AJP - Heart BIOPAC complete lab solutions
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Am J Physiol Heart Circ Physiol 291: H1999-H2002, 2006. First published June 23, 2006; doi:10.1152/ajpheart.00082.2006
0363-6135/06 $8.00
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
291/4/H1999    most recent
00082.2006v2
00082.2006v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Web of Science (3)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Sacerdoti, D.
Right arrow Articles by Abraham, N. G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Sacerdoti, D.
Right arrow Articles by Abraham, N. G.

Rat mesenteric arterial dilator response to 11,12-epoxyeicosatrienoic acid is mediated by activating heme oxygenase

David Sacerdoti,1 Massimo Bolognesi,1 Marco Di Pascoli,1 Angelo Gatta,1 John C. McGiff,2 Michal Laniado Schwartzman,2 and Nader G. Abraham2

1Department of Clinical and Experimental Medicine, Clinica Medica 5, University of Padova, Padova, Italy; and 2Department of Pharmacology, New York Medical College, Valhalla, New York

Submitted 19 January 2006 ; accepted in final form 30 May 2006


   ABSTRACT
TOP
 ABSTRACT
MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 GRANTS
 REFERENCES
 
11,12-Epoxyeicosatrienoic acid (11,12-EET), a potent vasodilator produced by the endothelium, acts on calcium-activated potassium channels and shares biological activities with the heme oxygenase/carbon monoxide (HO/CO) system. We examined whether activation of HO mediates the dilator action of 11,12-EET, and that of the other EETs, on rat mesenteric arteries. Dose-response curves (10–9 to 10–6 M) to 5,6-EET, 8,9-EET, 11,12-EET, 14,15-EET, and ACh (10–9 to 10–4 M) were evaluated in preconstricted (10–6 mol/l phenylephrine) mesenteric arteries (<350 µm diameter) in the presence or absence of 1) the cyclooxygenase inhibitor indomethacin (2.8 µM), 2) the HO inhibitor chromium mesoporphyrin (CrMP) (15 µM), 3) the soluble guanylyl cyclase (GC) inhibitor ODQ (10 µM), and 4) the calcium-activated potassium channel inhibitor iberiotoxin (25 nM). The vasodilator response to 11,12-EET was abolished by CrMP and iberiotoxin, whereas indomethacin and ODQ had no effect. In contrast, the effect of ACh was attenuated by ODQ but not by CrMP. The vasodilator effect of 8,9-EET, like that of 11,12-EET, was greatly attenuated by HO inhibition. In contrast, the mesenteric vasodilator response to 5,6-EET was independent of both HO and GC, whereas that to 14,15-EET demonstrated two components, an HO and a GC, of equal magnitude. Incubation of mesenteric microvessels with 11,12-EET caused a 30% increase in CO release, an effect abolished by inhibition of HO. We conclude that the rat mesenteric vasodilator action of 11,12-EET is mediated via an increase in HO activity and an activation of calcium-activated potassium channels.

epoxygenase; carbon monoxide; endothelial cell; mesenteric artery

ARACHIDONIC ACID can be metabolized in endothelial cells (21) by epoxygenases to four epoxyeicosatrienoic acids (EETs): 5,6-EET, 8,9-EET, 11,12-EET, and 14,15-EET (23, 29). The 11,12-EET exhibits diverse biological activities, including dilation of preglomerular microvessels (7, 12), stimulation of angiogenesis (16), and inhibition of sodium transport (27). Additionally, 11,12-EET demonstrates anti-inflammatory properties, e.g., inhibition of adhesion molecule expression in response to inflammatory mediators (19), and contributes to opposing elevation of blood pressure in response to salt loading (15). The 11,12-EET has also been proposed to act as an endothelial-derived hyperpolarizing factor by activating calcium-activated potassium channels (KCa) (3, 5, 9). Carbon monoxide (CO), generated by the heme oxygenase (HO) system, also activates potassium channels (14), dilates arteries (24, 30), and exhibits anti-inflammatory (2, 24) and antihypertensive properties (22, 30). Furthermore, both EETs (28) and the HO/CO system attenuate ischemic injury (25).

