(Hypertension. 1996;27:1329-1336.)
© 1996 American Heart Association, Inc.
Articles |
Renal Cytochrome P4504A Activity and Salt Sensitivity in Spontaneously Hypertensive Rats
From the Department of Physiology, Medical College of Wisconsin, Milwaukee (D.E.S., R.J.R.); Cardiovascular Research Center, Massachusetts General Hospital, Charlestown (M.R.T., H.J.J.); and São Paulo Heart Institute, University of São Paulo (Brazil) School of Medicine (J.E.K.).
Abstract Differences in the renal metabolism of arachidonic acid by cytochrome P450 have been reported in the spontaneously hypertensive rat (SHR) and Wistar-Koyto rats, but the contribution of this system to the development of hypertension is unclear. The present study compared renal P450 activity and blood pressure in SHR and Brown-Norway rats (BN) under control conditions and in response to an elevation in sodium intake; genetic linkage analysis was performed in an F2 population (n=219) derived from these strains. Basal renal P4504A enzyme activity measured by conversion of [14C]arachidonic acid to 20-hydroxyeicosatetraenoic acid (20-HETE) was significantly greater in the kidneys of adult SHR (n=7) than of BN (n=8) (82±7 versus 60±5 pmol/min per milligram protein). Renal 20-HETE production fell 45% in SHR and 22% in BN in which salt intake was elevated by drinking of saline instead of water for 2 weeks. Mean arterial pressure averaged 157±3 mm Hg in SHR (n=9) and 100±2 mm Hg in BN fed a normal salt diet, and it rose to 170±7 mm Hg (P<.05) in SHR and fell to 90±3 mm Hg (P<.05) in BN (n=8) after sodium intake was elevated. A polymorphic marker, D5Rjr1, that spanned a repeated element in the P4504A1 gene on chromosome 5, where all three P4504A isoforms are located, was used for genotyping of the F2 population. The P4504A genotype did not cosegregate with baseline mean arterial pressure in the F2 population; however, significant linkage was observed with the change in mean arterial pressure after sodium intake of the rats was elevated. The degree of linkage differed in male and female rats, and the highest LOD score (3.6) was observed in male F2 rats with a BN grandfather. These findings suggest that the difference in renal P450 activity in SHR and BN does not contribute to the development of hypertension in this F2 population, but it may play some role in determining the blood pressure response to an elevation in salt intake.
Key Words: hydroxyeicosatetraenoic acids • rats, inbred strains • sodium, dietary • genotype • cytochrome P450
This article has been cited by other articles:
 |
|
 |
|
  K. M. Dunn, M. Renic, A. K. Flasch, D. R. Harder, J. Falck, and R. J. Roman Elevated production of 20-HETE in the cerebral vasculature contributes to severity of ischemic stroke and oxidative stress in spontaneously hypertensive rats Am J Physiol Heart Circ Physiol, December 1, 2008; 295(6): H2455 - H2465. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Morin, M. Sirois, V. Echave, M. M. Gomes, and E. Rousseau Functional effects of 20-HETE on human bronchi: hyperpolarization and relaxation due to BKCa channel activation Am J Physiol Lung Cell Mol Physiol, October 1, 2007; 293(4): L1037 - L1044. [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]
|
|
|
|
 |
|
 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]
|
|
|
|
|
|
X. Zhao, D. M. Pollock, D. C. Zeldin, and J. D. Imig Salt-Sensitive Hypertension After Exposure to Angiotensin Is Associated With Inability to Upregulate Renal Epoxygenases Hypertension, October 1, 2003; 42(4): 775 - 780. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Cloutier, S. Campbell, N. Basora, S. Proteau, M. D. Payet, and E. Rousseau 20-HETE inotropic effects involve the activation of a nonselective cationic current in airway smooth muscle Am J Physiol Lung Cell Mol Physiol, September 1, 2003; 285(3): L560 - L568. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Zhao, D. M. Pollock, E. W. Inscho, D. C. Zeldin, and J. D. Imig Decreased Renal Cytochrome P450 2C Enzymes and Impaired Vasodilation Are Associated With Angiotensin Salt-Sensitive Hypertension Hypertension, March 1, 2003; 41(3): 709 - 714. [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]
