Evidence Against the Involvement of Cytochrome P450 Metabolites in Endothelium-dependent Hyperpolarization of the Rat Main Mesenteric Artery

Overview

Journal J Physiol

Specialty Physiology

Date 1997 Jun 1

PMID 9192305

Citations 18

Authors

B VanHeel

J Van de Voorde

Affiliations

Soon will be listed here.

Abstract

1. The influence of different inhibitors of cytochrome P450 mono-oxygenase on the endothelium-dependent and -independent hyperpolarization in the isolated rat main mesenteric artery was investigated. 2. Application of acetylcholine (ACh; 1 microM) for 10 min evoked an endothelium-dependent peak hyperpolarization of about 18 mV followed by a partial recovery to a level 7 mV more negative than the resting value (-50.2 +/- 0.5 mV). 3. Proadifen (30 microM) completely and reversibly inhibited the ACh-induced hyperpolarization. Conversely, the imidazole antimycotics clotrimazole (30 microM) and miconazole (100 microM) had less effect on the peak endothelium-dependent hyperpolarization. The suicide substrate inhibitors 17-octadecynoic acid (17-ODYA; 5 microM) and 1-aminobenzotriazole (1-ABT; 2 mM) did not significantly influence endothelium-dependent hyperpolarization. 4. The endothelium-independent hyperpolarization (16 mV) evoked by leveromakalim (300 nM) was completely inhibited by proadifen as well as by clotrimazole and miconazole but was not affected by 17-ODYA or 1-ABT. 5. These results do not support the view that the ACh-induced endothelium-dependent hyperpolarization in the rat mesenteric artery is mediated by cytochrome P450 mono-oxygenase metabolites. Proadifen and imidazole antimycotics impair the activation of ATP-regulated K+ channels in mesenteric artery cells, rendering non-specific inhibition of smooth muscle K+ channel activation an alternative explanation for the inhibitory influence of some (but not all) P450 inhibitors on endothelium-dependent hyperpolarization in this preparation.

Citing Articles

Cyp2c44 epoxygenase-derived epoxyeicosatrienoic acids in vascular smooth muscle cells elicit vasoconstriction of the murine ophthalmic artery.

Hu J, Sisignano M, Brecht R, Perumal N, Angioni C, Bibli I Sci Rep. 2021; 11(1):18764.

PMID: 34548575 PMC: 8455677. DOI: 10.1038/s41598-021-98236-w.

1-Aminobenzotriazole: A Mechanism-Based Cytochrome P450 Inhibitor and Probe of Cytochrome P450 Biology.

de Montellano P Med Chem (Los Angeles). 2018; 8(3).

PMID: 30221034 PMC: 6137267. DOI: 10.4172/2161-0444.1000495.

Connexins and gap junctions in the EDHF phenomenon and conducted vasomotor responses.

De Wit C, Griffith T Pflugers Arch. 2010; 459(6):897-914.

PMID: 20379740 DOI: 10.1007/s00424-010-0830-4.

Enalapril treatment alters the contribution of epoxyeicosatrienoic acids but not gap junctions to endothelium-derived hyperpolarizing factor activity in mesenteric arteries of spontaneously hypertensive rats.

Ellis A, Goto K, Chaston D, Brackenbury T, Meaney K, Falck J J Pharmacol Exp Ther. 2009; 330(2):413-22.

PMID: 19411610 PMC: 2713080. DOI: 10.1124/jpet.109.152116.

Cytochrome P450 oxidoreductase participates in nitric oxide consumption by rat brain.

Hall C, Keynes R, Garthwaite J Biochem J. 2009; 419(2):411-8.

PMID: 19152507 PMC: 2662488. DOI: 10.1042/BJ20082419.

References

Volpi M, Shaafi R, Epstein P, Andrenyak D, Feinstein M . Local anesthetics, mepacrine, and propranolol are antagonists of calmodulin. Proc Natl Acad Sci U S A. 1981; 78(2):795-9. PMC: 319889. DOI: 10.1073/pnas.78.2.795. View

Murphy M, Brayden J . Nitric oxide hyperpolarizes rabbit mesenteric arteries via ATP-sensitive potassium channels. J Physiol. 1995; 486 ( Pt 1):47-58. PMC: 1156495. DOI: 10.1113/jphysiol.1995.sp020789. View

Singer H, Peach M . Endothelium-dependent relaxation of rabbit aorta. II. Inhibition of relaxation stimulated by methacholine and A23187 with antagonists of arachidonic acid metabolism. J Pharmacol Exp Ther. 1983; 226(3):796-801. View

Ignarro L, Kadowitz P . The pharmacological and physiological role of cyclic GMP in vascular smooth muscle relaxation. Annu Rev Pharmacol Toxicol. 1985; 25:171-91. DOI: 10.1146/annurev.pa.25.040185.001131. View

