(Hypertension. 1997;29:315.)
© 1997 American Heart Association, Inc.
Arthur C. Corcoran Memorial Lecture |
Inhibition of Renal Outer Medullary 20-HETE Production Produces Hypertension in Lewis Rats
From the Department of Physiology, Medical College of Wisconsin (Milwaukee).
Reprint requests to Richard J. Roman, Department of Physiology, Medical College of Wisconsin, 8701 Watertown Plank Rd, Milwaukee, WI 53226
Recent studies have indicated that a deficiency in the production of 20-hydroxyeicosatetraenoic acid (20-HETE) in the outer medulla of the kidney may contribute to the abnormalities in the renal handling of sodium and the development of hypertension in Dahl salt-sensitive rats. To determine whether a reduction in 20-HETE production in the outer medulla is sufficient to induce hypertension, an inhibitor of the renal metabolism of arachidonic acid by P450 enzymes, 17-octadecenoic acid (17-ODYA), was chronically infused directly into the outer medulla of the left kidney of uninephrectomized Lewis rats fed a high salt diet. Renal medullary interstitial infusion of 17-ODYA (400 pmol/min) reduced the formation of 20-HETE in the outer medulla of the infused kidney by 70% compared with values seen in the right kidney collected when the rat was uninephrectomized, but it had no effect on the production of 20-HETE in the renal cortex. After 5 days, mean arterial pressure rose from 115±2 to 142±2 mm Hg (n=6) in the rats infused with 17-ODYA, while mean arterial pressure was not significantly altered in the rats infused with vehicle alone (116±1 versus 117±2 mm Hg, n=6). These results suggest that inhibition of the renal metabolism of arachidonic acid by P450 enzymes in the outer medulla of the kidney is sufficient to induce the development of hypertension in Lewis rats fed a high salt diet and support the view that P450 metabolites of arachidonic acid play an important role in the regulation of renal function and the long-term control of arterial pressure.
Key Words: cytochrome P450 • kidney • eicosanoids • P450 inhibitors
Abbreviations: AA = arachidonic acid • HETE = hydroxyeicosatetraenoic acid • 17-ODYA = 17-octadecenoic acid • OM = outer medulla, outer medullary • SS = salt-sensitive • TAL = thick ascending limb of Henle’s loop
This article has been cited by other articles:
 |
|
 |
|
  J. M. Williams, A. Sarkis, K. M. Hoagland, K. Fredrich, R. P. Ryan, C. Moreno, B. Lopez, J. Lazar, F. J. Fenoy, M. Sharma, et al. Transfer of the CYP4A region of chromosome 5 from Lewis to Dahl S rats attenuates renal injury Am J Physiol Renal Physiol, December 1, 2008; 295(6): F1764 - F1777. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Vera, S. Kelsen, and D. E. Stec Kidney-Specific Induction of Heme Oxygenase-1 Prevents Angiotensin II Hypertension Hypertension, October 1, 2008; 52(4): 660 - 665. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. L. Laffer, J. V. Gainer, M. R. Waterman, J. H. Capdevila, M. Laniado-Schwartzman, A. Nasjletti, N. J. Brown, and F. Elijovich The T8590C Polymorphism of CYP4A11 and 20-Hydroxyeicosatetraenoic Acid in Essential Hypertension Hypertension, March 1, 2008; 51(3): 767 - 772. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. E. Stec, R. J. Roman, A. Flasch, and M. J. Rieder Functional polymorphism in human CYP4F2 decreases 20-HETE production Physiol Genomics, June 19, 2007; 30(1): 74 - 81. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Yu, B. Lopez, E. A. Dos Santos, J. R. Falck, and R. J. Roman Effects of 20-HETE on Na+ transport and Na+-K+-ATPase activity in the thick ascending loop of Henle Am J Physiol Regulatory Integrative Comp Physiol, June 1, 2007; 292(6): R2400 - R2405. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Williams, A. Sarkis, B. Lopez, R. P. Ryan, A. K. Flasch, and R. J. Roman Elevations in Renal Interstitial Hydrostatic Pressure and 20-Hydroxyeicosatetraenoic Acid Contribute to Pressure Natriuresis Hypertension, March 1, 2007; 49(3): 687 - 694. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. J. Roman, K. M. Hoagland, B. Lopez, A. E. Kwitek, M. R. Garrett, J. P. Rapp, J. Lazar, H. J. Jacob, and A. Sarkis Characterization of blood pressure and renal function in chromosome 5 congenic strains of Dahl S rats Am J Physiol Renal Physiol, June 1, 2006; 290(6): F1463 - F1471. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Williams, X. Zhao, M. H. Wang, J. D. Imig, and D. M. Pollock Peroxisome Proliferator-Activated Receptor-{alpha} Activation Reduces Salt-Dependent Hypertension During Chronic Endothelin B Receptor Blockade Hypertension, August 1, 2005; 46(2): 366 - 371. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. A. Dos Santos, A. J. Dahly-Vernon, K. M. Hoagland, and R. J. Roman Inhibition of the formation of EETs and 20-HETE with 1-aminobenzotriazole attenuates pressure natriuresis Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2004; 287(1): R58 - R68. