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. 1991 Apr;435:163–173. doi: 10.1113/jphysiol.1991.sp018503

Release of endothelial mediators and sympathetic transmitters at different coronary flow rates in rabbit hearts.

A Wennmalm 1, G Benthin 1, E Karwatowska-Prokopczuk 1, J Lundberg 1, A S Petersson 1
PMCID: PMC1181455  PMID: 1685187

Abstract

1. The release of three endothelial mediators, namely, endothelial-derived relaxing factor (EDRF), prostacyclin (PGI2) and endothelin, and of two sympathetic neurotransmitters, noradrenaline and neuropeptide Y (NPY), from resting or sympathetically stimulated rabbit Langendorff hearts was investigated at normal or elevated coronary flow. The sympathetic nerves to the hearts were stimulated at 5 Hz for 30 s and the cardiac effluent was analysed for nitrite (metabolite of EDRF) with electron paramagnetic resonance spectrometry, for 6-keto-PGF1 alpha (metabolite of PGI2) with gas chromatography/mass spectrometry, for endothelin- and NPY-like immunoreactivity with radioimmunoassay, and for noradrenaline and purines with liquid chromatography. 2. During perfusion of the hearts at normal flow (35 +/- 1.4 ml min-1) the effluent concentration of nitrite was 0.15 +/- 0.02 microM, that of 6-keto-PGF1 alpha 0.74 +/- 0.08 nM, and that of endothelin-like immunoreactivity 0.18 +/- 0.01 pM. Nerve stimulation augmented the release of 6-keto-PGF1 alpha from 76 +/- 8 to 99 +/- 10 pmol (3 min)-1 (P less than 0.05), but did not affect the release of nitrite or endothelin-like immunoreactivity. Nerve stimulation also facilitated the outflow of noradrenaline and of NPY-like immunoreactivity by 52 +/- 11 pmol (3 min)-1 and 19 +/- 7 fmol (3 min)-1, respectively. 3. Elevation of the coronary flow to 79 +/- 3.2 ml min-1 did not affect the effluent concentrations of nitrite, 6-keto-PGF1 alpha and endothelin-like immunoreactivity, implying that their outflows were augmented. Sympathetic stimulation at elevated coronary flow did not further augment the outflow of endothelial mediators or of NPY-like immunoreactivity, but increased the outflow of noradrenaline by 62 +/- 12%, in comparison to stimulation at normal flow. Perfusion of the heart with the noradrenaline uptake blocker desipramine (5 microM) completely abolished the promoting effecting of elevated coronary flow on noradrenaline outflow during sympathetic stimulation. 4. These data indicate that an increase in coronary flow in perfused rabbit hearts is paralleled by a corresponding facilitation of the formation of the endothelial mediators, EDRF, prostacyclin and endothelin. Such an elevation of mediator formation does not affect nerve stimulation-induced release of sympathetic transmitters in the heart.

