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. 1995 Dec;116(7):3068–3074. doi: 10.1111/j.1476-5381.1995.tb15965.x

The involvement of ATP-sensitive potassium channels and adenosine in the regulation of coronary flow in the isolated perfused rat heart.

M D Randall 1
PMCID: PMC1909199  PMID: 8680745

Abstract

1. The roles of adenosine 5'-triphosphate (ATP)-sensitive potassium channels (KATP) and endogenous adenosine in the regulation of coronary flow have been assessed in the isolated, buffer-perfused heart of the rat. 2. In the presence of glibenclamide 10 microM there was a significant (P < 0.001) reduction in coronary flow from a baseline value of 8.78 +/- 0.76 ml min-1 g-1 to 3.89 +/- 0.59 ml min-1 g-1. This change was accompanied by a significant (P < 0.01) reduction in cardiac mechanical performance as shown by the decrease in the pressure-rate product from 21,487 +/- 2,577 mmHg min-1 to 6,950 +/- 1,104 mmHg min-1. 3. The non-selective adenosine antagonist 8-phenyltheophylline (10 microM) also caused a significant (P < 0.001) reduction in coronary flow from a basal value of 10.4 +/- 0.6 ml min-1 g-1 to 6.32 +/- 0.60 ml min-1 g-1. The subsequent addition of glibenclamide, in the presence of 8-phenyltheophylline, brought about a further significant (P < 0.001) reduction in coronary flow to 3.05 +/- 0.55 ml min-1 g-1 and this value was similar to that in the presence of glibenclamide alone. 4. In hearts perfused under constant flow conditions, exogenous adenosine caused dose-related reductions in coronary perfusion pressure described by a maximum reduction in pressure of 30.7 +/- 3.9 mmHg and an ED50 of 977 +/- 813 pmol. Addition of glibenclamide caused a significant (P < 0.01) increase in coronary perfusion pressure of 44.7 +/- 7.2 mmHg and a significant (P < 0.05) rightward shift of the dose-response curve for the depressor effects of adenosine (ED50 = 13.5 +/- 3.8 nmol), with a depression (P < 0.05) of the maximum (16.3 +/- 2.4 mmHg). 5. In conclusion, both KATP and endogenous adenosine make major contributions towards coronary vascular tone and the regulation of coronary flow in the rat isolated heart. Furthermore, in the coronary vasculature a significant proportion of the vasodilator action of adenosine is mediated through the activation of KATP.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aversano T., Ouyang P., Silverman H. Blockade of the ATP-sensitive potassium channel modulates reactive hyperemia in the canine coronary circulation. Circ Res. 1991 Sep;69(3):618–622. doi: 10.1161/01.res.69.3.618. [DOI] [PubMed] [Google Scholar]
  2. BERNE R. M. Cardiac nucleotides in hypoxia: possible role in regulation of coronary blood flow. Am J Physiol. 1963 Feb;204:317–322. doi: 10.1152/ajplegacy.1963.204.2.317. [DOI] [PubMed] [Google Scholar]
  3. Belloni F. L., Hintze T. H. Glibenclamide attenuates adenosine-induced bradycardia and coronary vasodilatation. Am J Physiol. 1991 Sep;261(3 Pt 2):H720–H727. doi: 10.1152/ajpheart.1991.261.3.H720. [DOI] [PubMed] [Google Scholar]
  4. Berne R. M. The role of adenosine in the regulation of coronary blood flow. Circ Res. 1980 Dec;47(6):807–813. doi: 10.1161/01.res.47.6.807. [DOI] [PubMed] [Google Scholar]
  5. Billman G. E., Avendano C. E., Halliwill J. R., Burroughs J. M. The effects of the ATP-dependent potassium channel antagonist, glyburide, on coronary blood flow and susceptibility to ventricular fibrillation in unanesthetized dogs. J Cardiovasc Pharmacol. 1993 Feb;21(2):197–204. doi: 10.1097/00005344-199302000-00003. [DOI] [PubMed] [Google Scholar]
  6. Bouchard J. F., Dumont E., Lamontagne D. Evidence that prostaglandins I2, E2, and D2 may activate ATP sensitive potassium channels in the isolated rat heart. Cardiovasc Res. 1994 Jun;28(6):901–905. doi: 10.1093/cvr/28.6.901. [DOI] [PubMed] [Google Scholar]
  7. Clapp L. H., Gurney A. M. ATP-sensitive K+ channels regulate resting potential of pulmonary arterial smooth muscle cells. Am J Physiol. 1992 Mar;262(3 Pt 2):H916–H920. doi: 10.1152/ajpheart.1992.262.3.H916. [DOI] [PubMed] [Google Scholar]
  8. Dart C., Standen N. B. Adenosine-activated potassium current in smooth muscle cells isolated from the pig coronary artery. J Physiol. 1993 Nov;471:767–786. doi: 10.1113/jphysiol.1993.sp019927. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Imamura Y., Tomoike H., Narishige T., Takahashi T., Kasuya H., Takeshita A. Glibenclamide decreases basal coronary blood flow in anesthetized dogs. Am J Physiol. 1992 Aug;263(2 Pt 2):H399–H404. doi: 10.1152/ajpheart.1992.263.2.H399. [DOI] [PubMed] [Google Scholar]
  10. Jackson W. F. Arteriolar tone is determined by activity of ATP-sensitive potassium channels. Am J Physiol. 1993 Nov;265(5 Pt 2):H1797–H1803. doi: 10.1152/ajpheart.1993.265.5.H1797. [DOI] [PubMed] [Google Scholar]
