Login to MyKarger

New to MyKarger? Click here to sign up.



Login with Facebook

Forgot your password?

Authors, Editors, Reviewers

For Manuscript Submission, Check or Review Login please go to Submission Websites List.

Submission Websites List

Institutional Login
(Shibboleth or Open Athens)

For the academic login, please select your country in the dropdown list. You will be redirected to verify your credentials.

Research Paper

Calcium-Dependent Phospholipase A2 Mediates the Production of Endothelium-Derived Hyperpolarizing Factor in Perfused Rat Mesenteric Prearteriolar Bed

Adeagbo A.S.O. · Henzel M.K.

Author affiliations

Department of Physiology and Biophysics, and Center for Applied Microcirculatory Research, School of Medicine, University of Louisville, Louisville, Ky., USA

Related Articles for ""

J Vasc Res 1998;35:27–35

Do you have an account?

Login Information





Contact Information










I have read the Karger Terms and Conditions and agree.



Login Information





Contact Information










I have read the Karger Terms and Conditions and agree.



To view the fulltext, please log in

To view the pdf, please log in

Buy

  • FullText & PDF
  • Unlimited re-access via MyKarger
  • Unrestricted printing, no saving restrictions for personal use
read more

CHF 38.00 *
EUR 35.00 *
USD 39.00 *

Select

KAB

Buy a Karger Article Bundle (KAB) and profit from a discount!

If you would like to redeem your KAB credit, please log in.


Save over 20% compared to the individual article price.
Learn more

Rent/Cloud

  • Rent for 48h to view
  • Buy Cloud Access for unlimited viewing via different devices
  • Synchronizing in the ReadCube Cloud
  • Printing and saving restrictions apply

Rental: USD 8.50
Cloud: USD 20.00


Select

Subscribe

  • Access to all articles of the subscribed year(s) guaranteed for 5 years
  • Unlimited re-access via Subscriber Login or MyKarger
  • Unrestricted printing, no saving restrictions for personal use
read more

Subcription rates


Select

* The final prices may differ from the prices shown due to specifics of VAT rules.

Article / Publication Details

First-Page Preview
Abstract of Research Paper

Published online: February 06, 1998
Issue release date: January – February

Number of Print Pages: 9
Number of Figures: 5
Number of Tables: 1

ISSN: 1018-1172 (Print)
eISSN: 1423-0135 (Online)

For additional information: https://www.karger.com/JVR

Abstract

The isolated, perfused rat mesenteric bed releases a cytochrome P450-linked metabolite of arachidonic acid (AA) as endothelium-derived hyperpolarizing factor (EDHF) in response to acetylcholine and histamine. This study assessed the relative contribution of two AA-generating pathways, phospholipase A2 (PLA2) and diacylglycerol (DAG) lipase, to EDHF-mediated dilation of the rat mesenteric bed. We tested the hypothesis that PLA2-mediated release of AA is essential for the production of EDHF. Mesenteric beds were perfused with physiological salt solution (PSS) containing indomethacin and nitro-L-arginine methyl ester to block cyclooxygenase and nitric oxide synthase, respectively, and constricted with cirazoline (an α1-adrenoceptor agonist). Bolus applications of acetylcholine and histamine caused dose-dependent dilation of the constricted beds. The 85-kDa PLA2 inhibitor, arachidonyl trifluoromethyl ketone (AACOCF3), at 3 µM, profoundly blunted decreases in perfusion pressure initiated by 1 nmol acetylcholine (94.3 ± 1.7%) and by 100 nmol histamine (88.5 ± 3.3%) to 9.6 ± 7.5 and 8.6 ± 6.0%, respectively. AACOCF3 also blocked cirazoline-stimulated release of 6-keto-PG, but did not alter the vasodilation initiated by sodium nitroprusside (a nitric oxide donor), cromakalim (a K+ channel activator), or by Na+/K+-ATPase activation, as measured by KCl vasodilation in preconstricted beds perfused with K+-free PSS. The 14-kDa PLA2 inhibitor, oleyloxyethyl phosphorylcholine, also blocked EDHF vasodilation and also significantly inhibited K+ channel activity. Neither the Ca2+-independent PLA2 inhibitor, HELSS [E-6-(bromomethylene)-tetrahydro-3-(1-naphthalenyl)-2H-pyran-2-one], nor DAG lipase inhibitor, RHC-80267 [1,6-bis-(cyclohexyloximino-carbonylamino)-hexane] altered EDHF-mediated vasodilation. However, RHC-80267 blocked cirazoline-stimulated release of 6-keto-PGF. We conclude that Ca2+-dependent PLA2, rather than DAG lipase, generates the AA for the production of EDHF in the perfused rat mesenteric bed.