Because EETs, particularly 11,12-EET, and the HO system share overlapping biological activities, we examined a possible link between 11,12-EET and HO activity in the regulation of vascular tone in rat mesenteric microvessels. We report here that 11,12-EET dilated rat mesenteric arteries via an HO-dependent mechanism, acting through KCa channels. The 5,6-EET, 8,9-EET, and 14,15-EET vasodilated mesenteric arteries. However, only 8,9-EET acted through a mechanism similar to that of 11,12-EET, whereas the 5,6-EET vasodilator effect was independent of HO and guanylyl cyclase and the effect of 14,15-EET was only partly reduced by chromium mesoporphyrin (CrMP).


   MATERIALS AND METHODS
TOP
 ABSTRACT
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 GRANTS
 REFERENCES
 
Chemicals. CrMP was obtained from Porphyrin Products (Logan, UT), and 5,6-, 8,9-, 11,12, and 14,15-EET were from Cayman Chemical (Ann Arbor, MI). All other chemicals were obtained from Sigma (St. Louis, MO). ACh was dissolved in deionized water and diluted with Krebs buffer. CrMP was dissolved in a solution of 50 mM NaCO3. Indomethacin was dissolved in ethanol and diluted with Krebs buffer. CORM-3 was a generous gift from Dr. J. R. Falck and was dissolved in water and then in Krebs buffer.

Mesenteric microvessels. The study was performed on adult male Wistar rats (Charles River, Calco, Italy), with body weights of 200–225 g. The third- and fourth-order branches of the superior mesenteric artery (<350 µm in diameter, 1–2 mm in length) were removed from the mesenteric vascular bed (4, 21) and mounted on glass micropipettes in a water-jacketed perfusion chamber (Living Systems Instrumentation, Burlington, VT) in warmed (37°C), oxygenated (95% O2-5% CO2) Krebs-Henseleit buffer solution. The vessels were mounted on a micropipette connected to a pressure servo controller. Subsequently, the lumen of the vessel was flushed to remove residual blood, and the end of the vessel was mounted on a micropipette connected to a three-way stopcock. The vessel was pressurized to 80 mmHg and superfused with Krebs-Henseleit buffer solution (4 ml/min) at 37°C and gassed with 95% O2-5% CO2. Vascular diameters were measured by a video system, which included a microscope with a CCD television camera (Eclipse TS100-F, Nikon, Tokyo, Japan), a television monitor (Ultrak, Lewisville, TX), and a video measuring system (Living Systems Instrumentation). After 45 min of equilibration, the presence of a functional endothelium was confirmed by relaxation to ACh (10–6 M) after preconstriction with phenylephrine (PE) (10–6 mol/l). Arteries with <50% relaxation of PE-induced contraction were discarded. Vasodilation to increasing 11,12-EET (from 10–9 M to 10–6 M) and ACh (from 10–9 M to 10–4 M) concentrations were investigated in arteries preconstricted with PE (10–6 mol/l), before and after inhibition of HO with CrMP (15 µM), of cyclooxygenase with indomethacin (2.8 µM), of guanylyl cyclase with ODQ (10 µM), and of KCa channels with iberiotoxin (25 nM). Vasodilatation to the CO donor CORM-3 (50–200 µM) was also investigated in arteries preconstricted with PE. CORM-3 was diluted in water and then added to the buffer. All experiments were approved by the Institutional Animal Care and Use Committee and conducted under the Guidelines for the Care and Use of Laboratory Animals published by the Office of Science and Health Reports, National Institutes of Health.

Measurement of HO activity. The effect of 11,12-EET on HO activity was evaluated by incubating mesenteric microvessels with 11,12-EET and measuring CO release. Vessels were incubated at 37°C for 60 min with and without 11,12-EET (10–6 M) and CrMP (15 µM) in amber glass vials (2 ml) containing 1.0 ml of Krebs buffer saturated with 95% O2-5% CO2. The incubations were terminated by placement of the samples in ice. Subsequently, internal standards made of isotopically labeled CO (13C16O and 13C18O) were injected into samples, and the CO content of the headspace gas (expressed as pmol·mg protein–1·60 min–1) was determined by gas chromatography/mass spectroscopy analysis as previously reported (1).

