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. 1993 Apr;91(4):1374–1379. doi: 10.1172/JCI116339

Vasodilator and constrictor actions of platelet-activating factor in the isolated microperfused afferent arteriole of the rabbit kidney. Role of endothelium-derived relaxing factor/nitric oxide and cyclooxygenase products.

L A Juncos 1, Y L Ren 1, S Arima 1, S Ito 1
PMCID: PMC288109  PMID: 8473488

Abstract

It has been suggested that platelet-activating factor (PAF) plays a prominent role in the control of glomerular hemodynamics in various physiological and pathological conditions. We examined the direct effect of PAF on rabbit glomerular afferent arterioles (Af-Arts) microperfused in vitro and tested whether endothelium-derived relaxing factor/nitric oxide (EDNO) and cyclooxygenase products are involved in its actions. In nanomolar concentrations PAF caused dose-dependent constriction of Af-Arts, with the maximum constriction being 34 +/- 10% at 4 x 10(-8) M (n = 9, P < 0.001). The constriction was blunted by cyclooxygenase inhibition (11 +/- 6%, n = 7, P < 0.05) but augmented by EDNO inhibition (76 +/- 14%, n = 8, P < 0.005). To study a possible vasodilator effect of PAF, Af-Arts were preconstricted with norepinephrine and increasing concentrations of PAF added to the lumen. At picomolar concentrations (lower than those that caused constriction), PAF produced dose-dependent vasodilation that was unaffected by cyclooxygenase inhibition but was abolished by EDNO synthesis inhibition. Both PAF-induced constriction and dilation of Af-Arts were blocked by a PAF receptor antagonist. This study demonstrates that PAF has a receptor-mediated biphasic effect on rabbit Af-Arts, dilating them at low concentrations while constricting them at higher concentrations. Our results suggest that PAF's vasodilator action may be due to production of EDNO, while its constrictor action is mediated at least in part through cyclooxygenase products.

