title: Inhibition of Myogenic Tone in Rat Cremaster and Cerebral Arteries by SKA-31, an Activator of Endothelial KCa2.3 and KCa3.1 Channels.
abstract: Endothelial KCa2.3 and KCa3.1 channels contribute to the regulation of myogenic tone in resistance arteries by Ca(2+)-mobilizing vasodilatory hormones. To define further the functional role of these channels in distinct vascular beds, we have examined the vasodilatory actions of the KCa channel activator SKA-31 in myogenically active rat cremaster and middle cerebral arteries. Vessels pressurized to 70 mm Hg constricted by 80-100 μm (ie, 25%-45% of maximal diameter). SKA-31 (10 μM) inhibited myogenic tone by 80% in cremaster and ∼65% in middle cerebral arteries, with IC50 values of ∼2 μM in both vessels. These vasodilatory effects were largely prevented by the KCa2.3 blocker UCL1684 and the KCa3.1 blocker TRAM-34 and abolished by endothelial denudation. Preincubation with N(G) nitro L-arginine methyl ester (L-NAME, 0.1 mM) did not affect the inhibitory response to SKA-31, but attenuated the ACh-evoked dilation by ∼45%. Penitrem-A, a blocker of BK(Ca) channels, did not alter SKA-31 evoked vasodilation but did reduce the inhibition of myogenic tone by ACh, the BKCa channel activator NS1619, and sodium nitroprusside. Collectively, these data demonstrate that SKA-31 produces robust inhibition of myogenic tone in resistance arteries isolated from distinct vascular beds in an endothelium-dependent manner.
authors: *Department of Physiology and Pharmacology, University of Calgary, Calgary, Alberta, Canada; †Department of Pharmacology, University of California Davis, Davis, CA; and ‡Department of Medical Pharmacology and Physiology, Dalton Cardiovascular Research Center, University of Missouri, Columbia, MO.
authors: Ramesh C
authors: RC
authors: Mishra
authors: Heike
authors: H
authors: Wulff
authors: Michael A
authors: MA
authors: Hill
authors: Andrew P
authors: AP
authors: Braun
mesh_terms: D000818:Animals; D052160:Benzothiazoles / Q000494:pharmacology*; D002536:Cerebral Arteries / Q000187:drug effects* / Q000502:physiology; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels / Q000819:agonists* / Q000502:physiology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D051640:Small-Conductance Calcium-Activated Potassium Channels / Q000819:agonists* / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology
chemical_list: D052160:Benzothiazoles; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels; C496901:Kcnn3 protein, rat; C491575:Kcnn4 protein, rat; D051640:Small-Conductance Calcium-Activated Potassium Channels; C535212:naphtho(1,2-d)thiazol-2-ylamine