The Bradykinin B2 receptor is required for full expression of renal COX-2 and renin

Imig, John D.; Zhao, Xueying; Orengo, Sheyla R.; Dipp, Susana; El‐Dahr, Samir S.

doi:10.1016/j.peptides.2003.07.003

Cited by 18 publications

(19 citation statements)

References 33 publications

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“…In parallel, we further analyzed B 2 receptor-deficient mice and controls under steady-state conditions but failed to detect any changes with respect to COX-1 and -2, PGES, EP1 or EP3 protein abundance between strains either (results not shown); the localization of these products in mouse in our hands was not principally different from that in rat kidney. The absence of cortical COX-1 changes in the knockouts agrees with previous data from whole kidney extracts (21), so that the evidence is against specific interactions between the KKS and COX-1 or its metabolites in the late distal and collecting duct epithelia in early RVH. In fact, most of the available data have ascribed to the B 2 receptor function in early RVH an antihypertensive, protective role preferentially acting on the vascular side, buffering ANG II vasoconstrictor effects (7,25).…”

Section: Discussionsupporting

confidence: 89%

“…RVH was earlier shown to present with increased B 2 receptor density in both kidneys (11), which may be explanatory to the fact that abrogation of kinin function has been worsening the development of RVH, possibly via reduced prostaglandin formation and consequent reduction in renal blood flow and sodium excretory ability (25). The full expression of COX-2 further appears to require intact B 2 receptor function (21). Alternatively, however, Hoe-induced reduction of NOS1 expression in RVH may have interfered with COX-2 (7), possibly through a p38 MAPK-dependent pathway as recently proposed (10).…”

Section: Discussionmentioning

confidence: 99%

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Renal cortical regulation of COX-1 and functionally related products in early renovascular hypertension (rat)

Theilig¹,

Dębiec²,

Nafz³

et al. 2006

American Journal of Physiology-Renal Physiology

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volume regulation is modulated by the action of cyclooxygenases (COX) and the resulting generation of prostanoids. Epithelial expression of COX isoforms in the cortex directs COX-1 to the distal convolutions and cortical collecting duct, and COX-2 to the thick ascending limb. Partly colocalized are prostaglandin E synthase (PGES), the downstream enzyme for renal prostaglandin E 2 (PGE2) generation, and the EP receptors type 1 and 3. COX-1 and related components were studied in two kidney-one clip (2K1C) Goldblatt hypertensive rats with combined chronic ANG II or bradykinin B 2 receptor blockade using candesartan (cand) or the B 2 antagonist Hoechst 140 (Hoe). Rats (untreated sham, 2K1C, sham ϩ cand, 2K1C ϩ cand, sham ϩ Hoe, 2K1C ϩ Hoe) were treated to map expression of parameters controlling PGE 2 synthesis. In 2K1C, cortical COX isoforms did not change uniformly. COX-2 changed in parallel with NO synthase 1 (NOS1) expression with a raise in the clipped, but a decrease in the nonclipped side. By contrast, COX-1 and PGES were uniformly downregulated in both kidneys, along with reduced urinary PGE 2 levels, and showed no clear relations with the NO status. ANG II receptor blockade confirmed negative regulation of COX-2 by ANG II but blunted the decrease in COX-1 selectively in nonclipped kidneys. B 2 receptor blockade reduced COX-2 induction in 2K1C but had no clear effect on COX-1. We suggest that in 2K1C, COX-1 and PGES expression may fail to oppose the effects of renovascular hypertension through reduced prostaglandin signaling in late distal tubule and cortical collecting duct.cyclooxygenase; nitric oxide synthase; bradykinin RENOVASCULAR HYPERTENSION (RVH) is a form of secondary hypertension. The two kidney-one clip rodent model of RVH (2K1C; Goldblatt model) is similar to unilateral RVH in humans. The defect is highly dependent on the enhanced activity of the renin-angiotensin system (RAS). Decreased renal perfusion pressure in the compromised kidney maximally activates the RAS, and its inability to balance the rise in blood pressure is partly the result of elevated ANG II levels. The nonstenotic kidney is subject to elevated perfusion pressure, responding with "pressure natriuresis" to lower blood pressure by the excretion of sodium. In the light of systemically elevated ANG II levels and the distinct constellation of the renal perfusion pressures, the RVH model is considered by some to be wholly one of increased peripheral vascular resistance, whereas others emphasize the role of volume retention (13; for a review, see Ref. 14). For the latter, elevated ANG II levels prevail in both kidneys in short-term and maintenance phase affecting both tubular transport and renal hemodynamics thereby causing long-term impairments in sodium balance regulation (29,30).Biological mechanisms with protective effects against hypertension and organ damage have received continuous interest and have therefore been studied also in RVH. In particular, paracrine and endocrine systems with protective potency have been analyzed for...