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Selected References

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  1. Amezcua J. L., Palmer R. M., de Souza B. M., Moncada S. Nitric oxide synthesized from L-arginine regulates vascular tone in the coronary circulation of the rabbit. Br J Pharmacol. 1989 Aug;97(4):1119–1124. doi: 10.1111/j.1476-5381.1989.tb12569.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Cernacek P., Stewart D. J. Immunoreactive endothelin in human plasma: marked elevations in patients in cardiogenic shock. Biochem Biophys Res Commun. 1989 Jun 15;161(2):562–567. doi: 10.1016/0006-291x(89)92636-3. [DOI] [PubMed] [Google Scholar]
  3. Edlund A., Fredholm B. B., Patrignani P., Patrono C., Wennmalm A., Wennmalm M. Release of two vasodilators, adenosine and prostacyclin, from isolated rabbit hearts during controlled hypoxia. J Physiol. 1983 Jul;340:487–501. doi: 10.1113/jphysiol.1983.sp014775. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Fredholm B. B., Sollevi A. The release of adenosine and inosine from canine subcutaneous adipose tissue by nerve stimulation and noradrenaline. J Physiol. 1981;313:351–367. doi: 10.1113/jphysiol.1981.sp013670. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Furchgott R. F., Zawadzki J. V. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature. 1980 Nov 27;288(5789):373–376. doi: 10.1038/288373a0. [DOI] [PubMed] [Google Scholar]
  6. Förstermann U., Trogisch G., Busse R. Species-dependent differences in the nature of endothelium-derived vascular relaxing factor. Eur J Pharmacol. 1984 Nov 27;106(3):639–643. doi: 10.1016/0014-2999(84)90071-2. [DOI] [PubMed] [Google Scholar]
  7. Griffith T. M., Edwards D. H., Lewis M. J., Newby A. C., Henderson A. H. The nature of endothelium-derived vascular relaxant factor. Nature. 1984 Apr 12;308(5960):645–647. doi: 10.1038/308645a0. [DOI] [PubMed] [Google Scholar]
  8. Gryglewski R. J., Bunting S., Moncada S., Flower R. J., Vane J. R. Arterial walls are protected against deposition of platelet thrombi by a substance (prostaglandin X) which they make from prostaglandin endoperoxides. Prostaglandins. 1976 Nov;12(5):685–713. doi: 10.1016/0090-6980(76)90047-2. [DOI] [PubMed] [Google Scholar]
  9. Hjemdahl P., Daleskog M., Kahan T. Determination of plasma catecholamines by high performance liquid chromatography with electrochemical detection: comparison with a radioenzymatic method. Life Sci. 1979 Jul 9;25(2):131–138. doi: 10.1016/0024-3205(79)90384-9. [DOI] [PubMed] [Google Scholar]
  10. Isakson P. C., Raz A., Denny S. E., Pure E., Needleman P. A novel prostaglandin is the major product of arachidonic acid metabolism in rabbit heart. Proc Natl Acad Sci U S A. 1977 Jan;74(1):101–105. doi: 10.1073/pnas.74.1.101. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Karwatowska-Prokopczuk E., Ciabattoni G., Wennmalm A. Effect of adenosine on the formation of prostacyclin in the rabbit isolated heart. Br J Pharmacol. 1988 Jul;94(3):721–728. doi: 10.1111/j.1476-5381.1988.tb11581.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Karwatowska-Prokopczuk E., Ciabattoni G., Wennmalm A. Effects of hydrodynamic forces on coronary production of prostacyclin and purines. Am J Physiol. 1989 Jun;256(6 Pt 2):H1532–H1538. doi: 10.1152/ajpheart.1989.256.6.H1532. [DOI] [PubMed] [Google Scholar]
  13. Karwatowska-Prokopczuk E., Wennmalm A. Effects of endothelin on coronary flow, mechanical performance, oxygen uptake, and formation of purines and on outflow of prostacyclin in the isolated rabbit heart. Circ Res. 1990 Jan;66(1):46–54. doi: 10.1161/01.res.66.1.46. [DOI] [PubMed] [Google Scholar]
  14. Karwatowska-Prokopczuk E., Wennmalm A. Endothelium-derived constricting factor(s): the last novelty--endothelin. Clin Physiol. 1990 Mar;10(2):113–121. doi: 10.1111/j.1475-097x.1990.tb00245.x. [DOI] [PubMed] [Google Scholar]
