Epoxyeicosatrienoic acids mediate adenosine‐induced vasodilation in rat preglomerular microvessels (PGMV) <i>via</i> A<sub>2A</sub> receptors

Cheng, Monica K.; Doumad, Anabel B.; Jiang, Houli; Falck, John R.; McGiff, John C.; Carroll, Mairéad A.

doi:10.1038/sj.bjp.0705640

Cited by 56 publications

(73 citation statements)

References 46 publications

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“…18,47 EETs have been reported to exhibit diverse biologic activities, including dilation of preglomerular microvessels, 48 stimulation of angiogenesis, 49 and inhibition of sodium transport. 20 It is reported that 8,9-and 14,15-EET could also regulate BK channels 23,24 ; however, the observation that only 11,12-EET stimulates BK channels strongly suggests that 11,12-EET mediates the effect of AA on BK channels in the CCD.…”

Section: Discussionmentioning

confidence: 99%

Epoxyeicosatrienoic Acid Activates BK Channels in the Cortical Collecting Duct

Sun

Lin

et al. 2009

Journal of the American Society of Nephrology

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The cortical collecting duct (CCD), which is involved in renal potassium (K) excretion, expresses cytochrome P450 (CYP)-epoxygenase. Here, we examined the effect of high dietary K on renal expression of CYP2C23 and CYP2J2 in the rat, as well as the role of CYP-epoxygenase-dependent metabolism of arachidonic acid in the regulation of Ca 2ϩ -activated big-conductance K (BK) channels. By Western blot analysis, high dietary K stimulated the expression of CYP2C23 but not CYP2J2 and increased 11,12-epoxyeicosatrienoic acid (11,12-EET) levels in isolated rat CCD tubules. Application of arachidonic acid increased BK channel activity, and this occurred to a greater extent in rats on a high-K diet compared with a normal-K diet. This effect was unlikely due to arachidonic acid-induced changes in membrane fluidity, because 11,14,17-eicosatrienoic acid did not alter BK channel activity. Inhibiting CYP-epoxygenase but not cyclooxygenase-or CYP--hydroxylase-dependent pathways completely abolished the stimulatory effect of arachidonic acid on BK channel activity. In addition, application of 11,12-EET mimicked the effect of arachidonic acid on BK channel activity, even in the presence of CYP-epoxygenase inhibition. This effect seemed specific to 11,12-EET, because both 8,9-and 14,15-EET failed to stimulate BK channels. Finally, inhibition of CYP-epoxygenase abolished iberiotoxin-sensitive and flow-stimulated but not basal net K secretion in isolated microperfused CCD. In conclusion, high dietary K stimulates the renal CYP-epoxygenase pathway, which plays an important role in activating BK channels and flowstimulated K secretion in the CCD.

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Section: Discussionmentioning

confidence: 99%

Epoxyeicosatrienoic Acid Activates BK Channels in the Cortical Collecting Duct

Sun

Lin

et al. 2009

Journal of the American Society of Nephrology

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“…Stimulation of A 1 receptor has been shown to cause inhibition of adenylate cyclase, decrease in cAMP concentrations, activation of PKC, and stimulation of phospholapase A 2 (PLA2) (26), whereas stimulation of A 2a or A 2b receptor has been reported to increase cAMP production and stimulate PKA (26). Recently, it has also been reported that stimulation of A 2a receptor increases 11,12-and 5,6-EET in the kidney (6). The RT-PCR analysis has detected A 1 and A 2b adenosine receptor mRNAs, whereas the band intensity for A 2a adenosine receptor mRNA is low in the TAL (28,33).…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, it has been shown that EET activates Gs protein and Src family PTK (25). For instance, 11,12-EET has been reported to enhance PKA activity by increasing cAMP formation in the smooth muscle of renal vessels (6). Also, 14,15-EET has been demonstrated to activate PTK-dependent signaling (5).…”

Section: Discussionmentioning

confidence: 99%

Dietary K intake regulates the response of apical K channels to adenosine in the thick ascending limb

