Role of Vascular Reactive Oxygen Species in Regulating Cytochrome P450-4A Enzyme Expression in Dahl Salt-sensitive Rats

Overview

Journal Microcirculation

Specialties Biology
Cardiology & Vascular Diseases

Date 2016 Aug 19

PMID 27537772

Citations 7

Authors

Kathleen M Lukaszewicz

Mahesh P Paudyal

John R Falck

Julian H Lombard

Affiliations

Soon will be listed here.

Abstract

Objective: The potential contribution of CYP4A enzymes to endothelial dysfunction in Dahl salt-sensitive rats was determined by comparison to SS-5 consomic rats having chromosome 5 carrying CYP4A alleles from the BN rat introgressed into the SS genetic background.

Methods: The following experiments were performed in cerebral arteries from HS-fed SS and SS-5 rats ± the SOD inhibitor DETC and/or the superoxide scavenger Tempol: (i) endothelial function was determined via video microscopy ± acute addition of the CYP4A inhibitor DDMS or Tempol; (ii) vascular oxidative stress was assessed with DHE fluorescence ± acute addition of DDMS, l-NAME, or PEG-SOD; and (iii) CYP4A protein levels were compared by western blotting.

Results: In DETC-treated SS-5 and HS-fed SS rats, (i) DDMS or Tempol ameliorated vascular dysfunction, (ii) DDMS reduced vascular oxidative stress to control levels, (iii) chronic Tempol treatment reduced vascular CYP4A protein expression, and (iv) combined treatment with Tempol and l-NAME prevented the reduction in CYP4A protein expression in MCA of HS-fed SS rats.

Conclusion: The CYP4A pathway plays a role in vascular dysfunction in SS rats and there appears to be a direct role of reduced NO availability due to salt-induced oxidant stress in upregulating CYP4A enzyme expression.

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References

Hoagland K, Maier K, Roman R . Contributions of 20-HETE to the antihypertensive effects of Tempol in Dahl salt-sensitive rats. Hypertension. 2003; 41(3 Pt 2):697-702. DOI: 10.1161/01.HYP.0000047881.15426.DC. View

Singh H, Cheng J, Deng H, Kemp R, Ishizuka T, Nasjletti A . Vascular cytochrome P450 4A expression and 20-hydroxyeicosatetraenoic acid synthesis contribute to endothelial dysfunction in androgen-induced hypertension. Hypertension. 2007; 50(1):123-9. DOI: 10.1161/HYPERTENSIONAHA.107.089599. View

Ischiropoulos H, Zhu L, Chen J, Tsai M, Martin J, Smith C . Peroxynitrite-mediated tyrosine nitration catalyzed by superoxide dismutase. Arch Biochem Biophys. 1992; 298(2):431-7. DOI: 10.1016/0003-9861(92)90431-u. View

Cheng J, Wu C, Gotlinger K, Zhang F, Falck J, Narsimhaswamy D . 20-hydroxy-5,8,11,14-eicosatetraenoic acid mediates endothelial dysfunction via IkappaB kinase-dependent endothelial nitric-oxide synthase uncoupling. J Pharmacol Exp Ther. 2009; 332(1):57-65. PMC: 2802478. DOI: 10.1124/jpet.109.159863. View

Wang J, Maier K, Roman R, Cruz L, Zhu J, Henderson L . Expression of cytochrome P450-4A isoforms in the rat cremaster muscle microcirculation. Microcirculation. 2004; 11(1):89-96. DOI: 10.1080/10739680490266225. View

Capdevila J, Parkhill L, Chacos N, Okita R, Masters B, Estabrook R . The oxidative metabolism of arachidonic acid by purified cytochromes P-450. Biochem Biophys Res Commun. 1981; 101(4):1357-63. DOI: 10.1016/0006-291x(81)91597-7. View

Meng S, Roberts 2nd L, Cason G, Curry T, Manning Jr R . Superoxide dismutase and oxidative stress in Dahl salt-sensitive and -resistant rats. Am J Physiol Regul Integr Comp Physiol. 2002; 283(3):R732-8. DOI: 10.1152/ajpregu.00346.2001. View

Brzezinska A, Gebremedhin D, Chilian W, Kalyanaraman B, Elliott S . Peroxynitrite reversibly inhibits Ca(2+)-activated K(+) channels in rat cerebral artery smooth muscle cells. Am J Physiol Heart Circ Physiol. 2000; 278(6):H1883-90. DOI: 10.1152/ajpheart.2000.278.6.H1883. View

Rao G, Berk B . Active oxygen species stimulate vascular smooth muscle cell growth and proto-oncogene expression. Circ Res. 1992; 70(3):593-9. DOI: 10.1161/01.res.70.3.593. View

10.

