the influence of tonicity as a possible mediator of the effects of furosemide on the Cox expression. Water loading was therefore used to reduce the medullary tonicity by a second maneuver. Water loading led to a similar reduction in papillary Cox mRNA expression and PGE 2 content like furosemide. To investigate the influence of the osmolarity on the expression of Cox and the production of PGE 2 under defined in vitro conditions, inner medullary collecting duct cells were incubated with culture medium containing graded amounts of NaCl ranging from 200 mmol/L to 600 mmol/L, and Cox-1 and Cox-2 mRNA abundance were determined after 24 h an 48 h. Cox-1 and Cox-2 mRNA abundance changed in parallel with the osmolarity. The data suggest that loop diuretics decrease the expression of cyclooxygenases and consequently tissue PGE 2 concentrations in the kidney inner medulla. This effect could be related to the breakdown of the papillary osmotic gradient induced by loop diuretics.

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“…28 Recent studies have demonstrated that both isoforms are present in the kidney. 29 COX-1 is constitutively expressed in the glomerulus, the thick ascending limb of Henle's loop, and the collecting duct, 30 and is thought to be responsible for continuous generation of prostaglandins that regulate renal hemodynamics and tubular transport. 31 Recent studies showed that PGE 2 EP2 and EP4 receptors are located in both cortical preglomerular resistance vessels and outer medullary vasa recta bundles, 32,33 and PGI 2 IP receptor mRNA has been detected in both Af-Arts and vasa recta.…”

Section: Discussionmentioning

confidence: 99%

Glomerular Cytochrome P-450 and Cyclooxygenase Metabolites Regulate Efferent Arteriole Resistance

et al. 2005

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Abstract-Bradykinin dilates efferent arterioles via release of efferent arteriole epoxyeicosatrienoic acids when perfused retrograde (no glomerular autacoids). However, when efferent arterioles are perfused orthograde through the glomerulus, bradykinin-induced dilatation is caused by a balance between: (1) the glomerular vasoconstrictor 20-hydroxyeicosatetraenoic acid and vasodilator prostaglandins, and (2) epoxyeicosatrienoic acids from the efferent arteriole and possibly the glomerulus. However, the role of 20-hydroxyeicosatetraenoic acid has only been studied with a cyclooxygenase inhibitor, which may artificially enhance its production by shunting arachidonic acid into the cytochrome P450 pathway. We hypothesized that in the absence of cyclooxygenase inhibition, bradykinin induces release of 20-hydroxyeicosatetraenoic acid from the glomerulus, which blunts the vasodilator effect of bradykinin; and that prostaglandins released from glomeruli in response to bradykinin are generated by cyclooxygenase-1. Rabbit efferent arterioles preconstricted with norepinephrine were perfused orthograde from the end of the afferent arteriole.Bradykinin was added to the perfusate with or without a 20-hydroxyeicosatetraenoic acid antagonist (20-HEDE), epoxyeicosatrienoic acid synthesis inhibitor (MS-PPOH), and/or cyclooxygenase-1 (SC-58560) or cyclooxygenase-2 inhibitor (NS-398). Bradykinin-dependent dilatation was enhanced by 20-HEDE but blunted by MS-PPOH. When the inhibitors were present, bradykinin-induced dilatation was abolished by blockade of cyclooxygenase-1 but not cyclooxygenase-2. We concluded that: (1) in the absence of cyclooxygenase inhibitors, bradykinin causes the release of a glomerular vasoconstrictor (20-hydroxyeicosatetraenoic acid) that antagonizes the vasodilator effect of epoxyeicosatrienoic acids released from the efferent arteriole and perhaps from the glomerulus, and (2) bradykinin-induced vasodilatation is caused by the release of epoxyeicosatrienoic acids from the efferent arteriole and glomerular metabolites of cyclooxygenase-1. Key Words: glomerulus Ⅲ cyclooxygenase-1 Ⅲ 20-hydroxyeicosatetraenoic acid Ⅲ epoxyeicosatrienoic acid Ⅲ renal vascular resistance R enal kinins are released at both the luminal and basolateral sides of the nephron by kallikrein, which is located mainly in the connecting tubule. Kinins released from this segment could stimulate the release of vasoactive autacoids from the glomerulus, which in turn could regulate the resistance of the downstream efferent arteriole (Ef-Art). 1 Intrarenal bradykinin (BK) infusion decreases renal vascular resistance, thereby increasing renal blood flow. 2 BK B 2 receptors are located in both the glomerulus and the Ef-Art and are involved in the vasodilator effect of BK on the Ef-Art via epoxyeicosatrienoic acids (EETs). 1,3,4 In the glomerulus, activation of the B 2 receptor by BK is known to stimulate the phospholipase A 2 pathway, generating arachidonic acid. Glomerular cyclooxygenase (COX) metabolizes arachidonic acid to prostaglandin (PG) H 2...

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Regulation of cyclooxygenase expression in the kidney by dietary salt intake

Cited by 224 publications

References 31 publications

Bradykinin Regulates Cyclooxygenase-2 in Rat Renal Thick Ascending Limb Cells

Bradykinin Regulates Cyclooxygenase-2 in Rat Renal Thick Ascending Limb Cells

Low Tonicity Mediates a Downregulation of Cyclooxygenase-1 Expression by Furosemide in the Rat Renal Papilla

Glomerular Cytochrome P-450 and Cyclooxygenase Metabolites Regulate Efferent Arteriole Resistance

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