References

  1. Knowles RG, Moncada S: Nitric oxide synthases in mammals. Biochem J 1994;298:249–258.
    External Resources
  2. Moncada S, Palmer RMJ, Higgs EA: Nitric oxide: Physiology, pathophysiology and pharmacology. Pharmacol Rev 1991;43:109–142.
  3. Adeagbo ASO, Triggle CR: Varying [K+]ext reveals two components to acetylcholine (Ach)- and histamine (H)-induced vasodilatation in the perfused rat mesenteric arterial bed (MAB). Br J Pharmacol 1992;106:21P.
  4. Adeagbo ASO, Triggle CR: Varying extracellular [K+]: A functional approach to separating EDHF- and EDNO-related mechanisms in perfused rat mesenteric arterial bed. J Cardiovasc Pharmacol 1993;21:423–429.
  5. Bauersachs J, Hecker M, Busse R: Display of the characteristics of endothelium-derived hyperpolarizing factor by a cytochrome P450-derived arachidonic acid metabolite in the coronary microcirculation. Br J Pharmacol 1994;113:1548–1553.
  6. Hecker M, Bara AT, Bauersachs J, Busse R: Characterization of endothelium-derived hyperpolarizing factor as a cytochrome P450-derived arachidonic acid metabolite in mammals. J Physiol 1994;481:407–414.
  7. Campbell WB, Gebremedhin D, Pratt PF, Harder DR: Identification of epoxyeicosatrienoic acids as endothelium-derived hyperpolarizing factors. Circ Res 1996;78:415–423.
  8. Bell RL, Kennerly DA, Stanford N, Majerus PW: Diacylglyceride lipase: A pathway for arachidonic acid release from human platelets. Proc Natl Acad Sci 1979;76:3238–3241.
  9. Sutherland CA, Amin D: Relative activities of rat and dog platelet phospholipase A2 and diglyceride lipase: Selective inhibition of diglyceride lipase by RHC-80267. J Biol Chem 1982;257:14006–14010.
    External Resources
  10. Riendeau D, Guay J, Weech PK, et al: Arachidonyl trifluoromethyl ketone, a potent inhibitor of 85-kDa phospholipase A2, blocks production of arachidonate and 12-hydroxyeicosatetraenoic acid by calcium ionophore-challenged platelets. J Biol Chem 1994;269:15619–15624.
  11. Clark JD, Lin L-L, Kriz RW, et al: A novel arachidonic acid-selective cytosolic PLA2 contains a Ca2+-dependent translocation domain with homology to PKC and GAP. Cell 1991;65:1043–1051.
  12. Kramer RM, Roberts EF, Manetta JV, et al: Ca2+-sensitive cytosolic phospholipase A2 (cPLA2) in human platelets. J Lipid Mediat 1993;6:209–216.
    External Resources
  13. Hanel AM, Schuttel S, Gelb MH: Processive interfacial catalysis by mammalian 85-kilodalton phospholipase A2 enzymes on product-containing vesicles: Application to the determination of substrate preferences. Biochemistry 1993;32:5949–5958.
    External Resources
  14. Street IP, Lin H-K, Laliberte F, et al: Slow- and tight-binding inhibitors of the 85-kDa human phospholipase A2. Biochemistry 1993;32:5935–5940.
    External Resources
  15. Bartoli F, Lin K-K, Ghomashchi F, et al: Tight binding inhibitors of 85-kDa phospholipase A2 but not 14-kDa phospholipase A2 inhibit release of free arachidonate in thrombin-stimulated human platelets. J Biol Chem 1994;269:15619–15630.
  16. Hope WC, Chen T, Morgan DW: Secretory phospholipase A2 inhibitors and calmodulin antagonists as inhibitors of cytosolic phospholipase A2. Agents Actions 1993;39:C39–C42.
    External Resources
  17. Hazen SL, Zupan LA, Weiss RH, et al: Suicide inhibition of canine myocardial cytosolic calcium-independent phospholipase A2: Mechanism-based discrimination between calcium-dependent and -independent phospholipase A2. J Biol Chem 1991;266:7227–7232.
  18. Lehman JJ, Brown KA, Ramanadham S, et al: Arachidonic acid release from aortic smooth muscle cells induced by [Arg8]vasopressin is largely mediated by calcium-independent phospholipase A2. J Biol Chem 1993;268:20713–20716.
  19. Ackermann EJ, Conde-Frieboes K, Dennis EA: Inhibition of macrophage Ca2+-independent phospholipase A2 by bromoenol lactone and trifluoromethyl ketones. J Biol Chem 1995;270:445–450.
  20. Adeagbo ASO: Nitro-L-arginine methyl ester (L-NAME) insensitive vasodilation of perfused rat mesenteric bed is mediated by an arachidonic acid (AA) metabolite (abstract 57). FASEB J 1996;10/3:A10.