Cosentino F, Sill J, Katusic Z . Role of superoxide anions in the mediation of endothelium-dependent contractions. Hypertension. 1994; 23(2):229-35. DOI: 10.1161/01.hyp.23.2.229. View

11.

Priestley J, Buelow M, McEwen S, Weinberg B, Delaney M, Balus S . Reduced angiotensin II levels cause generalized vascular dysfunction via oxidant stress in hamster cheek pouch arterioles. Microvasc Res. 2013; 89:134-45. PMC: 3758804. DOI: 10.1016/j.mvr.2013.04.004. View

12.

Khatsenko O, Boobis A, Gross S . Evidence for nitric oxide participation in down-regulation of CYP2B1/2 gene expression at the pretranslational level. Toxicol Lett. 1997; 90(2-3):207-16. DOI: 10.1016/s0378-4274(96)03857-x. View

13.

Faraci F, Didion S . Vascular protection: superoxide dismutase isoforms in the vessel wall. Arterioscler Thromb Vasc Biol. 2004; 24(8):1367-73. DOI: 10.1161/01.ATV.0000133604.20182.cf. View

14.

Zhu J, Drenjancevic-Peric I, McEwen S, Friesema J, Schulta D, Yu M . Role of superoxide and angiotensin II suppression in salt-induced changes in endothelial Ca2+ signaling and NO production in rat aorta. Am J Physiol Heart Circ Physiol. 2006; 291(2):H929-38. DOI: 10.1152/ajpheart.00692.2005. View

15.

Zeng Q, Han Y, Bao Y, Li W, Li X, Shen X . 20-HETE increases NADPH oxidase-derived ROS production and stimulates the L-type Ca2+ channel via a PKC-dependent mechanism in cardiomyocytes. Am J Physiol Heart Circ Physiol. 2010; 299(4):H1109-17. PMC: 2957347. DOI: 10.1152/ajpheart.00067.2010. View

16.

Zafari A, Ushio-Fukai M, Akers M, Yin Q, Shah A, Harrison D . Role of NADH/NADPH oxidase-derived H2O2 in angiotensin II-induced vascular hypertrophy. Hypertension. 1998; 32(3):488-95. DOI: 10.1161/01.hyp.32.3.488. View

17.

Fredricks K, Liu Y, Lombard J . Response of extraparenchymal resistance arteries of rat skeletal muscle to reduced PO2. Am J Physiol. 1994; 267(2 Pt 2):H706-15. DOI: 10.1152/ajpheart.1994.267.2.H706. View

18.

Mattson D, Dwinell M, Greene A, Kwitek A, Roman R, Jacob H . Chromosome substitution reveals the genetic basis of Dahl salt-sensitive hypertension and renal disease. Am J Physiol Renal Physiol. 2008; 295(3):F837-42. PMC: 2536867. DOI: 10.1152/ajprenal.90341.2008. View

19.

Chen W, Druhan L, Chen C, Hemann C, Chen Y, Berka V . Peroxynitrite induces destruction of the tetrahydrobiopterin and heme in endothelial nitric oxide synthase: transition from reversible to irreversible enzyme inhibition. Biochemistry. 2010; 49(14):3129-37. PMC: 2851177. DOI: 10.1021/bi9016632. View

20.

Drenjancevic-Peric I, Lombard J . Introgression of chromosome 13 in Dahl salt-sensitive genetic background restores cerebral vascular relaxation. Am J Physiol Heart Circ Physiol. 2004; 287(2):H957-62. DOI: 10.1152/ajpheart.01087.2003. View