PT  - JOURNAL ARTICLE
AU  - Rob H. P. Hilgers
AU  - Ger M. J. Janssen
AU  - Gregorio E. Fazzi
AU  - Jo G. R. De Mey
TI  - Twenty-Four-Hour Exposure to Altered Blood Flow Modifies Endothelial Ca<sup>2+</sup>-Activated K<sup>+</sup> Channels in Rat Mesenteric Arteries
AID  - 10.1124/jpet.109.161448
DP  - 2010 Apr 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 210--217
VI  - 333
IP  - 1
4099  - http://jpet.aspetjournals.org/content/333/1/210.short
4100  - http://jpet.aspetjournals.org/content/333/1/210.full
SO  - J Pharmacol Exp Ther2010 Apr 01; 333
AB  - We tested the hypothesis that changes in arterial blood flow modify the function of endothelial Ca2+-activated K+ channels [calcium-activated K+ channel (KCa), small-conductance calcium-activated K+ channel (SK3), and intermediate calcium-activated K+ channel (IK1)] before arterial structural remodeling. In rats, mesenteric arteries were exposed to increased [+90%, high flow (HF)] or reduced blood flow [−90%, low flow (LF)] and analyzed 24 h later. There were no detectable changes in arterial structure or in expression level of endothelial nitric-oxide synthase, SK3, or IK1. Arterial relaxing responses to acetylcholine and 3-oxime-6,7-dichlore-1H-indole-2,3-dione (NS309; activator of SK3 and IK1) were measured in the absence and presence of endothelium, NO, and prostanoid blockers, and 6,12,19,20,25,26-hexahydro-5,27:13,18:21,24-trietheno-11,7-metheno-7H-dibenzo [b,n] [1,5,12,16]tetraazacyclotricosine-5,13-diium dibromide (UCL 1684; inhibitor of SK3) or 1-[(2-chlorophenyl)diphenylmethyl]-1H-pyrazole (TRAM-34; inhibitor of IK1). In LF arteries, endothelium-dependent relaxation was markedly reduced, due to a reduction in the endothelium-derived hyperpolarizing factor (EDHF) response. In HF arteries, the balance between the NO/prostanoid versus EDHF response was unaltered. However, the contribution of IK1 to the EDHF response was enhanced, as indicated by a larger effect of TRAM-34 and a larger residual NS309-induced relaxation in the presence of UCL 1684. Reduction of blood flow selectively blunts EDHF relaxation in resistance arteries through inhibition of the function of KCa channels. An increase in blood flow leads to a more prominent role of IK1 channels in this relaxation.