Skip to main content
Log in

The role of prostaglandins in the endothelium-mediated vasodilatory response to hypoxia

  • Heart, Circulation, Respiration and Blood; Environmental and Exercise Physiology
  • Published:
Pflügers Archiv Aims and scope Submit manuscript

Abstract

The effect of intraluminal hypoxia on vascular tone and the release of prostaglandins (PG) I2 and E2 were investigated in intact isolated segments of canine femoral and coronary arteries as well as in the rat tail artery. Perfusion with hypoxic Tyrode's solution (pO2∶ 20–40 mm Hg) evoked a marked vasodilation of the segments, precontracted with norepinephrine or serotonin. Simultaneously, a 2–3-fold increase in the release of 6-keto-PGF (the stable hydrolysis product of PGI2) could be observed. In parallel to 6-keto-PGF, smaller quantities of PGE2 were released. Removal of the endothelium as well as pretreatment with indomethacin abolished both, the dilatory response and the PG-release. After administration of verapamil as well as 3,4,5-trimethoxybenzoic acid 8-diethyl-aminooctylester (TMB-8) (which binds intracellular calcium) the PG-increase was abolished and hypoxic dilatation could no longer be elicited, although the vessel had still a capacity to dilate. Exogenous administration of PGI2 and PGE2 showed that in canine femoral and coronary arteries PGI2 was the most effective vasodilating prostaglandin, while in the rat tail artery PGE2 had a 10-fold higher dilating potency compared to PGI2. At very high concentrations both PGI2 and PGE2 caused vasoconstriction. Our experiments suggest that the hypoxic endothelium-dependent dilatation may be mediated by an increased PG-release. Hypoxia-induced transmembrane calcium influx into the endothelial cells seems to be the trigger reaction.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Altura BM, Chand N (1981) Bradykinin-induced relaxation of renal and pulmonary arteries is dependent upon intact endothelial cells. Br J Pharmacol 74:10–11

    Google Scholar 

  • Beetens JR, van Hove C, Rampart M, Herman AG (1983) Acetylcholine stimulates the release of prostacyclin by rabbit aorta endothelium. J Pharm Pharmacol 35:251–252

    Google Scholar 

  • Billah MM, Lapetina EG (1982) Evidence for multiple metabolic pools of phosphatidylinositol in stimulated platelets. J Biol Chem 257:11856–11859

    Google Scholar 

  • Block AJ, Feinberg H, Herbaczynska-Cedro K, Vane JR (1975) Anoxia-induced release of prostaglandins in rabbit isolated hearts. Circ Res 36:34–42

    Google Scholar 

  • Borda ES, Sterin-Borda L, Gimeno MF, Lazzari MA, Gimeno AL (1983) The stimulatory effect of prostacyclin (PGI2) on isolated rabbit and rat aorta is probably associated to the generation of a thromboxane A2 (TXA2) “like-material”. Arch Int Pharmacodyn 261:79–89

    Google Scholar 

  • Busse R, Pohl U, Kellner C, Klemm U (1983) Endothelial cells are involved in the vasodilatory response to hypoxia. Pflügers Arch 397:78–80

    Google Scholar 

  • Charo If, Feinman RD, Detwiler TC (1976) Inhibition of platelet secretion by an antagonist of intracellular calcium. Biophys Res Comm 72:1462–1467

    Google Scholar 

  • Coburn RF, Grubb B, Aronson RD (1979) Effect of cyanide on oxygen tension-dependent mechanical tension in rabbit aorta. Circ Res 14:368–378

    Google Scholar 

  • De Mey JG, Claeys M, Vanhoutte PM (1982) Endothelium-dependent inhibitory effects of acetylcholine, adenosine triphosphate, thrombin and arachidonic acid in the canine femoral artery J Pharmacol Exp Ther 222:166–173

    Google Scholar 

  • De Mey JG, Vanhoutte PM (1983) Anoxia and endothelium-dependent reactivity of the canine femoral artery. J Physiol 335:65–74

    Google Scholar 

  • Dusting GJ, Moncada S, Vane JR (1978) Vascular actions of arachidonic acid and its metabolites in perfused mesenteric and femoral beds of the dog. Eur J Pharmacol 49:65–72

    Google Scholar 

  • Edlund A, Fredholm BB, Patrignani P, Patrono C, Wennmalm A, Wennmalm M (1983) Release of two vasodilators, adenosine and prostacyclin, from isolated rabbit hearts during controlled hypoxia. J Physiol 340:487–501

    Google Scholar 

  • Ellis EF, Wei EP, Kontos HA (1979) Vasodilation of cat cerebral arterioles by prostaglandins D2, E2, G2, and I2. Am J Physiol 237:H381-H385

    Google Scholar 

  • Förstermann U, Hertting G, Neufang B (1984) The importance of endogenous prostaglandins other than prostacyclin for the modulation of contractility of some rabbit blood vessels. Br J Pharmacol 81:623–630

    Google Scholar 

  • Förstermann U, Neufang B (1984) The endothelium dependent vasodilator effect of acetylcholine: A characterization of the endothelial relaxing factor with inhibitors of arachidonic acid metabolism. Eur J Pharmacol (in press)