Feletou M, Vanhoutte P . Endothelium-dependent hyperpolarization of canine coronary smooth muscle. Br J Pharmacol. 1988; 93(3):515-24. PMC: 1853853. DOI: 10.1111/j.1476-5381.1988.tb10306.x. View

Chen G, Suzuki H, Weston A . Acetylcholine releases endothelium-derived hyperpolarizing factor and EDRF from rat blood vessels. Br J Pharmacol. 1988; 95(4):1165-74. PMC: 1854275. DOI: 10.1111/j.1476-5381.1988.tb11752.x. View

Taylor S, Weston A . Endothelium-derived hyperpolarizing factor: a new endogenous inhibitor from the vascular endothelium. Trends Pharmacol Sci. 1988; 9(8):272-4. DOI: 10.1016/0165-6147(88)90003-x. View

FURCHGOTT R, Vanhoutte P . Endothelium-derived relaxing and contracting factors. FASEB J. 1989; 3(9):2007-18. View

Chen G, Suzuki H . Some electrical properties of the endothelium-dependent hyperpolarization recorded from rat arterial smooth muscle cells. J Physiol. 1989; 410:91-106. PMC: 1190468. DOI: 10.1113/jphysiol.1989.sp017522. View

10.

Rosolowsky M, Falck J, Willerson J, Campbell W . Synthesis of lipoxygenase and epoxygenase products of arachidonic acid by normal and stenosed canine coronary arteries. Circ Res. 1990; 66(3):608-21. DOI: 10.1161/01.res.66.3.608. View

11.

Tare M, Parkington H, Coleman H, Neild T, Dusting G . Hyperpolarization and relaxation of arterial smooth muscle caused by nitric oxide derived from the endothelium. Nature. 1990; 346(6279):69-71. DOI: 10.1038/346069a0. View

12.

Rees D, Palmer R, Schulz R, HODSON H, Moncada S . Characterization of three inhibitors of endothelial nitric oxide synthase in vitro and in vivo. Br J Pharmacol. 1990; 101(3):746-52. PMC: 1917753. DOI: 10.1111/j.1476-5381.1990.tb14151.x. View

13.

McPherson G, Angus J . Evidence that acetylcholine-mediated hyperpolarization of the rat small mesenteric artery does not involve the K+ channel opened by cromakalim. Br J Pharmacol. 1991; 103(1):1184-90. PMC: 1908110. DOI: 10.1111/j.1476-5381.1991.tb12321.x. View

14.

Fukao M, Hattori Y, Kanno M, Sakuma I, Kitabatake A . Thapsigargin- and cyclopiazonic acid-induced endothelium-dependent hyperpolarization in rat mesenteric artery. Br J Pharmacol. 1995; 115(6):987-92. PMC: 1909013. DOI: 10.1111/j.1476-5381.1995.tb15908.x. View

15.

Campbell W, Gebremedhin D, Pratt P, Harder D . Identification of epoxyeicosatrienoic acids as endothelium-derived hyperpolarizing factors. Circ Res. 1996; 78(3):415-23. DOI: 10.1161/01.res.78.3.415. View

16.

Corriu C, Feletou M, Canet E, Vanhoutte P . Inhibitors of the cytochrome P450-mono-oxygenase and endothelium-dependent hyperpolarizations in the guinea-pig isolated carotid artery. Br J Pharmacol. 1996; 117(4):607-10. PMC: 1909333. DOI: 10.1111/j.1476-5381.1996.tb15233.x. View

17.

Zygmunt P, Hogestatt E . Role of potassium channels in endothelium-dependent relaxation resistant to nitroarginine in the rat hepatic artery. Br J Pharmacol. 1996; 117(7):1600-6. PMC: 1909442. DOI: 10.1111/j.1476-5381.1996.tb15327.x. View

18.

Zygmunt P, Edwards G, Weston A, Davis S, Hogestatt E . Effects of cytochrome P450 inhibitors on EDHF-mediated relaxation in the rat hepatic artery. Br J Pharmacol. 1996; 118(5):1147-52. PMC: 1909609. DOI: 10.1111/j.1476-5381.1996.tb15517.x. View

19.

Edwards G, Zygmunt P, Hogestatt E, Weston A . Effects of cytochrome P450 inhibitors on potassium currents and mechanical activity in rat portal vein. Br J Pharmacol. 1996; 119(4):691-701. PMC: 1915770. DOI: 10.1111/j.1476-5381.1996.tb15728.x. View

20.

Van de Voorde J, VanHeel B, LEUSEN I . Endothelium-dependent relaxation and hyperpolarization in aorta from control and renal hypertensive rats. Circ Res. 1992; 70(1):1-8. DOI: 10.1161/01.res.70.1.1. View