This Article Full Text Full Text (PDF) All Versions of this Article: 45/1/103    most recent 01.HYP.0000150782.28485.91v1 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 PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Zhang, F. Articles by Nasjletti, A. Search for Related Content PubMed PubMed Citation Articles by Zhang, F. Articles by Nasjletti, A. Related Collections Other hypertension Other Vascular biology

(Hypertension. 2005;45:103.)
© 2005 American Heart Association, Inc.

Scientific Contributions

Decreased Levels of Cytochrome P450 2E1–Derived Eicosanoids Sensitize Renal Arteries to Constrictor Agonists in Spontaneously Hypertensive Rats

Fan Zhang; Huan Deng; Rowena Kemp; Harpreet Singh; Venkat Raj Gopal; John R. Falck; Michal Laniado-Schwartzman; Alberto Nasjletti

From the Department of Pharmacology (F.Z., H.D., R.K., H.S., M.L.-S., A.N.), New York Medical College, Valhalla, NY; and Departments of Biochemistry and Pharmacology (V.R.G., J.R.F.), University of Texas Southwestern Medical School, Dallas.

Correspondence to Alberto Nasjletti, MD, Department of Pharmacology, New York Medical College, Valhalla, NY 10595. E-mail alberto_nasjletti{at}nymc.edu

We compared renal interlobar arteries of spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) in terms of cytochrome P450 (CYP) 4A and CYP2E1 protein expression; levels of 20-HETE, 19-HETE, and 18-HETE; and responsiveness to phenylephrine in the absence and presence of N-methylsulfonyl-12,12-dibromododec-11-enamide (DDMS; 30 µmol/L), a CYP4A inhibitor. Relative to data in WKY, arteries of SHR exhibited diminished (P<0.05) CYP2E1 and levels of 19-HETE (66.7±6.0 versus 44.9±2.8 pmol/mg) and 18-HETE (13.8±1.6 versus 7.9±0.5 pmol/mg), whereas CYP4A and 20-HETE levels (99.3±9.1 versus 98.9±12.8 pmol/mg) were unchanged. Phenylephrine contracted vascular rings of SHR and WKY; the R_max was similar in both strains, but SHR vessels were more sensitive as denoted by the lower (P<0.05) EC₅₀ (0.28±0.07 versus 0.71±0.12 µmol/L). DDMS decreased 20-HETE and, to a lesser extent, 19-HETE, while increasing (P<0.05) the EC₅₀ for phenylephrine by 475% and 54% in vessels of SHR and WKY, respectively. The desensitizing effect of DDMS was reversed by 20-HETE. Notably, the minimal concentration of 20-HETE that decreased the EC₅₀ for phenylephrine in DDMS-treated vessels was smaller in SHR (0.1 µmol/L) than WKY (10 µmol/L), and the sensitizing effect of 20-HETE was blunted (P<0.05) by the (R) stereoisomers of 19-HETE and 18-HETE. We conclude that the increased sensitivity to phenylephrine in arteries of SHR is attributable to a vasoregulatory imbalance produced by a deficit in vascular CYP2E1-derived products, most likely 19(R)-HETE and 18(R)-HETE, which condition amplification of the sensitizing action of 20-HETE.

Key Words: rats, spontaneously hypertensive • vasoconstriction • kidney

This article has been cited by other articles:

				J. Cheng, J.-S. Ou, H. Singh, J. R. Falck, D. Narsimhaswamy, K. A. Pritchard Jr., and M. L. Schwartzman 20-Hydroxyeicosatetraenoic acid causes endothelial dysfunction via eNOS uncoupling Am J Physiol Heart Circ Physiol, February 1, 2008; 294(2): H1018 - H1026. [Abstract] [Full Text] [PDF]

				I. Fleming and R. Busse Endothelium-Derived Epoxyeicosatrienoic Acids and Vascular Function Hypertension, April 1, 2006; 47(4): 629 - 633. [Abstract] [Full Text] [PDF]