Statistical analyses. The data are presented as the means ± SE. Statistical significance (P < 0.05) among experimental groups was determined by the Fisher method of analysis of multiple comparisons. For comparison among treatment groups, the Null hypothesis was tested by a single-factor ANOVA for multiple groups or unpaired t-test for two groups.


   RESULTS
TOP
 ABSTRACT
 MATERIALS AND METHODS
 RESULTS
DISCUSSION
 GRANTS
 REFERENCES
 
Differential effects of CrMP, ODQ, and iberiotoxin on 11,12-EET-induced vasodilatation. The 11,12-EET caused a dose-dependent increase in diameter (Fig. 1A) of mesenteric arterial segments preconstricted with PE. Indomethacin did not affect the vascular response to 11,12-EET (data not shown). Inhibition of HO with CrMP abolished the vasodilation produced by 11,12-EET (Fig. 1A), suggesting that activation of HO contributes to the mechanism of the vascular action of 11,12-EET. In contrast, the response to ACh was not affected by inhibition of HO with CrMP (Fig. 1B). To address a possible interaction with cGMP, we evaluated the mesenteric arterial response to inhibition of soluble guanylyl cyclase with ODQ. ODQ reduced the vasodilator response to ACh by ~50% (Fig. 1D) but did not affect the response to 11,12-EET (Fig. 1C). To evaluate whether the mesenteric vasodilator action of 11,12-EET was dependent on activation of KCa channels, we determined the ability of the KCa channel inhibitor, iberiotoxin, to affect the vascular response to 11,12-EET. Iberiotoxin (25 nM) abolished the vasodilatation produced by 11,12-EET (Fig. 1E).


Figure 1
View larger version (19K):
[in this window]
[in a new window]
  		Fig. 1. Dose-response effects of 11,12-epoxyeicosatrienoic acid (EET; A) and ACh (B) on mesenteric arterial microvessels preconstricted with phenylephrine (PE) before and after inhibition of heme oxygenase (HO) with chromium mesoporphyrin (CrMP; 15 µM) (A and B), inhibition of guanylyl cyclase with ODQ (10 µM; C and D), and inhibition of calcium-activated potassium (KCa) channel with iberiotoxin (25 nM; E). Results (means ± SE) are expressed as percent decrease in vasoconstriction produced by PE; n = 6. *P < 0.05.

 
Effect of different EETs on mesenteric microvessel tone. We then evaluated the effects of the other EETs on mesenteric microvessels. The 5,6-, 8,9-, and 14–15-EETs caused a dose-dependent increase in diameter of variable magnitude (Fig. 2) of the mesenteric arterial segments preconstricted with PE. CrMP abolished the effect of 8,9-EET (Fig. 2B) and partially inhibited the effect of 14,15-EET (Fig. 2C), but it did not affect vasodilatation to 5,6-EET (Fig. 2A). Furthermore, ODQ did not affect vasodilatation to 5,6-EET (Fig. 2A) and 8,9-EET (Fig. 2B), whereas it decreased the effect of 14,15-EET (Fig. 2C).


Figure 2
View larger version (11K):
[in this window]
[in a new window]
  		Fig. 2. Dose-response effects of 5,6-EET (A), 8,9-EET (B), and 14,15-EET (C) on mesenteric arterial microvessels preconstricted with PE before and after inhibition of HO with CrMP (15 µM) and inhibition of guanylyl cyclase with ODQ (10 µM). Results (means ± SE) are expressed as percent decrease in vasoconstriction produced by PE; n = 4. *P < 0.05.

 
Effect of 11,12-EET on HO activity. To confirm that the effect of 11,12-EET on mesenteric microvessels was mediated by activation of HO, we incubated the microvessels with 11,12-EET and measured CO release. As shown in Fig. 3, 11,12-EET caused a 30% increase in CO release from mesenteric microvessels. To ascertain whether 11,12-EET mediated the increase in HO activity, mesenteric microvessels were treated with 11,12-EET and CrMP. The addition of CrMP prevented the 11,12-EET-mediated increase in HO activity.


