Background/Aims: Adenosine (ADO) causes vasodilation in most tissues. In the kidney it can induce vasoconstriction or vasodilation, depending on the prevailing stimulation of A1 or A2 receptors (A1R, A2R). ADO-induced alterations of renal excretion may be secondary to haemodynamic changes, or reflect a direct influence on tubular transport. This whole-kidney study explored renal excretory responses to ADO receptor stimulation as related to renal haemodynamics sodium intake and cytochrome P450 (CYP-450) activity. Methods: The effects of ADO or an A2aR agonist (DPMA) on urine flow (V), sodium excretion (UNaV) and total solute excretion were examined in anaesthetized Wistar rats on a low-sodium or high-sodium (HS) diet. Total renal blood flow (RBF; renal artery probe), and outer- and inner-medullary blood flows (OM-BF, IM-BF; laser-Doppler fluxes) were also determined. Results: Consistent opposed effects of ADO and DPMA were only observed with the HS diet. ADO increased V (150%) and UNaV (100%); there were also significant increases in RBF, OM-BF and IM-BF. These changes were prevented by 1-aminobenzotriazol, a CYP-450 inhibitor. In HS rats, DPMA significantly decreased arterial blood pressure and renal excretion. Conclusions: Post-ADO diuresis/natriuresis was in part secondary to renal hyperperfusion; the response was probably mediated by CYP-450-dependent active agents. Selective A2aR stimulation induced systemic vasodilation, major hypotension, and a secondary decrease in renal excretion.

1.
Hansen PB, Schnermann J: Vasoconstrictor and vasodilator effects of adenosine in the kidney. Am J Physiol Renal Physiol 2003;285:F590-F599.
2.
Vallon V, Muhlbauer B, Osswald H: Adenosine and kidney function. Physiol Rev 2006;86:901-940.
3.
Di Sole F: Adenosine and renal tubular function. Curr Opin Nephrol Hypertens 2008;17:399-407.
4.
Siragy HM, Linden J: Sodium intake markedly alters renal interstitial fluid adenosine. Hypertension 1996;27:404-407.
5.
Zou AP, Wu F, Li PL, Cowley AW Jr: Effect of chronic salt loading on adenosine metabolism and receptor expression in renal cortex and medulla in rats. Hypertension 1999;33:511-516.
6.
Liclican EL, McGiff JC, Pedraza PL, Ferreri NR, Falck JR, Carroll MA: Exaggerated response to adenosine in kidneys from high salt-fed rats: role of epoxyeicosatrienoic acids. Am J Physiol Renal Physiol 2005;289:F386-F392.
7.
Liclican EL, McGiff JC, Falck JR, Carroll MA: Failure to upregulate the adenosine 2A receptor-epoxyeicosatrienoic acid pathway contributes to the development of hypertension in Dahl salt-sensitive rats. Am J Physiol Renal Physiol 2008;295:F1696-F1704.
8.
Dobrowolski L, Kompanowska-Jezierska E, Walkowska A, Sadowski J: Sodium intake determines the role of adenosine A2 receptors in control of renal medullary perfusion in the rat. Nephrol Dial Transplant 2007;22:2805-2809.
9.
Kulick A, Panico C, Gill P, Welch WJ: Low salt intake increases adenosine type 1 receptor expression and function in the rat proximal tubule. Am J Physiol Renal Physiol 2008;295:F37-F41.
10.
Smith JA, Whitaker EM, Yaktubay N, Morton MJ, Bowmer CJ, Yates MS: Regulation of renal adenosine A1 receptors: effect of dietary sodium chloride. Eur J Pharmacol 1999;384:71-79.
11.
Carroll MA, Cheng MK, Liclican EL, Li J, Doumad AB, McGiff JC: Purinoceptors in renal microvessels: adenosine-activated and cytochrome P450 monooxygenase-derived arachidonate metabolites. Pharmacol Rep 2005;57:191-195.
12.
Carroll MA, Doumad AB, Li J, Cheng MK, Falck JR, McGiff JC: Adenosine2A receptor vasodilation of rat preglomerular microvessels is mediated by EETs that activate the cAMP/PKA pathway. Am J Physiol Renal Physiol 2006;291:F155-F161.
13.
Nayeem MA, Zeldin DC, Boegehold MA, Falck JR: Salt modulates vascular response through adenosine A2A receptor in eNOS-null mice: role of CYP450 epoxygenase and soluble epoxide hydrolase. Mol Cell Biochem 2011;350:101-111.
14.
Wang M, Sui H, Li W, Wang J, Liu Y, Gu L, Wang WH, Gu R: Stimulation of A2a adenosine receptor abolishes the inhibitory effect of arachidonic acid on the basolateral 50-pS K channel in the thick ascending limb. Am J Physiol Renal Physiol 2011;300:F906-F913.
15.
Wei Y, Sun P, Wang ZJ, Yang BF, Carroll MA, Wang WH: Adenosine inhibits ENaC via cytochrome P-450 epoxygenase-dependent metabolites of arachidonic acid. Am J Physiol Renal Physiol 2006;290:F1163-F1168.
16.
Dobrowolski L, Walkowska A, Kompanowska-Jezierska E, Kuczeriszka M, Sadowski J: Effects of ATP on rat haemodynamics and excretion: role of sodium intake, nitric oxide and cytochrome P450. Acta Physiol (Oxf) 2007;189:77-85.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.