Wei

Wang

2004

American Journal of Physiology-Renal Physiology

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We used the patch-clamp technique to study the effect of adenosine on the apical 70-pS K channel in the thick ascending limb (TAL) of the rat kidney. Application of 1 M cyclohexyladenosine (CHA), an adenosine analog, stimulated apical 70-pS K channel activity and increased the product of channel open probability and channel number (NP o) from 0.34 to 0.7. Also, addition of CGS-21680, a specific A 2a adenosine receptor agonist, mimicked the effect of CHA and increased NP o from 0.33 to 0.77. The stimulatory effect of CHA and CGS-21680 was completely blocked by H89, an inhibitor of protein kinase A (PKA), or by inhibition of adenylate cyclase with SQ-22536. This suggests that the stimulatory effect of adenosine analogs is mediated by a PKA-dependent pathway. The effect of adenosine analog was almost absent in the TAL from rats on a K-deficient (KD) diet for 7 days. Application of DDMS, an agent that inhibits cytochrome P-450 hydrolase, not only significantly increased the activity of the 70-pS K channel but also restored the stimulatory effect of CHA on the 70-pS K channel in the TAL from rats on a KD diet. Also, the effect of CHA was absent in the presence of 20-HETE. Inhibition of PKA blocked the stimulatory effect of CHA on the apical 70-pS K channel in the presence of DDMS in the TAL from rats on a KD diet. We conclude that stimulation of adenosine receptor increases the apical 70-pS K channel activity via a PKA-dependent pathway and that the effect of adenosine on the apical 70-pS K channel is suppressed by low-K intake. Moreover, the diminished response to adenosine is the result of increase in 20-HETE formation, which inhibits the cAMP-dependent pathway in the TAL from rats on a KD diet. adenosine receptor; adenosine 3Ј,5Ј-cyclic monophosphate; protein kinase A; cytochrome P-450 hydroxylase; arachidonic acid; 20-hydroxyeicosatetraenoic acid ADENOSINE IS GENERATED FROM the hydrolysis of ATP via

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“…A 2 receptor-mediated vasodilation results from stimulation of G s , leading to increased cAMP that is partially mediated via epoxyeicosatrienoic acid (EETs) release (7). Cytochrome P-450 epoxygenase metabolites alter vascular tone in afferent arterioles and modify the autoregulatory efficiency of the preglomerular microcirculation (8,20). Activation of A 2 receptor stimulates EETs in preglomerular microvessels, suggesting that it may affect the following major indexes of renal function: renal vascular resistance, glomerular filtration rate, renal interstitial pressure, and medullary blood flow (8).…”

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confidence: 99%

“…Cytochrome P-450 epoxygenase metabolites alter vascular tone in afferent arterioles and modify the autoregulatory efficiency of the preglomerular microcirculation (8,20). Activation of A 2 receptor stimulates EETs in preglomerular microvessels, suggesting that it may affect the following major indexes of renal function: renal vascular resistance, glomerular filtration rate, renal interstitial pressure, and medullary blood flow (8). Adenosine also dilates efferent arterioles at concentrations compatible with activation of the A 2B receptor subtype (1).…”

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confidence: 99%

Afferent arteriolar vasodilator effect of adenosine predominantly involves adenosine A_2B receptor activation