Figure 3
View larger version (18K):
[in this window]
[in a new window]
  		Fig. 3. Effect of 11,12-EET on HO activity in mesenteric microvessels. Microvessels were incubated for 60 min with either 11,12-EET (10 µM) or 11,12-EET (10 µM) + CrMP (15 µM). Carbon monoxide was measured by gas chromatography. Results are expressed as means ± SE of 3 experiments. *P < 0.05 vs. nontreated mesenteric microvessels.

 
Effect of CORM-3 on mesenteric microvessel tone. To ascertain whether mesenteric microvessels respond to exogenous CO, a CO-donor (CORM-3) was applied to vessels preconstricted with PE. When added to a buffer with normal pH, CORM-3 releases CO. The CO released by CORM-3 caused vasodilatation of mesenteric microvessels only when pretreated with CrMP (Fig. 4).


Figure 4
View larger version (9K):
[in this window]
[in a new window]
  		Fig. 4. Dose-response effects of CORM-3 on mesenteric arterial microvessels preconstricted with PE before and after inhibition of HO with CrMP (15 µM). Results (means ± SE) are expressed as percent decrease in vasoconstriction produced by PE; n = 4. *P < 0.05.

 

   DISCUSSION
TOP
 ABSTRACT
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
GRANTS
 REFERENCES
 
Because 11,12-EET shares many of the effects that derive from activation of HO, the possibility that some actions of 11,12-EET are mediated by an HO-dependent mechanism has been examined in the present study and has been answered in the positive for rat mesenteric arterial vessels. Indeed, our results suggest that a key mechanism of action of 11,12-EET on rat mesenteric arteries is driven by stimulation of HO activity. This novel observation was substantiated by enzymatic activity, indicating that 11,12-EET increased HO activity as measured by increased CO production that was abolished by inhibition of HO with CrMP (Fig. 3). That a product of HO activity mediates the vasodilator action of 11,12-EET in the mesenteric microcirculation is supported by our results showing that vasodilation to 11,12-EET was independent of COX and was unaffected by inhibition of cGMP formation but was abolished by inhibition of HO with CrMP and of KCa channels with iberiotoxin. These findings are in agreement with those of Naik et al. (18) who demonstrated that CO, a product of HO, dilated the mesenteric circulation. Previous findings that depolarization of vascular smooth muscle (VSM) cells with a high-K+ media and blockade of KCa channels with iberiotoxin, charybdotoxin, or tetraethylammonium prevented the vasodilator response to EETs provide strong support for a primary role of K+ channels in mediating the vasodilator response to EETs (5, 8). Several investigators found that EETs have no effect on the activity of the KCa channel in inside-out detached membrane patches excised from VSM cells (26), suggesting that EETs do not directly activate the KCa channel in VSM.

CO directly activates KCa channels in vascular smooth muscle cells by altering the apparent calcium dependence of KCa channel activation (10, 13, 18, 26). The mechanisms of action of endogenous vs. exogenous CO are different. Naik et al. (18) showed that the effect of exogenous CO is sensitive to ODQ and iberiotoxin, whereas the effect of endogenous CO is cGMP independent, via activation of large-conductance KCa channels. Thus the effects of 11,12-EET and CO share similarities; our study suggests that the most important mechanism of action of 11,12-EET on the mesenteric microcirculation is through stimulation of endogenous CO production acting on KCa channels. Because vasodilatation to 11,12-EET was not inhibited by ODQ, whereas the effect of ACh was partially inhibited by ODQ, we can also exclude an effect of 11,12-EET through nitric oxide.