|
|
|
|
|
|
M. Alonso-Galicia, K. G. Maier, A. S. Greene, A. W. Cowley Jr., and R. J. Roman Role of 20-hydroxyeicosatetraenoic acid in the renal and vasoconstrictor actions of angiotensin II Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2002; 283(1): R60 - R68. [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]
|
|
|
|
|
|
O. Ito, K. Omata, S. Ito, K. M. Hoagland, and R. J. Roman Effects of converting enzyme inhibitors on renal P-450 metabolism of arachidonic acid Am J Physiol Regulatory Integrative Comp Physiol, March 1, 2001; 280(3): R822 - R830. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Gu, Y. Wei, H. Jiang, M. Balazy, and W. Wang Role of 20-HETE in mediating the effect of dietary K intake on the apical K channels in the mTAL Am J Physiol Renal Physiol, February 1, 2001; 280(2): F223 - F230. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. R. Jacobs and D. C. Zeldin The lung HETEs (and EETs) up Am J Physiol Heart Circ Physiol, January 1, 2001; 280(1): H1 - H10. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Yu, L. M. Huse, P. Adler, L. Graham, J. Ma, D. C. Zeldin, and D. L. Kroetz Increased CYP2J Expression and Epoxyeicosatrienoic Acid Formation in Spontaneously Hypertensive Rat Kidney Mol. Pharmacol., May 1, 2000; 57(5): 1011 - 1020. [Abstract] [Full Text]
|
|
|
|
 |
|
 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. P. Rapp Genetic Analysis of Inherited Hypertension in the Rat Physiol Rev, January 1, 2000; 80(1): 135 - 172. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Alonso-Galicia, J. R. Falck, K. M. Reddy, and R. J. Roman 20-HETE agonists and antagonists in the renal circulation Am J Physiol Renal Physiol, November 1, 1999; 277(5): F790 - F796. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Zicha and J. Kunes Ontogenetic Aspects of Hypertension Development: Analysis in the Rat Physiol Rev, October 1, 1999; 79(4): 1227 - 1282. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Ma, W. Qu, P. E. Scarborough, K. B. Tomer, C. R. Moomaw, R. Maronpot, L. S. Davis, M. D. Breyer, and D. C. Zeldin Molecular Cloning, Enzymatic Characterization, Developmental Expression, and Cellular Localization of a Mouse Cytochrome P450 Highly Expressed in Kidney J. Biol. Chem., June 18, 1999; 274(25): 17777 - 17788. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Nguyen, M.-H. Wang, K. M. Reddy, J. R. Falck, and M. L. Schwartzman Kinetic profile of the rat CYP4A isoforms: arachidonic acid metabolism and isoform-specific inhibitors Am J Physiol Regulatory Integrative Comp Physiol, June 1, 1999; 276(6): R1691 - R1700. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
R. F. Husted, J. P. Rapp, and J. B. Stokes Candidate Genes in the Regulation of Na+ Transport by Inner Medullary Collecting Duct Cells From Dahl Rats Hypertension, February 1, 1998; 31(2): 608 - 614. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. L. Kroetz, L. M. Huse, A. Thuresson, and M. P. Grillo Developmentally Regulated Expression of the CYP4A Genes in the Spontaneously Hypertensive Rat Kidney Mol. Pharmacol., September 1, 1997; 52(3): 362 - 372. [Abstract] [Full Text]
|
|
|
|
|
|
C. J. Sinal, M. Miyata, M. Tohkin, K. Nagata, J. R. Bend, and F. J. Gonzalez Targeted Disruption of Soluble Epoxide Hydrolase Reveals a Role in Blood Pressure Regulation J. Biol. Chem., December 15, 2000; 275(51): 40504 - 40510. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. R. Garrett and J. P. Rapp Two closely linked interactive blood pressure QTL on rat chromosome 5 defined using congenic Dahl rats Physiol Genomics, February 28, 2002; 8(2): 81 - 86. [Abstract] [Full Text] [PDF]
|
|