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. L. Laffer, M. Laniado-Schwartzman, A. Nasjletti, and F. Elijovich 20-HETE and Circulating Insulin in Essential Hypertension With Obesity Hypertension, February 1, 2004; 43(2): 388 - 392. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. M. Hoagland, A. K. Flasch, and R. J. Roman Inhibitors of 20-HETE Formation Promote Salt-Sensitive Hypertension in Rats Hypertension, October 1, 2003; 42(4): 669 - 673. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. L. Laffer, M. Laniado-Schwartzman, M.-H. Wang, A. Nasjletti, and F. Elijovich Differential Regulation of Natriuresis by 20-Hydroxyeicosatetraenoic Acid in Human Salt-Sensitive Versus Salt-Resistant Hypertension Circulation, February 4, 2003; 107(4): 574 - 578. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Xu, W. O. Straub, W. Pak, P. Su, K. G. Maier, M. Yu, R. J. Roman, P. R. Ortiz De Montellano, and D. L. Kroetz Antihypertensive effect of mechanism-based inhibition of renal arachidonic acid omega -hydroxylase activity Am J Physiol Regulatory Integrative Comp Physiol, September 1, 2002; 283(3): R710 - R720. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M.-H. Wang, B. A. Zand, A. Nasjletti, and M. Laniado-Schwartzman Renal 20-hydroxyeicosatetraenoic acid synthesis during pregnancy Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2002; 282(2): R383 - R389. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. T. Botros, M. Laniado-Schwartzman, and N. G. Abraham Regulation of Cyclooxygenase- and Cytochrome P450-Derived Eicosanoids by Heme Oxygenase in the Rat Kidney Hypertension, February 1, 2002; 39(2): 639 - 644. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. J. Roman P-450 Metabolites of Arachidonic Acid in the Control of Cardiovascular Function Physiol Rev, January 1, 2002; 82(1): 131 - 185. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Lopez, C. Moreno, M. G. Salom, R. J. Roman, and F. J. Fenoy Role of guanylyl cyclase and cytochrome P-450 on renal response to nitric oxide Am J Physiol Renal Physiol, September 1, 2001; 281(3): F420 - F427. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Quigley, M. Baum, K. M. Reddy, J. C. Griener, and J. R. Falck Effects of 20-HETE and 19(S)-HETE on rabbit proximal straight tubule volume transport Am J Physiol Renal Physiol, June 1, 2000; 278(6): F949 - F953. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. Lasker, W. B. Chen, I. Wolf, B. P. Bloswick, P. D. Wilson, and P. K. Powell Formation of 20-Hydroxyeicosatetraenoic Acid, a Vasoactive and Natriuretic Eicosanoid, in Human Kidney. ROLE OF CYP4F2 AND CYP4A11 J. Biol. Chem., February 11, 2000; 275(6): 4118 - 4126. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. H. Capdevila, J. R. Falck, and R. C. Harris Cytochrome P450 and arachidonic acid bioactivation: molecular and functional properties of the arachidonate monooxygenase J. Lipid Res., February 1, 2000; 41(2): 163 - 181. [Abstract] [Full Text]
|
|
|
|
|
|
O. Ito and R. J. Roman Regulation of P-450 4A activity in the glomerulus of the rat Am J Physiol Regulatory Integrative Comp Physiol, June 1, 1999; 276(6): R1749 - R1757. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. P. E. Van Dokkum, M. Alonso-Galicia, A. P. Provoost, H. J. Jacob, and R. J. Roman Impaired autoregulation of renal blood flow in the fawn-hooded rat Am J Physiol Regulatory Integrative Comp Physiol, January 1, 1999; 276(1): R189 - R196. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Ito and R. J. Roman Role of 20-HETE in Elevating Chloride Transport in the Thick Ascending Limb of Dahl SS/Jr Rats Hypertension, January 1, 1999; 33(1): 419 - 423. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Su, K. M. Kaushal, and D. L. Kroetz Inhibition of renal arachidonic acid omega -hydroxylase activity with ABT reduces blood pressure in the SHR Am J Physiol Regulatory Integrative Comp Physiol, August 1, 1998; 275(2): R426 - R438. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. K. Powell, I. Wolf, R. Jin, and J. M. Lasker Metabolism of Arachidonic Acid to 20-Hydroxy-5,8,11,14-eicosatetraenoic Acid by P450 Enzymes in Human Liver: Involvement of CYP4F2 and CYP4A11 J. Pharmacol. Exp. Ther., June 1, 1998; 285(3): 1327 - 1336. [Abstract] [Full Text]
|
|
|
|
|
|
O. Ito, M. Alonso-Galicia, K. A. Hopp, and R. J. Roman Localization of cytochrome P-450 4A isoforms along the rat nephron Am J Physiol Renal Physiol, February 1, 1998; 274(2): F395 - F404. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. W. Wilson, M. Alonso-Galicia, and R. J. Roman Effects of Lipid-Lowering Agents in the Dahl Salt-Sensitive Rat Hypertension, January 1, 1998; 31(1): 225 - 231. [Abstract] [Full Text] [PDF]
|
|