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Selected References

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  1. Alving K., Matran R., Lundberg J. M. The possible role of prostaglandin D2 in the long-lasting airways vasodilatation induced by allergen in the sensitized pig. Acta Physiol Scand. 1991 Sep;143(1):93–103. doi: 10.1111/j.1748-1716.1991.tb09204.x. [DOI] [PubMed] [Google Scholar]
  2. Badr K. F., DeBoer D. K., Takahashi K., Harris R. C., Fogo A., Jacobson H. R. Glomerular responses to platelet-activating factor in the rat: role of thromboxane A2. Am J Physiol. 1989 Jan;256(1 Pt 2):F35–F43. doi: 10.1152/ajprenal.1989.256.1.F35. [DOI] [PubMed] [Google Scholar]
  3. Bertani T., Livio M., Macconi D., Morigi M., Bisogno G., Patrono C., Remuzzi G. Platelet activating factor (PAF) as a mediator of injury in nephrotoxic nephritis. Kidney Int. 1987 Jun;31(6):1248–1256. doi: 10.1038/ki.1987.138. [DOI] [PubMed] [Google Scholar]
  4. Braquet P., Touqui L., Shen T. Y., Vargaftig B. B. Perspectives in platelet-activating factor research. Pharmacol Rev. 1987 Jun;39(2):97–145. [PubMed] [Google Scholar]
  5. Bussolino F., Aglietta M., Sanavio F., Stacchini A., Lauri D., Camussi G. Alkyl-ether phosphoglycerides influence calcium fluxes into human endothelial cells. J Immunol. 1985 Oct;135(4):2748–2753. [PubMed] [Google Scholar]
  6. Camussi G. Potential role of platelet-activating factor in renal pathophysiology. Kidney Int. 1986 Feb;29(2):469–477. doi: 10.1038/ki.1986.23. [DOI] [PubMed] [Google Scholar]
  7. Caramelo C., Fernández-Gallardo S., Marín-Cao D., Iñarrea P., Santos J. C., López-Novoa J. M., Sanchez Crespo M. Presence of platelet-activating factor in blood from humans and experimental animals. Its absence in anephric individuals. Biochem Biophys Res Commun. 1984 May 16;120(3):789–796. doi: 10.1016/s0006-291x(84)80176-x. [DOI] [PubMed] [Google Scholar]
  8. Dillon P. K., Ritter A. B., Durán W. N. Vasoconstrictor effects of platelet-activating factor in the hamster cheek pouch microcirculation: dose-related relations and pathways of action. Circ Res. 1988 Apr;62(4):722–731. doi: 10.1161/01.res.62.4.722. [DOI] [PubMed] [Google Scholar]
  9. Edwards R. M. Response of isolated renal arterioles to acetylcholine, dopamine, and bradykinin. Am J Physiol. 1985 Feb;248(2 Pt 2):F183–F189. doi: 10.1152/ajprenal.1985.248.2.F183. [DOI] [PubMed] [Google Scholar]
  10. Felsen D., Loo M. H., Marion D. N., Vaughan E. D., Jr Involvement of platelet activating factor and thromboxane A2 in the renal response to unilateral ureteral obstruction. J Urol. 1990 Jul;144(1):141–145. doi: 10.1016/s0022-5347(17)39397-7. [DOI] [PubMed] [Google Scholar]
  11. Handa R. K., Strandhoy J. W., Buckalew V. M., Jr Platelet-activating factor is a renal vasodilator in the anesthetized rat. Am J Physiol. 1990 Jun;258(6 Pt 2):F1504–F1509. doi: 10.1152/ajprenal.1990.258.6.F1504. [DOI] [PubMed] [Google Scholar]
  12. Handa R. K., Strandhoy J. W., Buckalew V. M., Jr Vasorelaxant effect of C16-PAF and C18-PAF on renal blood flow and systemic blood pressure in the anesthetized rat. Life Sci. 1991;49(10):747–752. doi: 10.1016/0024-3205(91)90107-m. [DOI] [PubMed] [Google Scholar]
  13. Hwang S. B., Lee C. S., Cheah M. J., Shen T. Y. Specific receptor sites for 1-O-alkyl-2-O-acetyl-sn-glycero-3-phosphocholine (platelet activating factor) on rabbit platelet and guinea pig smooth muscle membranes. Biochemistry. 1983 Sep 27;22(20):4756–4763. doi: 10.1021/bi00289a022. [DOI] [PubMed] [Google Scholar]
  14. Ito S., Carretero O. A. An in vitro approach to the study of macula densa-mediated glomerular hemodynamics. Kidney Int. 1990 Dec;38(6):1206–1210. doi: 10.1038/ki.1990.335. [DOI] [PubMed] [Google Scholar]
  15. Ito S., Johnson C. S., Carretero O. A. Modulation of angiotensin II-induced vasoconstriction by endothelium-derived relaxing factor in the isolated microperfused rabbit afferent arteriole. J Clin Invest. 1991 May;87(5):1656–1663. doi: 10.1172/JCI115181. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Ito S., Juncos L. A., Nushiro N., Johnson C. S., Carretero O. A. Endothelium-derived relaxing factor modulates endothelin action in afferent arterioles. Hypertension. 1991 Jun;17(6 Pt 2):1052–1056. doi: 10.1161/01.hyp.17.6.1052. [DOI] [PubMed] [Google Scholar]
  17. Itoh S., Carretero O. A., Murray R. D. Renin release from isolated afferent arterioles. Kidney Int. 1985 May;27(5):762–767. doi: 10.1038/ki.1985.77. [DOI] [PubMed] [Google Scholar]
