Abstract
Potassium channels have been demonstrated to modulate myogenic vasoconstriction (1) and are suggested to mediate the vasodilatory effects of hypoxia (2). We have recently demonstrated that hypoxia inhibits the pressure-induced renal afferent arteriolar vasoconstriction. This effect of hypoxia is reversed by 1.0 µM glibenclamide, suggesting that hypoxia inhibits myogenic reactivity by activating ATP-sensitive K channels (3). Activation of this glibenclamide-sensitive vasodilatory mechanism occurred at pO2 levels as high as 60 torr and was not associated with a concurrent elevation in reduced nicotinamide (NADH) arteriolar autofluoresence (3). These observations suggest that hypoxia-induced activation of Katp channels is not mediated by a reduction in arteriolar smooth muscle oxidative phosphorylation. Since these findings could be explained by an indirect coupling of hypoxia to vascular smooth muscle Katp channels (e.g., mediated by released autacoids), we have examined the effects of adenosine, adenosine-receptor blockade and cyclooxygenase inhibition on myogenic reactivity and on the vasodilatory response to hypoxia. Our findings suggest that although adenosine also elicits glibenclamidesensitive vasodilation in this model, hypoxia-induced vasodilation is not prevented by adenosine receptor blockade or cyclooxygenase inhibition. We suggest that during hypoxia, ATP-sensitive K channels are activated through a mechanism independent of adenosine, prostaglandin synthesis or reductions in oxidative production of ATP within the smooth muscle cell. The present article summarizes these findings. Portions of this article have been adapted with permission from reference #3.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsPreview
Unable to display preview. Download preview PDF.
References
Brayden JE, Nelson MT. Regulation of arterial tone by activation of calcium-dependent potassium channels. Science 256: 532–535, 1992
Daut J, Maier-Rudolp W, von Beckerath N, Mehrke G, Gunther K, Goedel-Meiner L. Hypoxic dilation of coronary arteries is mediate by ATP-sensitive potassium channels. Science 247: 1341–1344, 1990.
Loutzenhiser R, Parker M. Hypoxia inhibits myogenic reactivity of renal afferent arterioles by activating ATP-sensitive K+ channels. Circ Res 74(5): in press,1994.
von Beckerath N, Cyrys S, Dischner A, Daut J. Hypoxic vasodilation in isolated perfused guinea-pig heart: an analysis of the underlying mechanisms. J Physiol (London) 442: 297–319, 1991.
Komaru T, Lamping KG, Eastham CL, Dellsperger KC. Role of ATP-sensitive potassium channels in coronary microvascular autoregulatory responses. Circ Res 69: 1146–1151, 1991.
Vanelli G, Hussain SNA. Effects of potassium channel blockers on basal vascular tone and reactive hyperemia of the canine diaphragm. Am J Physiol, 266: H43 - H51, 1994.
Wiener CM, Dunn A, Sylvester JT. ATP-dependent K channels modulate vasoconstrictor responses to severe hypoxia in isolated ferret lungs. J Clin Invest 88: 500–504, 1991.
Noma A. ATP-regulated K channels in cardiac muscle. Nature 305: 147–148, 1983.
Post JM, Jones AW. Stimulation of arterial K efflux by ATP depletion and chromakalim is antagonized by glyburide. Am J Physiol 260: H848 - H854, 1991.
Clapp LH, Gurney AM. ATP-sensitive K channels regulate resting potential of pulmonary arterial smooth muscle cells Am J Physiol 262: H916 - H920, 1992.
Paul RJ. Smooth muscle energetics, Ann Rev Physiol 51: 331–349, 1989.
Lynch RM, Paul RJ. Compartmentation of carbohydrate metabolism in vascular smooth muscle: effects of different energy loading conditions. Am J Physiol 252: C328 - C334, 1987.
Berger EY, Galdston M, Horwitz SA. Effects of anoxic anoxia on the human kidney. J Clin Invest 28: 648–652, 1949.
Sparks HV. Effects of local metabolic factors on vascular smooth muscle. In: Handbook of Physiology, Circulation Section II, eds Bohr DF, Somlyo AP, Sparks HV., 1980, Am Physiol Soc, Baltimore, pages 475–513.
Jobsis FF. Oxidative metabolism at low pO2. Fed Proc 31: 1404–1413, 1972.
Jones DP. Effect of mitochondrial clustering on 02 supply in hepatocytes. Am J Physiol 247: C83 - C89, 1984.
Duchen MR, Biscoe TJ. Mitochondrial function in type I cells isolated from rabbit arterial chemoreceptors. J Physiol (London) 450: 13–31, 1992.
Pohl U. Endothelium cells as part of a vascular oxygen-sensing system: hypoxia-induced release of autacoids. Experimentia 46: 1175–1179, 1990.
Loutzenhiser R, Fei Q, Reslerova, M. Novel (non-Al/A2) adenosine response of the afferent arteriole in the hydronephrotic rat kidney. (Abstract) In Press,12th. International Congress of Pharmacology, 1994.
Hayashi K, Epstein M, Loutzenhiser R. Determinants of the renal actions of atrial natriuretic peptide (ANP): Lack of effect on ANP on pressure-induced vasoconstriction. Circ Res 67: 110, 1990.
Hayashi K, Epstein M, Loutzenhiser R, Forster H. Impaired myogenic responsiveness of the renal afferent arteriole in streptozotocin-induced diabetic rats: role of eicosanoid derangements. J Am Soc Nephrol 2: 1578–1586, 1992.
Cornfield LI, Hu S, Hurt SD, Sills MA. [3H] 2-Phenylaminoadenosine (CH] CV1808) labels a novel adenosine receptor in rat brain. J Pharmacol Exp Ther 263: 552–561, 1992.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1994 Springer Science+Business Media New York
About this chapter
Cite this chapter
Loutzenhiser, R., Parker, M. (1994). Hypoxia and Adenosine Inhibit Myogenic Reactivity by Activating ATP-Sensitive Potassium Channels. In: Halpern, W., Bevan, J., Brayden, J., Dustan, H., Nelson, M., Osol, G. (eds) The Resistance Arteries. Experimental Biology and Medicine, vol 26. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-4757-2296-3_13
Download citation
DOI: https://doi.org/10.1007/978-1-4757-2296-3_13
Publisher Name: Humana Press, Totowa, NJ
Print ISBN: 978-1-61737-008-3
Online ISBN: 978-1-4757-2296-3
eBook Packages: Springer Book Archive