  • Furchgott RF, Zawadzki JV (1980) The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature 288:373–376

    Google Scholar 

  • Greenberg S, Kadowitz PJ, Long JP, Wilson WR (1976) Studies on the nature of a prostaglandin receptor in canine and rabbit vascular smooth muscle. Circ Res 1:66–76

    Google Scholar 

  • Jobke A, Peskar BA, Peskar BM (1973) On the specifity of antisera against prostaglandins A2 and E2. FEBS Lett 37:192–196

    Google Scholar 

  • Kalsner S (1978) The effect of hypoxia on prostaglandin output and on tone in isolated coronary arteries. Can J Physiol Pharmacol 55:882–887

    Google Scholar 

  • Kalsner S (1978) Prostaglandin mediated relaxation of coronary artery strips under hypoxia. Prostaglandins Med 1:231–239

    Google Scholar 

  • Kirstein A (1979) Cardiac prostacyclin release: Stimulation by hypoxia and various agents. Scand J Haematol 34:105–111

    Google Scholar 

  • Kontos HA (1971) Role of hypercapnic acidosis in the local regulation of blood flow in skeletal muscle. Circ Res 28 (Suppl 1): 98–105

    Google Scholar 

  • Lands WEM, Sauter J, Stone GW (1978) Oxygen requirement for prostaglandin biosynthesis. Prostaglandins Med 1:117–120

    Google Scholar 

  • Lapetina EG (1982) Regulation of arachidonic acid production: role of phospholipases C and A2. Trends Pharmacol Sci 3:115–118

    Google Scholar 

  • Machleidt C, Förstermann U, Anhut H, Hertting G (1981) Formation and elimination of prostacyclin metabolites in the cat in vivo as determined by radioimmunoassay of unextracted plasma. Eur J Pharmacol 74:19–26

    Google Scholar 

  • Moncada S, Herman AG, Higgs EA, Vane JR (1977) Differential formation of prostacyclin (PGX or PGI2) by layers of the arterial wall. An explanation for the anti-thrombotic properties of vascular endothelium. Thromb Res 11:323–344

    Google Scholar 

  • Needleman P, Key SL, Isakson PC, Kulkarni PA (1975) Relationship between oxygen tension, coronary vasodilation and prostaglandin biosynthesis in the isolated rabbit heart. Prostaglandins 9:123–135

    Google Scholar 

  • Nees S, Gerlach E (1983) Adenine nucleotide and adenosine metabolism in cultured coronary endothelial cells: formation and release of adenine compounds and possible functional implications. In: Berne RM, Rall TW, Rubio R (eds) Regulatory function of adenosine. Martinus Nijhoff Publishers, Boston London, pp 347–360

    Google Scholar 

  • Palik I, Koltai MZS, Hadhazy P, Malomvölgyi B, Wagner M, Pogatsa G (1982) Effects of prostaglandins E2, I2 and F on the tone of isolated coronary arteries from alloxan-diabetic dogs. Prostaglandins Med 8:607–614

    Google Scholar 

  • Roberts AM, Messina EJ, Kaley G (1981) Prostacyclin (PGI2) mediates hypoxic relaxation of bovine coronary arterial strips. Prostaglandins 21:555–559

    Google Scholar 

  • Simmet T, Förstermann U, Peskar BA (1980) Effect of exogenous and endogenous prostacyclin on the contractility of rabbit splenic capsular smooth muscle. Naunyn-Schmiedeberg's Arch Pharmacol 312:245–253

    Google Scholar 

  • Van de Voorde J, Leusen I (1983) Role of the endothelium in the vasodilator response of rat thoracic aorta to histamine. Eur J Pharmacol 87:113–120

    Google Scholar 

  • Wennmalm A (1979) prostacyclin-dependent coronary vasodilation in rabbit and guinea pig hearts. Acta Physiol Scand 106:47–52

    Google Scholar 

  • Wennmalm A, Pham-Huu-Chanh, Junstad M (1974) Hypoxia causes prostaglandin release from perfused rabbit hearts. Acta Physiol Scand 91:133–135

    Google Scholar 

  • Wolfe LS, Rostworowski K, Manku M (1979) Measurement of prostaglandin synthesis and release from rat aortic tissue and from the perfused mesenteric artery by gas-chromatographymass-spectrometric methods. In: Vane JR, Bergström S (eds) Prostacyclin. Raven Press, New York, pp 113–118

    Google Scholar 

  • Wong PYK, Sun F, McGiff JC (1978) Metabolism of prostacyclin in blood vessels. J Biol Chem 253:5555–5557

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

Supported by the Deutsche Forschungsgemeinschaft (Bu 436/2-1)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Busse, R., Förstermann, U., Matsuda, H. et al. The role of prostaglandins in the endothelium-mediated vasodilatory response to hypoxia. Pflugers Arch. 401, 77–83 (1984). https://doi.org/10.1007/BF00581536

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00581536

Key words

Navigation