  15. Kelm M., Schrader J. Nitric oxide release from the isolated guinea pig heart. Eur J Pharmacol. 1988 Oct 18;155(3):317–321. doi: 10.1016/0014-2999(88)90522-5. [DOI] [PubMed] [Google Scholar]
  16. Koyama H., Tabata T., Nishzawa Y., Inoue T., Morii H., Yamaji T. Plasma endothelin levels in patients with uraemia. Lancet. 1989 May 6;1(8645):991–992. doi: 10.1016/s0140-6736(89)92631-7. [DOI] [PubMed] [Google Scholar]
  17. Löffelholz K., Muscholl E. A muscarinic inhibition of the noradrenaline release evoked by postganglionic sympathetic nerve stimulation. Naunyn Schmiedebergs Arch Pharmakol. 1969;265(1):1–15. doi: 10.1007/BF01417206. [DOI] [PubMed] [Google Scholar]
  18. Palmer R. M., Ferrige A. G., Moncada S. Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature. 1987 Jun 11;327(6122):524–526. doi: 10.1038/327524a0. [DOI] [PubMed] [Google Scholar]
  19. Pernow J., Hemsén A., Lundberg J. M. Tissue specific distribution, clearance and vascular effects of endothelin in the pig. Biochem Biophys Res Commun. 1989 Jun 15;161(2):647–653. doi: 10.1016/0006-291x(89)92648-x. [DOI] [PubMed] [Google Scholar]
  20. ROSELL S., KOPIN I. J., AXELROD J. FATE OF H3-NORADRENALINE IN SKELETAL MUSCLE BEFORE AND FOLLOWING SYMPATHETIC STIMULATION. Am J Physiol. 1963 Aug;205:317–321. doi: 10.1152/ajplegacy.1963.205.2.317. [DOI] [PubMed] [Google Scholar]
  21. Radomski M. W., Palmer R. M., Moncada S. Comparative pharmacology of endothelium-derived relaxing factor, nitric oxide and prostacyclin in platelets. Br J Pharmacol. 1987 Sep;92(1):181–187. doi: 10.1111/j.1476-5381.1987.tb11310.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Theodorsson-Norheim E., Hemsén A., Lundberg J. M. Radioimmunoassay for neuropeptide Y (NPY): chromatographic characterization of immunoreactivity in plasma and tissue extracts. Scand J Clin Lab Invest. 1985 Jun;45(4):355–365. doi: 10.3109/00365518509161019. [DOI] [PubMed] [Google Scholar]
  23. Vanhoutte P. M. Endothelium and control of vascular function. State of the Art lecture. Hypertension. 1989 Jun;13(6 Pt 2):658–667. doi: 10.1161/01.hyp.13.6.658. [DOI] [PubMed] [Google Scholar]
  24. Wennmalm A., Karwatowska-Prokopczuk E., Wennmalm M. Role of the coronary endothelium in the regulation of sympathetic transmitter release in isolated rabbit hearts. Acta Physiol Scand. 1989 May;136(1):81–87. doi: 10.1111/j.1748-1716.1989.tb08632.x. [DOI] [PubMed] [Google Scholar]
  25. Wennmalm A., Lanne B., Petersson A. S. Detection of endothelial-derived relaxing factor in human plasma in the basal state and following ischemia using electron paramagnetic resonance spectrometry. Anal Biochem. 1990 Jun;187(2):359–363. doi: 10.1016/0003-2697(90)90470-t. [DOI] [PubMed] [Google Scholar]
  26. Wennmalm A. Prostacyclin-dependent coronary vasodilation in rabbit and guinea pig hearts. Acta Physiol Scand. 1979 May;106(1):47–52. doi: 10.1111/j.1748-1716.1979.tb06368.x. [DOI] [PubMed] [Google Scholar]
  27. Wennmalm A. Prostaglandin-mediated inhibition of noradrenaline release. VI. On the intra-cardiac source of prostaglandins released from isolated rabbit hearts. Acta Physiol Scand. 1979 Feb;105(2):254–256. doi: 10.1111/j.1748-1716.1979.tb06339.x. [DOI] [PubMed] [Google Scholar]
  28. Wennmalm M., FitzGerald G. A., Wennmalm A. Prostacyclin as neuromodulator in the sympathetically stimulated rabbit heart. Prostaglandins. 1987 May;33(5):675–691. doi: 10.1016/0090-6980(87)90034-7. [DOI] [PubMed] [Google Scholar]
  29. Yanagisawa M., Kurihara H., Kimura S., Tomobe Y., Kobayashi M., Mitsui Y., Yazaki Y., Goto K., Masaki T. A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature. 1988 Mar 31;332(6163):411–415. doi: 10.1038/332411a0. [DOI] [PubMed] [Google Scholar]
  30. de Deckere E. A., Nugteren D. H., Ten Hoor F. Prostacyclin is the major prostaglandin released from the isolated perfused rabbit and rat heart. Nature. 1977 Jul 14;268(5616):160–163. doi: 10.1038/268160a0. [DOI] [PubMed] [Google Scholar]

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