  18. Kamata K., Mori T., Shigenobu K., Kasuya Y. Endothelium-dependent vasodilator effects of platelet activating factor on rat resistance vessels. Br J Pharmacol. 1989 Dec;98(4):1360–1364. doi: 10.1111/j.1476-5381.1989.tb12685.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Lee T. C., Malone B., Woodard D., Snyder F. Renal necrosis and the involvement of a single enzyme of the de novo pathway for the biosynthesis of platelet-activating factor in the rat kidney inner medulla. Biochem Biophys Res Commun. 1989 Sep 15;163(2):1002–1005. doi: 10.1016/0006-291x(89)92321-8. [DOI] [PubMed] [Google Scholar]
  20. Marsden P. A., Brock T. A., Ballermann B. J. Glomerular endothelial cells respond to calcium-mobilizing agonists with release of EDRF. Am J Physiol. 1990 May;258(5 Pt 2):F1295–F1303. doi: 10.1152/ajprenal.1990.258.5.F1295. [DOI] [PubMed] [Google Scholar]
  21. Masugi F., Ogihara T., Otsuka A., Saeki S., Kumahara Y. Effect of 1-alkyl-2-acetyl-sn-glycero-3-phosphorylcholine inhibitor on the reduction of one-kidney, one clip hypertension after unclipping in the rat. Life Sci. 1984 Jan 9;34(2):197–201. doi: 10.1016/0024-3205(84)90591-5. [DOI] [PubMed] [Google Scholar]
  22. Moncada S., Palmer R. M., Higgs E. A. Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacol Rev. 1991 Jun;43(2):109–142. [PubMed] [Google Scholar]
  23. Moore P. K., al-Swayeh O. A., Chong N. W., Evans R. A., Gibson A. L-NG-nitro arginine (L-NOARG), a novel, L-arginine-reversible inhibitor of endothelium-dependent vasodilatation in vitro. Br J Pharmacol. 1990 Feb;99(2):408–412. doi: 10.1111/j.1476-5381.1990.tb14717.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Osgood R. W., Patton M., Hanley M. J., Venkatachalam M., Reineck H. J., Stein J. H. In vitro perfusion of the isolated dog glomerulus. Am J Physiol. 1983 Mar;244(3):F349–F354. doi: 10.1152/ajprenal.1983.244.3.F349. [DOI] [PubMed] [Google Scholar]
  25. Remuzzi G. Eicosanoids and platelet activating factor as possible mediators of injury in experimental nephropathies. Adv Exp Med Biol. 1989;259:221–247. doi: 10.1007/978-1-4684-5700-1_10. [DOI] [PubMed] [Google Scholar]
  26. Rouis M., Nigon F., Chapman M. J. Platelet activating factor is a potent stimulant of the production of active oxygen species by human monocyte-derived macrophages. Biochem Biophys Res Commun. 1988 Nov 15;156(3):1293–1301. doi: 10.1016/s0006-291x(88)80773-3. [DOI] [PubMed] [Google Scholar]
  27. Scherf H., Nies A. S., Schwertschlag U., Hughes M., Gerber J. G. Hemodynamic effects of platelet activating factor in the dog kidney in vivo. Hypertension. 1986 Sep;8(9):737–741. doi: 10.1161/01.hyp.8.9.737. [DOI] [PubMed] [Google Scholar]
  28. Schwertschlag U. S., Whorton A. R. Platelet-activating factor-induced homologous and heterologous desensitization in cultured vascular smooth muscle cells. J Biol Chem. 1988 Sep 25;263(27):13791–13796. [PubMed] [Google Scholar]
  29. Schwertschlag U., Scherf H., Gerber J. G., Mathias M., Nies A. S. L-platelet activating factor induces changes on renal vascular resistance, vascular reactivity, and renin release in the isolated perfused rat kidney. Circ Res. 1987 Apr;60(4):534–539. doi: 10.1161/01.res.60.4.534. [DOI] [PubMed] [Google Scholar]
  30. Snyder F. Platelet-activating factor and related acetylated lipids as potent biologically active cellular mediators. Am J Physiol. 1990 Nov;259(5 Pt 1):C697–C708. doi: 10.1152/ajpcell.1990.259.5.C697. [DOI] [PubMed] [Google Scholar]
  31. Tokumura A., Homma H., Hanahan D. J. Structural analogs of alkylacetylglycerophosphocholine inhibitory behavior on platelet activation. J Biol Chem. 1985 Oct 15;260(23):12710–12714. [PubMed] [Google Scholar]
  32. Tolins J. P., Vercellotti G. M., Wilkowske M., Ha B., Jacob H. S., Raij L. Role of platelet activating factor in endotoxemic acute renal failure in the male rat. J Lab Clin Med. 1989 Mar;113(3):316–324. [PubMed] [Google Scholar]
  33. Vandongen R. Platelet activating factor and the circulation. J Hypertens. 1991 Sep;9(9):771–778. doi: 10.1097/00004872-199109000-00001. [DOI] [PubMed] [Google Scholar]
  34. Wang J., Dunn M. J. Platelet-activating factor mediates endotoxin-induced acute renal insufficiency in rats. Am J Physiol. 1987 Dec;253(6 Pt 2):F1283–F1289. doi: 10.1152/ajprenal.1987.253.6.F1283. [DOI] [PubMed] [Google Scholar]
  35. Yoo J., Schlondorff D., Neugarten J. Thromboxane mediates the renal hemodynamic effects of platelet activating factor. J Pharmacol Exp Ther. 1990 May;253(2):743–748. [PubMed] [Google Scholar]

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