(Hypertension. 1997;29:320.)
© 1997 American Heart Association, Inc.
Arthur C. Corcoran Memorial Lecture |
From the Department of Physiology, Medical College of Wisconsin, Milwaukee (M.A.-G., H.A.D., R.J.D.); and the Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas (K.K.R., J.R.F.).
Correspondence to Dr Richard J. Roman, Department of Physiology, Medical College of Wisconsin, 8701 Watertown Plank Rd, Milwaukee, WI 53226-0509. E-mail rroman{at}post.its.mcw.edu
Nitric oxide (NO) inhibits a variety of heme-containing enzymes, including NO synthase and cytochrome P4501A1 and 2B1. The present study examined whether NO inhibits the production of 20-hydroxyeicosatetraenoic acid (20-HETE) by cytochrome P4504A enzymes and whether blockade of the production of this substance contributes to the vascular effects of NO. Sodium nitroprusside (SNP; 10-5, 10-4, and 10-3 mol/L) reduced the production of 20-HETE by renal microsomes incubated with arachidonic acid to 71±5%, 29±4%, and 4±2% of control, respectively (n=5). Similar results were obtained with the use of 1-propanamine, 3-(2-hydroxy-2-nitroso-1-propylhydrazino) (n=3). To determine whether inhibition of 20-HETE contributes to the vasodilatory effects of NO, the effects of dibromo-dodecenyl-methylsulfimide (DDMS), a selective inhibitor of the formation of 20-HETE, on the response to SNP (10-7 to 10-3 mol/L) were examined in rat renal arterioles preconstricted with phenylephrine (n=5). SNP increased vascular diameter in a concentration-dependent manner to 82±4% of control. After DDMS (25 µmol/L), SNP (10-3 mol/L) increased vascular diameter by only 17±3%. The effects of DDMS on the mean arterial pressure (MAP) and renal blood flow (RBF) responses to infusion of an NO donor and a synthase inhibitor were also examined in thiobutabarbital-anesthetized, Sprague-Dawley rats. Infusion of MAHMA NONOate at 1, 3, 5, and 10 nmol/min reduced MAP by 16±2, 30±3, 40±5, and 48±5 mm Hg and lowered renal vascular resistance (RVR) by 15±3%, 26±2%, 30±3%, and 34±4% of control. After DDMS (10 mg/kg, n=7 rats), the MAP and RVR responses to 1-hexamine, 6-(2-hydroxy-1-methyl-2-nitrohydrazino)N-methyl (MAHMA NONOate) averaged only 20% of those seen during control. In other experiments, MAP increased by 32±4% and RBF fell to 56±5% of control after administration of N-nitro-L-arginine (L-NArg) (10 mg/kg IV). After DDMS (10 mg/kg, n=7 rats), MAP increased by only 19±4% and RBF fell by only 7±4% after L-NArg. These results indicate that NO inhibits cytochrome P4504A enzymes and that inhibition of the production of 20-HETE contributes to the vasodilatory effects of NO.
Key Words: nitric oxide vasculature enzymes
Abbreviations: AA = arachidonic acid DDMS = dibromo-dodecenyl-methylsulfimide DiHETEs = dihydroxyeicosatetraenoic acids EETs = eicosatrienoic acids 20-HETE = 20-hydroxyeicosatetraenoic acid HPLC = high-performance liquid chromatography L-NArg = N-nitro-L-arginine MAHMA NONate = 1-hexamine, 6-(2-hydroxy-1-methyl-2-nitrosohydrazino)N-methyl MAP = mean arterial pressure NO = nitric oxide 17-ODYA = 17-octadecynoic acid PAPA NONOate = 1-propanamine, 3-(2-hydroxy-2-nitroso-1-propylhydrazino) RBF = renal blood flow SNP = sodium nitroprusside
This article has been cited by other articles:
![]() |
X. Liu, C. Li, J. R. Falck, R. J. Roman, D. R. Harder, and R. C. Koehler Interaction of nitric oxide, 20-HETE, and EETs during functional hyperemia in whisker barrel cortex Am J Physiol Heart Circ Physiol, August 1, 2008; 295(2): H619 - H631. [Abstract] [Full Text] [PDF] |
||||
![]() |
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] |
||||
![]() |
P. J. Marvar, J. R. Falck, and M. A. Boegehold High dietary salt reduces the contribution of 20-HETE to arteriolar oxygen responsiveness in skeletal muscle Am J Physiol Heart Circ Physiol, March 1, 2007; 292(3): H1507 - H1515. [Abstract] [Full Text] [PDF] |
||||
![]() |