In response to 11,12-EET, the rabbit renal vasculature dilated independently of cyclooxygenase (6), as did the rat renal arcuate, interlobular, and afferent arterioles (7). 5,6-EET also dilated the rat renal arcuate artery (7) and the rabbit renal vasculature (6); however, in contrast to 11,12-EET, it exhibited a cyclooxygenase dependency. In our mesenteric microvessels, 5,6-EET caused vasodilatation that could not be blocked by inhibition of HO with CrMP. Additionally, the dilator response of the renal afferent arteriole to the sulfonimide analog of 11,12-EET was unaffected by guanylyl cyclase inhibition (11), as was the case for dilation of superior mesenteric arterial vessels in the present study (Fig. 1C). The vascular responses to both 11,12-EET and CO were inhibited by blockade of KCa channels (20, 26). Dependency of the vascular action on HO activity was evident for 8,9-EET (Fig. 2B) and accounted partially for the mesenteric vasodilator effect of 14,15-EET (Fig. 2C) but not for 5,6-EET (Fig. 2A). Thus the mechanism of the vascular action for each EET demonstrated a degree of specificity. However, species differences, experimental conditions (in vivo vs. in vitro), vascular territories (coronary vs. renal), and different blood vessel sizes (conduit arteries vs. arterioles) are factors that urge caution when interpreting differences noted on comparing studies of vascular responses to eicosanoids.

In conclusion, our results suggest a close interaction involving 11,12-EET and the HO/CO system in rat mesenteric arteries; namely, rat mesenteric vasodilation produced by 11,12-EET is related to activation of the HO system.


   GRANTS
TOP
 ABSTRACT
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 GRANTS
REFERENCES
 
This work was supported by National Heart, Lung, and Blood Institute Grants HL-34300 and HL-25394, National Institute of Diabetes and Digestive and Kidney Diseases Grants DK-056601 and DK-068134, and a grant from the Italian Ministry for Instruction, University, and Research.


   FOOTNOTES
 

Address for reprint requests and other correspondence: D. Sacerdoti, Dept. of Clinical and Experimental Medicine, Univ. of Padova, Italy, Via Giustiniani 2, 35100 Padova, Italy (e-mail: david.sacerdoti{at}unipd.it)

The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.


