HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 285/5/F955    most recent 00092.2003v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (5) Citing Articles via Google Scholar Google Scholar Articles by Ogungbade, G. O. Articles by Oyekan, A. O. Search for Related Content PubMed PubMed Citation Articles by Ogungbade, G. O. Articles by Oyekan, A. O.

Role of epoxyeicosatrienoic acids in renal functional response to inhibition of NO production in the rat

¹Center for Cardiovascular Diseases, College of Pharmacy and Health Sciences, Texas Southern University, Houston, Texas 77004; and ²Department of Pharmacology, New York Medical College, Valhalla, New York 10595

Submitted 28 February 2003 ; accepted in final form 20 June 2003

Nitric oxide (NO) inhibits hemoproteins, including cytochrome (CYP) 2C, the gene responsible for the production of epoxyeicosatrienoic acids (EETs). EETs and NO are produced in the kidney, and both regulate renal vascular tone and Na⁺ transport. However, the role of EETs in NO-mediated renal function is not known. This study tested the hypothesis that NO tonically regulates the renal production of EETs, thereby impacting renal vasomotor tone and electrolyte balance. LPS (10 mg/kg iv) inhibited microsomal conversion of ¹⁴C-labeled arachidonic acid to EETs and reduced mean arterial blood pressure (MABP; = 63 ± 5 mmHg). Nitro-L-arginine methyl ester (L-NAME, 10 mg/kg), an inhibitor of NO synthase, increased MABP ( = 26 ± 6 mmHg), reduced cortical (CBF) and medullary (MBF) blood flow ( = -0.86 ± 0.15 and -0.34 ± 0.09 V, respectively) and glomerular filtration rate (GFR; from 0.82 ± 0.16 to 0.32 ± 0.10 ml·g kidney^-1·min^-1), and increased Na⁺ excretion (U_NaV, from 0.16 ± 0.04 to 0.30 ± 0.06 µmol·g kidney^-1·min^-1). 2-(2-Propynyloxy)-benzenehexanoic acid (PPOH), a suicide substrate inhibitor of EET production, did not affect the L-NAME-induced increase in MABP but attenuated the effects of L-NAME on CBF (31 ± 7%, P < 0.05%), GFR (44 ± 6%, P < 0.05), and U_NaV (78 ± 7%, P < 0.05). Miconazole (1.3 mg·kg^-1·h^-1), a heme inhibitor of epoxygenase enzymes, produced effects similar to those of PPOH. Renal intraarterial infusion of 5,6-, 8,9-, 11,12-, and 14,15-EET (1-10 ng/min) elicited dose-dependent reductions in CBF and GFR accompanied by regioisomeric changes in MBF, U_NaV, and urine flow rate. In addition, 11,12-EET dose dependently restored the PPOH blunting the effects of L-NAME on CBF, MBF, and GFR. We conclude that NO tonically regulates epoxygenase activity and that EETs are renal vaosoconstrictors in vivo and contribute, at least in part, to the renal functional responses following inhibition of NO production.

cytochrome P-450; kidney

This article has been cited by other articles:

				H. Huang, C. Morisseau, J. Wang, T. Yang, J. R. Falck, B. D. Hammock, and M.-H. Wang Increasing or stabilizing renal epoxyeicosatrienoic acid production attenuates abnormal renal function and hypertension in obese rats Am J Physiol Renal Physiol, July 1, 2007; 293(1): F342 - F349. [Abstract] [Full Text] [PDF]

				N. W. Rajapakse, R. J. Roman, J. R. Falck, J. J. Oliver, and R. G. Evans Modulation of V1-receptor-mediated renal vasoconstriction by epoxyeicosatrienoic acids Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2004; 287(1): R181 - R187. [Abstract] [Full Text] [PDF]