Feng

Navar

2010

American Journal of Physiology-Renal Physiology

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Feng MG, Navar LG. Afferent arteriolar vasodilator effect of adenosine predominantly involves adenosine A2B receptor activation. Am J Physiol Renal Physiol 299: F310 -F315, 2010. First published May 12, 2010 doi:10.1152/ajprenal.00149.2010.-Adenosine is an important paracrine agent regulating renal vascular tone via adenosine A1 and A2 receptors. While A2B receptor message and protein have been localized to preglomerular vessels, functional evidence on the role of A2B receptors in mediating the vasodilator action of adenosine on afferent arterioles is not available. The present study determined the role of A2B receptors in mediating the afferent arteriolar dilation and compared the effects of A2B and A2A receptor blockade on afferent arterioles. We used the rat in vitro blood-perfused juxtamedullary nephron technique combined with videomicroscopy. Single afferent arterioles of Sprague-Dawley rats were visualized and superfused with solutions containing adenosine or adenosine A2 receptor agonist (CV-1808) along with adenosine A2B and A2A receptor blockers. Adenosine (10 mol/l) caused modest constriction and subsequent superfusion with SCH-58261 (SCH), an A2A receptor blocker, at concentrations up 10 mol/l elicited only slight additional decreases in afferent arteriolar diameter with maximum effect at a concentration of 1 mol/l (Ϫ11.0 Ϯ 2.5%, n ϭ 6, P Ͻ 0.05). However, superfusion of adenosine-treated vessels with MRS-1754 (MRS), an A2B receptor blocker, elicited greater decreases in afferent arteriolar diameter (Ϫ26.0 Ϯ 4.7%, n ϭ 5, P Ͻ 0.01). SCH did not significantly augment the adenosine-mediated afferent constriction elicited by MRS; however, adding MRS after SCH caused further significant vasoconstriction. Superfusion with CV-1808 dilated afferent arterioles (17.2 Ϯ 2.4%, n ϭ 6, P Ͻ 0.01). This effect was markedly attenuated by MRS (Ϫ22.6 Ϯ 2.0%, n ϭ 5, P Ͻ 0.01) but only slightly reduced by SCH (Ϫ9.0 Ϯ 1.1%, n ϭ 5, P Ͻ 0.05) and completely prevented by adding MRS after SCH (Ϫ24.7 Ϯ 1.8%, n ϭ 5, P Ͻ 0.01). These results indicate that, while both A2A and A2B receptors are functionally expressed in juxtamedullary afferent arterioles, the powerful vasodilating action of adenosine predominantly involves A2B receptor activation, which counteracts A1 receptor-mediated vasoconstriction. adenosine receptor antagonists; renal microcirculation; vascular biology; afferent arterioles; kidney ADENOSINE IS AN ENDOGENOUS purine nucleoside derived from the degradation of ATP/AMP and serves as a paracrine agent influencing many physiological processes. Four subtypes of adenosine receptors have been identified: A 1 , A 2A , A 2B , and A 3 ; all are guanine nucleotide-binding protein (G)-coupled receptors (6,15,25,26,28,29), which are characterized by their capacity to either increase or decrease intracellular cAMP levels (13). A 2A and A 2B receptors are coupled to G s protein signaling and mediate biological effects opposite to A 1 and A 3 receptors, which are coupled to G i protein signaling (13). All four subtypes of aden...

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Epoxyeicosatrienoic acids mediate adenosine‐induced vasodilation in rat preglomerular microvessels (PGMV) via A_2A receptors

Cited by 56 publications

References 46 publications

Epoxyeicosatrienoic Acid Activates BK Channels in the Cortical Collecting Duct

Epoxyeicosatrienoic Acid Activates BK Channels in the Cortical Collecting Duct

Dietary K intake regulates the response of apical K channels to adenosine in the thick ascending limb

Afferent arteriolar vasodilator effect of adenosine predominantly involves adenosine A_2B receptor activation

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Epoxyeicosatrienoic acids mediate adenosine‐induced vasodilation in rat preglomerular microvessels (PGMV) via A2A receptors

Cited by 56 publications

References 46 publications

Epoxyeicosatrienoic Acid Activates BK Channels in the Cortical Collecting Duct

Epoxyeicosatrienoic Acid Activates BK Channels in the Cortical Collecting Duct

Dietary K intake regulates the response of apical K channels to adenosine in the thick ascending limb

Afferent arteriolar vasodilator effect of adenosine predominantly involves adenosine A2B receptor activation

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Epoxyeicosatrienoic acids mediate adenosine‐induced vasodilation in rat preglomerular microvessels (PGMV) via A_2A receptors

Afferent arteriolar vasodilator effect of adenosine predominantly involves adenosine A_2B receptor activation