SKA‐31, an opener of SK Ca and IK Ca channels, inhibits myogenic tone in rat cerebral and cremaster arteries

We have previously reported that stimulated Ca 2+ mobilization and nitric oxide (NO) synthesis in isolated endothelial cells and agonist‐induced inhibition of myogenic tone in small resistance arteries are directly affected by pharmacological blockade or activation of Ca 2+ ‐activated small and intermediate conductance K + channels (SK Ca and IK Ca ) in vascular endothelium. To characterize this regulatory process further, we have examined the actions of a novel K Ca channel opener (SKA‐31) on myogenically active cremaster and middle cerebral arteries pressurized to 70 mm Hg. Pressurized vessels constricted by 60–100 microns (i.e. 25–45% of their maximal luminal diameter) and we observed that SKA‐31 dose‐dependently (0.3–10 μM) inhibited myogenic tone by 50–60%, which was comparable to the inhibition produced by 0.5 μM acetylcholine (ACh) in the same vessels. Pre‐incubation with the NO synthase inhibitor L‐NAME (0.1 mM) attenuated the dilatory response to ACh in cerebral and cremaster vessels by ~45%, but did not affect the responses to SKA‐31. These data indicate SKA‐31 has the ability to inhibit myogenic tone in small resistant arteries independent of vasodilatory agonists. This class of compound and its mechanism of action may thus be beneficial in disease states where endothelial NO bioavailability is compromised.