   REFERENCES
TOP
 ABSTRACT
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 GRANTS
 REFERENCES
 

  1. Abraham NG, Quan S, Mieyal PA, Yang L, Burke-Wolin T, Mingone CJ, Goodman AI, Nasjletti A, and Wolin MS. Modulation of cGMP by human HO-1 retrovirus gene transfer in pulmonary microvessel endothelial cells. Am J Physiol Lung Cell Mol Physiol 283: L1117–L1124, 2002.[Abstract/Free Full Text]
  2. Araujo JA, Meng L, Tward AD, Hancock WW, Zhai Y, Lee A, Ishikawa K, Iyer S, Buelow R, Busuttil RW, Shih DM, Lusis AJ, and Kupiec-Weglinski JW. Systemic rather than local heme oxygenase-1 overexpression improves cardiac allograft outcomes in a new transgenic mouse. J Immunol 171: 1572–1580, 2003.[Abstract/Free Full Text]
  3. Archer SL, Gragasin FS, Wu X, Wang S, McMurtry S, Kim DH, Platonov M, Koshal A, Hashimoto K, Campbell WB, Falck JR, and Michelakis ED. Endothelium-derived hyperpolarizing factor in human internal mammary artery is 11,12-epoxyeicosatrienoic acid and causes relaxation by activating smooth muscle BK(Ca) channels. Circulation 107: 769–776, 2003.[Abstract/Free Full Text]
  4. Bolognesi M, Sacerdoti D, Di Pascoli M, Angeli P, Quarta S, Sticca A, Pontisso P, Merkel C, and Gatta A. Haeme oxygenase mediates hyporeactivity to phenylephrine in the mesenteric vessels of cirrhotic rats with ascites. Gut 54:1630–1636, 2005.[Abstract/Free Full Text]
  5. Campbell WB, Gebremedhin D, Pratt PF, and Harder DR. Identification of epoxyeicosatrienoic acids as endothelium-derived hyperpolarizing factors. Circ Res 78: 415–423, 1996.[Abstract/Free Full Text]
  6. Carroll MA, Garcia MP, Falck JR, and McGiff JC. Cyclooxygenase dependency of the renovascular actions of cytochrome P450-derived arachidonate metabolites. J Pharmacol Exp Ther 260: 104–109, 1992.[Abstract/Free Full Text]
  7. Cheng MK, Doumad AB, Jiang H, Falck JR, McGiff JC, and Carroll MA. Epoxyeicosatrienoic acids mediate adenosine-induced vasodilation in rat preglomerular microvessels (PGMV) via A2A receptors. Br J Pharmacol 141: 441–448, 2004.[CrossRef][Web of Science][Medline]
  8. Eckman DM, Hopkins N, McBride C, and Keef KD. Endothelium-dependent relaxation and hyperpolarization in guinea-pig coronary artery: role of epoxyeicosatrienoic acid. Br J Pharmacol 124:181–189, 1998.[CrossRef][Web of Science][Medline]
  9. Fisslthaler B, Popp R, Kiss L, Potente M, Harder DR, Fleming I, and Busse R. Cytochrome P450 2C is an EDHF synthase in coronary arteries. Nature 401: 493–497, 1999.[CrossRef][Medline]
  10. Gagov H, Kadinov B, Hristov K, Boev K, Itzev D, Bolton T, and Duridanova D. Role of constitutively expressed heme oxygenase-2 in the regulation of guinea pig coronary artery tone. Pflügers Arch 446: 412–421, 2003.[CrossRef][Web of Science][Medline]
  11. Imig JD, Inscho EW, Deichmann PC, Reddy KM, and Falck JR. Afferent arteriolar vasodilation to the sulfonimide analog of 11,12-epoxyeicosatrienoic acid involves protein kinase A. Hypertension 33: 408–413, 1999.[Abstract/Free Full Text]
  12. Imig JD, Navar LG, Roman RJ, Reddy KK, and Falck JR. Actions of epoxygenase metabolites on the preglomerular vasculature. J Am Soc Nephrol 7: 2364–2370, 1996.[Abstract]
  13. Komuro T, Borsody MK, Ono S, Marton LS, Weir BK, Zhang ZD, Paik E, and Macdonald RL. The vasorelaxation of cerebral arteries by carbon monoxide. Exp Biol Med 226:860–865, 2001.[Abstract/Free Full Text]
  14. Liu H, Mount DB, Nasjletti A, and Wang W. Carbon monoxide stimulates the apical 70-pS K+ channel of the rat thick ascending limb. J Clin Invest 103: 963–970, 1999.[Web of Science][Medline]
  15. Makita K, Takahashi K, Karara A, Jacobson HR, Falck JR, and Capdevila JH. Experimental and/or genetically controlled alterations of the renal microsomal cytochrome P450 epoxygenase induce hypertension in rats fed a high salt diet. J Clin Invest 94: 2414–2420, 1994.[Web of Science][Medline]
  16. Michaelis UR, Fisslthaler B, Medhora M, Harder D, Fleming I, and Busse R. Cytochrome P450 2C9-derived epoxyeicosatrienoic acids induce angiogenesis via cross-talk with the epidermal growth factor receptor (EGFR). FASEB J 17: 770–772, 2003.[Abstract/Free Full Text]
  17. Miller AW, Dimitropoulou C, Han G, White RE, Busija DW, and Carrier GO. Epoxyeicosatrienoic acid-induced relaxation is impaired in insulin resistance. Am J Physiol Heart Circ Physiol 281: H1524–H1531, 2001.[Abstract/Free Full Text]
