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Am J Physiol Heart Circ Physiol 279: H2704-H2712, 2000;
0363-6135/00 $5.00
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Vol. 279, Issue 6, H2704-H2712, December 2000

Role of inwardly rectifying K+ channels in K+-induced cerebral vasodilatation in vivo

Sophocles Chrissobolis1, James Ziogas1, Yi Chu2, Frank M. Faraci2, and Christopher G. Sobey1

1 Department of Pharmacology, The University of Melbourne, Parkville, Victoria 3010, Australia; and 2 Departments of Internal Medicine and Pharmacology, Cardiovascular Center, University of Iowa College of Medicine, Iowa City, Iowa 52242

We tested whether activation of inwardly rectifying K+ (Kir) channels, Na+-K+-ATPase, or nitric oxide synthase (NOS) play a role in K+-induced dilatation of the rat basilar artery in vivo. When cerebrospinal fluid [K+] was elevated from 3 to 5, 10, 15, 20, and 30 mM, a reproducible concentration-dependent vasodilator response was elicited (change in diameter = 9 ± 1, 27 ± 4, 35 ± 4, 43 ± 12, and 47 ± 16%, respectively). Responses to K+ were inhibited by ~50% by the Kir channel inhibitor BaCl2 (30 and 100 µM). In contrast, neither ouabain (1-100 µM, a Na+-K+-ATPase inhibitor) nor NG-nitro-L-arginine (30 µM, a NOS inhibitor) had any effect on K+-induced vasodilatation. These concentrations of K+ also hyperpolarized smooth muscle in isolated segments of basilar artery, and these hyperpolarizations were virtually abolished by 30 µM BaCl2. RT-PCR experiments confirmed the presence of mRNA for Kir2.1 in the basilar artery. Thus K+-induced dilatation of the basilar artery in vivo appears to partly involve hyperpolarization mediated by Kir channel activity and possibly another mechanism that does not involve hyperpolarization, activation of Na+-K+-ATPase, or NOS.

barium; basilar artery; nitric oxide synthase; ouabain; sodium-potassium adenosine triphosphatase


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