F. Vargas, J. M. Moreno, R. Wangensteen, I. Rodriguez-Gomez, and J. Garcia-Estan The endocrine system in chronic nitric oxide deficiency Eur. J. Endocrinol., January 1, 2007; 156(1): 1 - 12. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Wendel, L. Knels, W. Kummer, and T. Koch Distribution of Endothelin Receptor Subtypes ETA and ETB in the Rat Kidney J. Histochem. Cytochem., November 1, 2006; 54(11): 1193 - 1203. [Abstract] [Full Text] [PDF] |
||||
![]() |
E. R. Jacobs, D. Zhu, S. Gruenloh, B. Lopez, and M. Medhora VEGF-induced relaxation of pulmonary arteries is mediated by endothelial cytochrome P-450 hydroxylase Am J Physiol Lung Cell Mol Physiol, September 1, 2006; 291(3): L369 - L377. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Guo, R. J. Roman, J. D. Fenstermacher, S. L. Brown, J. R. Falck, A. S. Arbab, P. A. Edwards, and A. G. Scicli 9L Gliosarcoma Cell Proliferation and Tumor Growth in Rats Are Suppressed by N-Hydroxy-N'-(4-butyl-2-methylphenol) Formamidine (HET0016), a Selective Inhibitor of CYP4A J. Pharmacol. Exp. Ther., April 1, 2006; 317(1): 97 - 108. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. Bellien, R. Joannides, M. Iacob, P. Arnaud, and C. Thuillez Evidence for a basal release of a cytochrome-related endothelium-derived hyperpolarizing factor in the radial artery in humans Am J Physiol Heart Circ Physiol, April 1, 2006; 290(4): H1347 - H1352. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. Andresen, N. I. Shafi, and R. M. Bryan Jr. Endothelial influences on cerebrovascular tone J Appl Physiol, January 1, 2006; 100(1): 318 - 327. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. Huang, Y. Zhou, V. T. Raju, J. Du, H.-H. Chang, C.-Y. Wang, M. W. Brands, J. R. Falck, and M.-H. Wang Renal 20-HETE inhibition attenuates changes in renal hemodynamics induced by L-NAME treatment in pregnant rats Am J Physiol Renal Physiol, November 1, 2005; 289(5): F1116 - F1122. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. A. Parker, T. R. Grover, J. P. Kinsella, J. R. Falck, and S. H. Abman Inhibition of 20-HETE abolishes the myogenic response during NOS antagonism in the ovine fetal pulmonary circulation Am J Physiol Lung Cell Mol Physiol, August 1, 2005; 289(2): L261 - L267. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. Yang, J. W. Clark, R. M. Bryan, and C. S. Robertson Mathematical modeling of the nitric oxide/cGMP pathway in the vascular smooth muscle cell Am J Physiol Heart Circ Physiol, August 1, 2005; 289(2): H886 - H897. [Abstract] [Full Text] [PDF] |
||||
![]() |
O. Jung, R. P. Brandes, I.-H. Kim, F. Schweda, R. Schmidt, B. D. Hammock, R. Busse, and I. Fleming Soluble Epoxide Hydrolase Is a Main Effector of Angiotensin II-Induced Hypertension Hypertension, April 1, 2005; 45(4): 759 - 765. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. D. Baines and P. Ho 20-HETE-mediated vasoconstriction by hemoglobin-O2 carrier in Sprague-Dawley but not Wistar rats J Appl Physiol, March 1, 2005; 98(3): 772 - 779. [Abstract] [Full Text] [PDF] |
||||
![]() |
V. Randriamboavonjy, L. Kiss, J. R. Falck, R. Busse, and I. Fleming The synthesis of 20-HETE in small porcine coronary arteries antagonizes EDHF-mediated relaxation Cardiovasc Res, February 1, 2005; 65(2): 487 - 494. [Abstract] [Full Text] [PDF] |
||||
![]() |
N. C. Ward, J. Rivera, J. Hodgson, I. B. Puddey, L. J. Beilin, J. R. Falck, and K. D. Croft Urinary 20-Hydroxyeicosatetraenoic Acid Is Associated With Endothelial Dysfunction in Humans Circulation, July 27, 2004; 110(4): 438 - 443. [Abstract] [Full Text] [PDF] |
||||
![]() |
G. O. Ogungbade, L. A. Akinsanmi, H. Jiang, and A. O. Oyekan Role of epoxyeicosatrienoic acids in renal functional response to inhibition of NO production in the rat Am J Physiol Renal Physiol, November 1, 2003; 285(5): F955 - F964. [Abstract] [Full Text] [PDF] |
||||
![]() |
I. T. Udosen, H. Jiang, H. C. Hercule, and A. O. Oyekan Nitric oxide-epoxygenase interactions and arachidonate-induced dilation of rat renal microvessels Am J Physiol Heart Circ Physiol, November 1, 2003; 285(5): H2054 - H2063. [Abstract] [Full Text] [PDF] |