  18. Naik JS, O'Donaughy TL, and Walker BR. Endogenous carbon monoxide is an endothelial-derived vasodilator factor in the mesenteric circulation. Am J Physiol Heart Circ Physiol 284: H838–H845, 2003.[Abstract/Free Full Text]
  19. Node K, Huo Y, Ruan X, Yang B, Spiecker M, Ley K, Zeldin DC, and Liao JK. Anti-inflammatory properties of cytochrome P450 epoxygenase-derived eicosanoids. Science 285: 1276–1279, 1999.[Abstract/Free Full Text]
  20. Oltman CL, Weintraub NL, VanRollins M, and Dellsperger KC. Epoxyeicosatrienoic acids and dihydroxyeicosatrienoic acids are potent vasodilators in the canine coronary microcirculation. Circ Res 83: 932–939, 1998.[Abstract/Free Full Text]
  21. Rosolowsky M and Campbell WB. Synthesis of hydroxyeicosatetraenoic (HETEs) and epoxyeicosatrienoic acids (EETs) by cultured bovine coronary artery endothelial cells. Biochim Biophys Acta 1299: 267–277, 1996.[Medline]
  22. Sabaawy HE, Zhang F, Nguyen X, Elhosseiny A, Nasjletti A, Schwartzman M, Dennery P, Kappas A, and Abraham NG. Human heme oxygenase-1 gene transfer lowers blood pressure and promotes growth in spontaneously hypertensive rats. Hypertension 38: 210–215, 2001.[Abstract/Free Full Text]
  23. Spector AA, Fang X, Snyder GD, and Weintraub NL. Epoxyeicosatrienoic acids (EETs): metabolism and biochemical function. Prog Lipid Res 43: 55–90, 2004.[CrossRef][Web of Science][Medline]
  24. Wagener FA, da Silva JL, Farley T, de Witte T, Kappas A, and Abraham NG. Differential effects of heme oxygenase isoforms on heme mediation of endothelial intracellular adhesion molecule 1 expression. J Pharmacol Exp Ther 291: 416–423, 1999.[Abstract/Free Full Text]
  25. Wagner M, Cadetg P, Ruf R, Mazzucchelli L, Ferrari P, and Redaelli CA. Heme oxygenase-1 attenuates ischemia/reperfusion-induced apoptosis and improves survival in rat renal allografts. Kidney Int 63: 1564–1573, 2003.[CrossRef][Web of Science][Medline]
  26. Wang R, Wang Z, and Wu L. Carbon monoxide-induced vasorelaxation and the underlying mechanisms. Br J Pharmacol 121: 927–934, 1997.[CrossRef][Web of Science][Medline]
  27. Wei Y, Lin DH, Kemp R, Yaddanapudi GS, Nasjletti A, Falck JR, and Wang WH. Arachidonic acid inhibits epithelial Na channel via cytochrome P450 (CYP) epoxygenase-dependent metabolic pathways. J Gen Physiol 124: 719–727, 2004.[Abstract/Free Full Text]
  28. Wu S, Chen W, Murphy E, Gabel S, Tomer KB, Foley J, Steenbergen C, Falck JR, Moomaw CR, and Zeldin DC. Molecular cloning, expression, and functional significance of a cytochrome P450 highly expressed in rat heart myocytes. J Biol Chem 272: 12551–12559, 1997.[Abstract/Free Full Text]
  29. Zeldin DC. Epoxygenase pathways of arachidonic acid metabolism. J Biol Chem 276: 36059–36062, 2001.[Free Full Text]
  30. Zhang F, Kaide JI, Rodriguez-Mulero F, Abraham NG, and Nasjletti A. Vasoregulatory function of the heme-heme oxygenase-carbon monoxide system. Am J Hypertens 14: 62S–67S, 2001.[CrossRef][Web of Science][Medline]
  31. Zou AP, Fleming JT, Falck JR, Jacobs ER, Gebremedhin D, Harder DR, and Roman RJ. Stereospecific effects of epoxyeicosatrienoic acids on renal vascular tone and K+-channel activity. Am J Physiol Renal Fluid Electrolyte Physiol 270: F822–F832, 1996.[Abstract/Free Full Text]



This article has been cited by other articles:


Home page
 Am. J. Physiol. Renal Physiol.Home page
N. G. Abraham, J. Cao, D. Sacerdoti, X. Li, and G. Drummond
Heme oxygenase: the key to renal function regulation
Am J Physiol Renal Physiol, November 1, 2009; 297(5): F1137 - F1152.
[Abstract] [Full Text] [PDF]

Home page
 HypertensionHome page
D. E. Stec, H. A. Drummond, and T. Vera
Role of Carbon Monoxide in Blood Pressure Regulation
Hypertension, March 1, 2008; 51(3): 597 - 604.
[Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
291/4/H1999    most recent
00082.2006v2
00082.2006v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Web of Science (3)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Sacerdoti, D.
Right arrow Articles by Abraham, N. G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Sacerdoti, D.
Right arrow Articles by Abraham, N. G.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online
Copyright © 2006 by the American Physiological Society.