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Renal cortical regulation of COX-1 and functionally related products in early renovascular hypertension (rat)

Theilig¹,

Dębiec²,

Nafz³

et al. 2006

American Journal of Physiology-Renal Physiology

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“…These knockout mice have been extensively studied in several laboratories and exhibit a number of physiological alterations relevant for cardiovascular function: enhanced effects of endogenous and exogenous argininevasopressin (Alfie et al, 1999) and exogenous angiotensin II (Cervenka et al, 2001), distorted renal development in the fetus with abnormal distal nephrons , reduced glomerular capillary surface area (Schanstra et al, 2003), decreased renin and cyclooxygenase (COX)-2 expression in the kidney (Imig et al, 2003), a state of insulin resistance (Duka et al, 2001b), and increased renal fibrosis in response to unilateral ureteral obstruction . Mild degenerative and fibrotic changes are observed in the myocardium of aging B 2 receptor knockout mice (Maestri et al, 2003).…”

Section: Classification Of the Kinin Receptor Familymentioning

confidence: 99%

International Union of Pharmacology. XLV. Classification of the Kinin Receptor Family: from Molecular Mechanisms to Pathophysiological Consequences

Marceau²,

et al. 2005

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“…It has been reported that both bradykinin and NO derived from nNOS regulate renal cortical COX-2 expression under certain conditions (6,14,15). To investigate whether bradykinin or NO derived from nNOS is involved in angiotensin II-induced stimulation of renal cortical COX-2 expression in the presence of ARBs, rats treated with the ARB candesartan and angiotensin II were administered the nNOS inhibitor 7-NI or the bradykinin B2 receptor antagonist HOE-140.…”

Section: Neither Bradykinin Nor Neuronal No Synthase (Nnos) Was Involmentioning

confidence: 99%

Renal cortical cyclooxygenase 2 expression is differentially regulated by angiotensin II AT ₁ and AT ₂ receptors

Zhang

Yao

Cheng

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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Macula densa cyclooxygenase 2 (COX-2)-derived prostaglandins serve as important modulators of the renin-angiotensin system, and cross-talk exists between these two systems. Cortical COX-2 induction by angiotensin-converting enzyme (ACE) inhibitors or AT 1 receptor blockers (ARBs) suggests that angiotensin II may inhibit cortical COX-2 by stimulating the AT1 receptor pathway. In the present studies we determined that chronic infusion of either hypertensive or nonhypertensive concentrations of angiotensin II attenuated cortical COX-2. Angiotensin II infusion reversed cortical COX-2 elevation induced by ACE inhibitors. However, we found that angiotensin II infusion further stimulated cortical COX-2 elevation induced by ARBs, suggesting a potential role for an AT 2 receptor-mediated pathway when the AT1 receptor was inhibited. Both WT and AT2 receptor knockout mice were treated for 7 days with either ACE inhibitors or ARBs. Cortical COX-2 increased to similar levels in response to ACE inhibition in both knockout and WT mice. In WT mice ARBs increased cortical COX-2 more than ACE inhibitors, and this stimulation was attenuated by the AT2 receptor antagonist PD123319. In the knockout mice ARBs led to significantly less cortical COX-2 elevation, which was not attenuated by PD123319. PCR confirmed AT1a and AT2 receptor expression in the cultured macula densa cell line MMDD1. Angiotensin II inhibited MMDD1 COX-2, and CGP42112A, an AT2 receptor agonist, stimulated MMDD1 COX-2. In summary, these results demonstrate that macula densa COX-2 expression is oppositely regulated by AT1 and AT2 receptors and suggest that AT2 receptor-mediated cortical COX-2 elevation may mediate physiologic effects that modulate AT1-mediated responses. macula densa ͉ prostaglandin ͉ ACE inhibitor ͉ ARB T he conversion of arachidonic acid to prostaglandin H 2 by prostaglandin G 2 ͞H 2 synthase [cyclooxygenase (COX)] is a key enzymatic step that regulates the biosynthesis of prostaglandins and thromboxane. Prostaglandins regulate vascular tone and salt and water homeostasis in the mammalian kidney. Although inhibition of COX activity does not profoundly affect mammalian renal function under steady-state conditions, in conditions associated with increased angiotensin II production COX inhibition may lead to significant alterations in renal hemodynamics and function (1).In the kidney constitutive COX-1 is localized to mesangial cells, arteriolar endothelial cells, parietal epithelial cells of Bowman's capsule, and cortical and medullary collecting ducts. In contrast, in normal adult mammalian kidney COX-2 expression is localized to the macula densa and associated cortical thick ascending limb of Henle (cTAL) in the cortex and to a subset of medullary interstitial cells near the papillary tip (2). After chronic salt depletion, COX-2 expression in macula densa͞cTAL increases significantly, and macula densa-derived COX-2 metabolites have been implicated as modulators of the renin-angiotensin-aldosterone system by increasing renin expression and secretio...

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The Bradykinin B2 receptor is required for full expression of renal COX-2 and renin

Cited by 18 publications

References 33 publications

Renal cortical regulation of COX-1 and functionally related products in early renovascular hypertension (rat)

Renal cortical regulation of COX-1 and functionally related products in early renovascular hypertension (rat)

International Union of Pharmacology. XLV. Classification of the Kinin Receptor Family: from Molecular Mechanisms to Pathophysiological Consequences

Renal cortical cyclooxygenase 2 expression is differentially regulated by angiotensin II AT ₁ and AT ₂ receptors

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The Bradykinin B2 receptor is required for full expression of renal COX-2 and renin

Cited by 18 publications

References 33 publications

Renal cortical regulation of COX-1 and functionally related products in early renovascular hypertension (rat)

Renal cortical regulation of COX-1 and functionally related products in early renovascular hypertension (rat)

International Union of Pharmacology. XLV. Classification of the Kinin Receptor Family: from Molecular Mechanisms to Pathophysiological Consequences

Renal cortical cyclooxygenase 2 expression is differentially regulated by angiotensin II AT 1 and AT 2 receptors

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Renal cortical cyclooxygenase 2 expression is differentially regulated by angiotensin II AT ₁ and AT ₂ receptors