||||
![]() |
I. Fleming Brain in the Brawn: The Neuronal Nitric Oxide Synthase as a Regulator of Myogenic Tone Circ. Res., October 3, 2003; 93(7): 586 - 588. [Full Text] [PDF] |
||||
![]() |
J. Quilley, Y. Qiu, and J. Hirt Inhibitors of 20-Hydroxyeicosatetraenoic Acid Reduce Renal Vasoconstrictor Responsiveness J. Pharmacol. Exp. Ther., October 1, 2003; 307(1): 223 - 229. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. He, T. Podymow, J. Zimpelmann, and K. D. Burns NO inhibits Na+-K+-2Cl- cotransport via a cytochrome P-450-dependent pathway in renal epithelial cells (MMDD1) Am J Physiol Renal Physiol, June 1, 2003; 284(6): F1235 - F1244. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Yu, R. P. McAndrew, R. Al-Saghir, K. G. Maier, M. Medhora, R. J. Roman, and E. R. Jacobs Nitric oxide contributes to 20-HETE-induced relaxation of pulmonary arteries J Appl Physiol, October 1, 2002; 93(4): 1391 - 1399. [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] |
||||
![]() |
E. T. Morgan, V. Ullrich, A. Daiber, P. Schmidt, N. Takaya, H. Shoun, J. C. McGiff, A. Oyekan, C. J. Hanke, W. B. Campbell, et al. Cytochromes P450 and Flavin Monooxygenases---Targets and Sources of Nitric Oxide Drug Metab. Dispos., November 1, 2001; 29(11): 1366 - 1376. [Abstract] [Full Text] [PDF] |
||||
![]() |
I. Fleming Cytochrome P450 and Vascular Homeostasis Circ. Res., October 26, 2001; 89(9): 753 - 762. [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] |
||||
![]() |
P. S. Andrew, Y. Deng, R. Sultanian, and S. Kaufman Nitric oxide increases fluid extravasation from the splenic circulation of the rat Am J Physiol Regulatory Integrative Comp Physiol, April 1, 2001; 280(4): R959 - R967. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. P. Kunert, R. J. Roman, M. Alonso-Galicia, J. R. Falck, and J. H. Lombard Cytochrome P-450 {omega}-hydroxylase: a potential O2 sensor in rat arterioles and skeletal muscle cells Am J Physiol Heart Circ Physiol, April 1, 2001; 280(4): H1840 - H1845. [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] |
||||
![]() |
J. C. Frisbee, R. J. Roman, U. M. Krishna, J. R. Falck, and J. H. Lombard 20-HETE modulates myogenic response of skeletal muscle resistance arteries from hypertensive Dahl-SS rats Am J Physiol Heart Circ Physiol, March 1, 2001; 280(3): H1066 - H1074. [Abstract] [Full Text] [PDF] |
||||
![]() |
V. B. O'Donnell and B. A. Freeman Interactions Between Nitric Oxide and Lipid Oxidation Pathways : Implications for Vascular Disease Circ. Res., January 19, 2001; 88(1): 12 - 21. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. C. Hercule and A. O. Oyekan Role of NO and cytochrome P-450-derived eicosanoids in ET-1-induced changes in intrarenal hemodynamics in rats Am J Physiol Regulatory Integrative Comp Physiol, December 1, 2000; 279(6): R2132 - R2141. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. D. Imig Eicosanoid regulation of the renal vasculature Am J Physiol Renal Physiol, December 1, 2000; 279(6): F965 - F981. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. A Carroll and J. C McGiff A new class of lipid mediators: cytochrome P450 arachidonate metabolites Thorax, October 1, 2000; 55(90002): 13S - 16. [Full Text] |
||||
![]() |
J.-Z. Yu, D. X. Zhang, A.-P. Zou, W. B. Campbell, and P.-L. Li Nitric oxide inhibits Ca2+ mobilization through cADP-ribose signaling in coronary arterial smooth muscle cells Am J Physiol Heart Circ Physiol, September 1, 2000; 279(3): H873 - H881. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. Gebremedhin, A. R. Lange, T. F. Lowry, M. R. Taheri, E. K. Birks, A. G. Hudetz, J. Narayanan, J. R. Falck, H. Okamoto, R. J. Roman, et al. Production of 20-HETE and Its Role in Autoregulation of Cerebral Blood Flow Circ. Res., July 7, 2000; 87(1): 60 - 65. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Bloodsworth, V. B. O'Donnell, and B. A. Freeman Nitric Oxide Regulation of Free Radical- and Enzyme-Mediated Lipid and Lipoprotein Oxidation Arterioscler. Thromb. Vasc. Biol., July 1, 2000; 20(7): 1707 - 1715. [Abstract] [Full Text] [PDF] |