  21. McGregor DD: The effect of sympathetic nerve stimulation on vasoconstrictor responses in perfused mesenteric blood vessels of the rat. J Physiol 1965;177:21–30.
  22. Fulton D, McGiff JC, Quilley J: Role of phospholipase C and phospholipase A2 in the nitric oxide-independent vasodilator effect of bradykinin in the rat perfused heart. J Pharmacol Exp Ther 1996;278:518–526.
  23. Wolfe LS, Rostworowski K, Manku M: Measurement of prostaglandin synthesis and release from rat aortic tissue and from the perfused mesenteric artery by gas chromatography-mass spectrometric methods; in Vane JR, Bergstrom S (eds): Prostacyclin. New York, Raven Press, 1979, pp 113–118.
  24. Taylor SG, Weston AH. Endothelium-derived hyperpolarizing factor: An endogenous inhibitor from the vascular endothelium. Trends Pharmacol Sci 1988;9:272–274.
  25. Komori K, Vanhoutte PM: Endothelium-derived relaxing factor. Blood Vessels 1990;27:238–245.
    External Resources
  26. Adeagbo ASO: Cytochrome P450 inhibitors modulates L-NAME-resistant vasodilation and vascular tone in perfused mesenteric bed. Am J Hypertens 1995;8/2:112A.
  27. Adeagbo ASO, Malik KU: Contribution of K+ channels to arachidonic acid-induced endothelium-dependent vasodilation in rat isolated perfused mesenteric arteries. J Pharmacol Exp Ther 1991;258:452–458.
    External Resources
  28. Hu S, Kim HS: Activation of K+ channel in vascular smooth muscles by cytochrome P450 metabolites of arachidonic acid. Eur J Pharmacol 1993;230:215–221.
  29. Oglesby TD, Gorman RR: The inhibition of arachidonic acid metabolism in human platelets by RHC 80267, a diacylglycerol lipase inhibitor. Biochim Biophys Acta 1984;793:269–277.
    External Resources
  30. Gronich JA, Bonventre JV, Nemenoff RA: Identification and characterization of a hormonally regulated form of phospholipase A2 in rat renal mesangial cells. J Biol Chem 1988;263:16645–16651.
  31. Nakazato Y, Simonson MS, Herman WH, et al: Interleukin-1α stimulates prostaglandin biosynthesis in serum-activated mesangial cells by induction of a non-pancreatic (type II) phospholipase A2. J Biol Chem 1991;266:14119–14127.
  32. Kramer RM, Hession C, Johansen B, et al: Structure and properties of a human nonpancreatic phospholipase A2. J Biol Chem 1989;264:5768–5775.
  33. Takayama K, Kudo I, Kim DK, et al: Purification and characterization of human platelet phospholipase A2 which preferentially hydrolyzes an arachidonyl residue. FEBS Lett 1991;282:326–338.
  34. Furchgott RF, Zawadzki JV: The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature 1980;288:373–376.
  35. Singer HA, Peach MJ: 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;226:796–801.
    External Resources
  36. Cook NS, Haylett DG: Effects of apamin, quinine and neuromuscular blockers on calcium-activated potassium channels in guinea-pig hepatocytes. J Physiol 1985;358:373–394.
    External Resources
  37. Johns RA, Peach MJ: Para-bromophenacyl bromide inhibits endothelium-dependent arterial relaxation and cyclic GMP accumulation by effects produced exclusively in the smooth muscle. J Pharmacol Exp Ther 1988;244:859–865.
    External Resources
  38. Chen G, Suzuki H: Endothelium-dependent hyperpolarization elicited by adenine compounds in rabbits carotid artery. Am J Physiol 1991;260:H1037–H1042.
    External Resources
  39. Nagao T, Illiano S, Vanhoutte PM: Calmodulin antagonists inhibit endothelium-dependent hyperpolarization in canine coronary artery. Br J Pharmacol 1992;107:382–386.
    External Resources
  40. Illiano S, Nagao T, Vanhoutte PM: Calmidazolium, a calmodulin inhibitor, inhibits endothelium-dependent relaxations resistant to nitro-L-arginine in the canine coronary artery. Br J Pharmacol 1992;107:387–392.
    External Resources

Article / Publication Details

First-Page Preview
Abstract of Research Paper

Published online: February 06, 1998
Issue release date: January – February

Number of Print Pages: 9
Number of Figures: 5
Number of Tables: 1

ISSN: 1018-1172 (Print)
eISSN: 1423-0135 (Online)

For additional information: https://www.karger.com/JVR


Copyright / Drug Dosage / Disclaimer

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.