  11. Kirsch G. E., Codina J., Birnbaumer L., Brown A. M. Coupling of ATP-sensitive K+ channels to A1 receptors by G proteins in rat ventricular myocytes. Am J Physiol. 1990 Sep;259(3 Pt 2):H820–H826. doi: 10.1152/ajpheart.1990.259.3.H820. [DOI] [PubMed] [Google Scholar]
  12. Komaru T., Lamping K. G., Eastham C. L., Dellsperger K. C. Role of ATP-sensitive potassium channels in coronary microvascular autoregulatory responses. Circ Res. 1991 Oct;69(4):1146–1151. doi: 10.1161/01.res.69.4.1146. [DOI] [PubMed] [Google Scholar]
  13. Lamping K. G., Bloom E. N., Harrison D. G. Regulation of native collateral vessel dilation after coronary occlusion in the dog. Am J Physiol. 1994 Feb;266(2 Pt 2):H769–H778. doi: 10.1152/ajpheart.1994.266.2.H769. [DOI] [PubMed] [Google Scholar]
  14. Merkel L. A., Lappe R. W., Rivera L. M., Cox B. F., Perrone M. H. Demonstration of vasorelaxant activity with an A1-selective adenosine agonist in porcine coronary artery: involvement of potassium channels. J Pharmacol Exp Ther. 1992 Feb;260(2):437–443. [PubMed] [Google Scholar]
  15. Miwa A., Jinno Y., Yokoyama T., Izawa T., Ogawa N. Pharmacological analysis of the effect of KRN2391 on coronary vasculature in perfused rat heart. Gen Pharmacol. 1994 May;25(3):471–474. doi: 10.1016/0306-3623(94)90200-3. [DOI] [PubMed] [Google Scholar]
  16. Moreau R., Komeichi H., Kirstetter P., Yang S., Aupetit-Faisant B., Cailmail S., Lebrec D. Effects of glibenclamide on systemic and splanchnic haemodynamics in conscious rats. Br J Pharmacol. 1994 Jun;112(2):649–653. doi: 10.1111/j.1476-5381.1994.tb13124.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Nakae I., Quan L., Sugimoto Y., Tsutamoto T., Kinoshita M. Glibenclamide-induced oscillation of canine coronary artery is independent of myocardial ischemia. J Cardiovasc Pharmacol. 1994 Mar;23(3):473–479. [PubMed] [Google Scholar]
  18. Narishige T., Egashira K., Akatsuka Y., Katsuda Y., Numaguchi K., Sakata M., Takeshita A. Glibenclamide, a putative ATP-sensitive K+ channel blocker, inhibits coronary autoregulation in anesthetized dogs. Circ Res. 1993 Oct;73(4):771–776. doi: 10.1161/01.res.73.4.771. [DOI] [PubMed] [Google Scholar]
  19. Nelson M. T., Quayle J. M. Physiological roles and properties of potassium channels in arterial smooth muscle. Am J Physiol. 1995 Apr;268(4 Pt 1):C799–C822. doi: 10.1152/ajpcell.1995.268.4.C799. [DOI] [PubMed] [Google Scholar]
  20. Nichols C. G., Lederer W. J. Adenosine triphosphate-sensitive potassium channels in the cardiovascular system. Am J Physiol. 1991 Dec;261(6 Pt 2):H1675–H1686. doi: 10.1152/ajpheart.1991.261.6.H1675. [DOI] [PubMed] [Google Scholar]
  21. Niiya K., Uchida S., Tsuji T., Olsson R. A. Glibenclamide reduces the coronary vasoactivity of adenosine receptor agonists. J Pharmacol Exp Ther. 1994 Oct;271(1):14–19. [PubMed] [Google Scholar]
  22. Noma A. ATP-regulated K+ channels in cardiac muscle. Nature. 1983 Sep 8;305(5930):147–148. doi: 10.1038/305147a0. [DOI] [PubMed] [Google Scholar]
  23. Randall M. D., McCulloch A. I. The involvement of ATP-sensitive potassium channels in beta-adrenoceptor-mediated vasorelaxation in the rat isolated mesenteric arterial bed. Br J Pharmacol. 1995 Jun;115(4):607–612. doi: 10.1111/j.1476-5381.1995.tb14975.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Randall M. D., Ujiie H., Griffith T. M. Modulation of vasodilatation to levcromakalim by adenosine analogues in the rabbit ear: an explanation for hypoxic augmentation. Br J Pharmacol. 1994 May;112(1):49–54. doi: 10.1111/j.1476-5381.1994.tb13027.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Samaha F. F., Heineman F. W., Ince C., Fleming J., Balaban R. S. ATP-sensitive potassium channel is essential to maintain basal coronary vascular tone in vivo. Am J Physiol. 1992 May;262(5 Pt 1):C1220–C1227. doi: 10.1152/ajpcell.1992.262.5.C1220. [DOI] [PubMed] [Google Scholar]
  26. Sturgess N. C., Ashford M. L., Cook D. L., Hales C. N. The sulphonylurea receptor may be an ATP-sensitive potassium channel. Lancet. 1985 Aug 31;2(8453):474–475. doi: 10.1016/s0140-6736(85)90403-9. [DOI] [PubMed] [Google Scholar]
  27. Xu J., Wang L., Hurt C. M., Pelleg A. Endogenous adenosine does not activate ATP-sensitive potassium channels in the hypoxic guinea pig ventricle in vivo. Circulation. 1994 Mar;89(3):1209–1216. doi: 10.1161/01.cir.89.3.1209. [DOI] [PubMed] [Google Scholar]
  28. von Beckerath N., Cyrys S., Dischner A., Daut J. Hypoxic vasodilatation in isolated, perfused guinea-pig heart: an analysis of the underlying mechanisms. J Physiol. 1991 Oct;442:297–319. doi: 10.1113/jphysiol.1991.sp018794. [DOI] [PMC free article] [PubMed] [Google Scholar]

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