||||
![]() |
C.-W. Sun, J. R. Falck, H. Okamoto, D. R. Harder, and R. J. Roman Role of cGMP versus 20-HETE in the vasodilator response to nitric oxide in rat cerebral arteries Am J Physiol Heart Circ Physiol, July 1, 2000; 279(1): H339 - H350. [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. Geiger, A.-P. Zou, W. B. Campbell, and P.-L. Li Inhibition of cADP-Ribose Formation Produces Vasodilation in Bovine Coronary Arteries Hypertension, January 1, 2000; 35(1): 397 - 402. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Alonso-Galicia, A. G. Hudetz, H. Shen, D. R. Harder, R. J. Roman, and H. A. Kontos Contribution of 20-HETE to Vasodilator Actions of Nitric Oxide in the Cerebral Microcirculation • Editorial Comment Stroke, December 1, 1999; 30(12): 2727 - 2734. [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. C. McGiff and J. Quilley 20-HETE and the kidney: resolution of old problems and new beginnings Am J Physiol Regulatory Integrative Comp Physiol, September 1, 1999; 277(3): R607 - R623. [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] |
||||
![]() |
W. G. Mayhan VEGF increases permeability of the blood-brain barrier via a nitric oxide synthase/cGMP-dependent pathway Am J Physiol Cell Physiol, May 1, 1999; 276(5): C1148 - C1153. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. H. Lombard, M. P. Kunert, R. J. Roman, J. R. Falck, D. R. Harder, and W. F. Jackson Cytochrome P-450 omega -hydroxylase senses O2 in hamster muscle, but not cheek pouch epithelium, microcirculation Am J Physiol Heart Circ Physiol, February 1, 1999; 276(2): H503 - H508. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. K. Bradley, I. L. O. Buxton, J. E. Barber, T. McGaw, and M. E. Bradley Nitric oxide relaxes human myometrium by a cGMP-independent mechanism Am J Physiol Cell Physiol, December 1, 1998; 275(6): C1668 - C1673. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Koller, G. Dornyei, and G. Kaley Flow-induced responses in skeletal muscle venules: modulation by nitric oxide and prostaglandins Am J Physiol Heart Circ Physiol, September 1, 1998; 275(3): H831 - H836. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Alonso-Galicia, C.-W. Sun, J. R. Falck, D. R. Harder, and R. J. Roman Contribution of 20-HETE to the vasodilator actions of nitric oxide in renal arteries Am J Physiol Renal Physiol, September 1, 1998; 275(3): F370 - F378. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. Zhu, R. M. Effros, D. R. Harder, R. J. Roman, and E. R. Jacobs Tissue Sources of Cytochrome P450 4A and 20-HETE Synthesis in Rabbit Lungs Am. J. Respir. Cell Mol. Biol., July 1, 1998; 19(1): 121 - 128. [Abstract] [Full Text] |
||||
![]() |
A. Ichihara, J. D. Imig, E. W. Inscho, and L. G. Navar Interactive Nitric Oxide–Angiotensin II Influences on Renal Microcirculation in Angiotensin II–Induced Hypertension Hypertension, June 1, 1998; 31(6): 1255 - 1260. [Abstract] [Full Text] [PDF] |
||||
![]() |
M.-H. Wang, E. Brand-Schieber, B. A. Zand, X. Nguyen, J. R. Falck, N. Balu, and M. L. Schwartzman Cytochrome P450-Derived Arachidonic Acid Metabolism in the Rat Kidney: Characterization of Selective Inhibitors J. Pharmacol. Exp. Ther., March 1, 1998; 284(3): 966 - 973. [Abstract] [Full Text] |
||||
![]() |
A. Ichihara, E. W. Inscho, J. D. Imig, and L. G. Navar Neuronal nitric oxide synthase modulates rat renal microvascular function Am J Physiol Renal Physiol, March 1, 1998; 274(3): F516 - F524. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. R. Uddin, M. M. Muthalif, N. A. Karzoun, I. F. Benter, and K. U. Malik Cytochrome P-450 Metabolites Mediate Norepinephrine-Induced Mitogenic Signaling Hypertension, January 1, 1998; 31(1): 242 - 247. [Abstract] [Full Text] [PDF] |
||||
![]() |
|