AJP - Heart and Circulatory Physiology, Vol 272, Issue 4 1785-H1790, Copyright © 1997 by American Physiological Society

ARTICLES

Role of activation of calcium-sensitive K+ channels in NO- and hypoxia-induced pial artery vasodilation

W. M. Armstead
Department of Anesthesia, University of Pennsylvania and The Children's Hospital of Philadelphia, 19104, USA.

It has been previously observed that nitric oxide (NO) contributes to hypoxic pial artery dilation and that both sodium nitroprusside (SNP), a releaser of NO, and hypoxia elicit dilation via activation of ATP-sensitive K+ channels in the newborn pig. Other studies, however, have shown that NO activates calcium-sensitive K+ (K(Ca)) channels. The present study, therefore, was designed to investigate the role of K(Ca)-channel activation in NO and hypoxic dilation and to relate this mechanism to the previously observed role of NO in hypoxic dilation in newborn pigs equipped with closed cranial windows. SNP (10(-8) and 10(-6) M) elicited pial artery dilation that was unchanged in the presence of the K(Ca)-channel antagonist iberiotoxin (10(-7) M; 10 +/- 1 and 20 +/- 1 vs. 9 +/- 1 and 20 +/- 2% for 10(-8) and 10(-6) M SNP in the absence and presence of iberiotoxin, respectively). Responses to S-nitroso-N-acetylpenicillamine and 8-bromoguanosine 3',5'-cyclic monophosphate were similarly unchanged by iberiotoxin. In contrast, iberiotoxin attenuated the dilation resulting from moderate and severe hypoxia (arterial PO2 approximately 35 and 25 mmHg, respectively; 27 +/- 1 vs. 21 +/- 2 and 34 +/- 1 vs. 16 +/- 2% for moderate and severe hypoxia in the absence and presence of iberiotoxin, respectively). Iberiotoxin blocked responses to the K(Ca)-channel agonist NS-1619, whereas responses to the ATP-sensitive K+ agonist cromakalim were unchanged (8 +/- 1 and 15 +/- 1 vs. 1 +/- 1 and 1 +/- 1% for 10(-8) and 10(-6) M NS-1619 in the absence and presence of iberiotoxin, respectively). These data show that NO and guanosine 3',5'-cyclic monophosphate do not elicit dilation via K(Ca)-channel activation. However, activation of K(Ca) channels does contribute to hypoxic pial dilation. Finally, these data suggest that substances other than NO are involved in the contribution of K(Ca)-channel activation to hypoxic pial artery dilation.

This article has been cited by other articles:

				D. Gebremedhin, K. Yamaura, and D. R. Harder Role of 20-HETE in the hypoxia-induced activation of Ca2+-activated K+ channel currents in rat cerebral arterial muscle cells Am J Physiol Heart Circ Physiol, January 1, 2008; 294(1): H107 - H120. [Abstract] [Full Text] [PDF]

				A. Kanu and C. W. Leffler Carbon monoxide and Ca2+-activated K+ channels in cerebral arteriolar responses to glutamate and hypoxia in newborn pigs Am J Physiol Heart Circ Physiol, November 1, 2007; 293(5): H3193 - H3200. [Abstract] [Full Text] [PDF]

				W. Pearce Hypoxic regulation of the fetal cerebral circulation J Appl Physiol, February 1, 2006; 100(2): 731 - 738. [Abstract] [Full Text] [PDF]

				B. T. Larsen, H. Miura, O. A. Hatoum, W. B. Campbell, B. D. Hammock, D. C. Zeldin, J. R. Falck, and D. D. Gutterman Epoxyeicosatrienoic and dihydroxyeicosatrienoic acids dilate human coronary arterioles via BKCa channels: implications for soluble epoxide hydrolase inhibition Am J Physiol Heart Circ Physiol, February 1, 2006; 290(2): H491 - H499. [Abstract] [Full Text] [PDF]

				A. Ahmed, C. M. Waters, C. W. Leffler, and J. H. Jaggar Ionic mechanisms mediating the myogenic response in newborn porcine cerebral arteries Am J Physiol Heart Circ Physiol, November 1, 2004; 287(5): H2061 - H2069. [Abstract] [Full Text] [PDF]

				X. Peng, J. R. Carhuapoma, A. Bhardwaj, N. J. Alkayed, J. R. Falck, D. R. Harder, R. J. Traystman, and R. C. Koehler Suppression of cortical functional hyperemia to vibrissal stimulation in the rat by epoxygenase inhibitors Am J Physiol Heart Circ Physiol, November 1, 2002; 283(5): H2029 - H2037. [Abstract] [Full Text] [PDF]

				W. Long, L. Zhang, and L. D. Longo Cerebral artery KATP- and KCa-channel activity and contractility: changes with development Am J Physiol Regulatory Integrative Comp Physiol, December 1, 2000; 279(6): R2004 - R2014. [Abstract] [Full Text] [PDF]

				D. G. Welsh and S. S. Segal Role of EDHF in conduction of vasodilation along hamster cheek pouch arterioles in vivo Am J Physiol Heart Circ Physiol, June 1, 2000; 278(6): H1832 - H1839. [Abstract] [Full Text] [PDF]

				P. Hardy, D. Abran, X. Hou, I. Lahaie, K. G. Peri, P. Asselin, D. R. Varma, and S. Chemtob A Major Role for Prostacyclin in Nitric Oxide–Induced Ocular Vasorelaxation in the Piglet Circ. Res., October 5, 1998; 83(7): 721 - 729. [Abstract] [Full Text] [PDF]

				W. M. Armstead Relationship among NO, the KATP channel, and opioids in hypoxic pial artery dilation Am J Physiol Heart Circ Physiol, September 1, 1998; 275(3): H988 - H994. [Abstract] [Full Text] [PDF]

				W. M. Armstead ATP-dependent K+ channel activation reduces loss of opioid dilation after brain injury Am J Physiol Heart Circ Physiol, May 1, 1998; 274(5): H1674 - H1683. [Abstract] [Full Text] [PDF]

				T. Kasemsri and W. M. Armstead Endothelin impairs ATP-sensitive K+ channel function after brain injury Am J Physiol Heart Circ Physiol, December 1, 1997; 273(6): H2639 - H2647. [Abstract] [Full Text] [PDF]

				W. M. Armstead Brain Injury Impairs ATP-Sensitive K+ Channel Function in Piglet Cerebral Arteries Stroke, November 1, 1997; 28(11): 2273 - 2280. [Abstract] [Full Text]

				C. G. Sobey, D. D. Heistad, and F. M. Faraci Mechanisms of Bradykinin-Induced Cerebral Vasodilatation in Rats : Evidence That Reactive Oxygen Species Activate K+ Channels Stroke, November 1, 1997; 28(11): 2290 - 2295. [Abstract] [Full Text]

				M. J. Wilderman and W. M. Armstead Role of neuronal NO synthase in relationship between NO and opioids in hypoxia-induced pial artery dilation Am J Physiol Heart Circ Physiol, October 1, 1997; 273(4): H1807 - H1815. [Abstract] [Full Text] [PDF]