Figure 1.

SKA-31 inhibits myogenic tone in pressurized cremaster and middle cerebral arteries. In single cannulated cremaster (panel A) and middle cerebral (panel B) arteries, step-wise increases in intraluminal pressure resulted in the generation of spontaneous myogenic tone and active vasoconstriction. Serial additions of SKA-31 (as indicated by the horizontal bars above the tracing) produced a concentration-dependent inhibition of myogenic tone that was reversible upon SKA-31 washout from the bath. Addition of a near-maximal concentration of acetylcholine (ACh, 3 μM) also produced a rapid and reversible inhibition of myogenic tone. Exposure of the vessel to Kreb’s buffer containing 2 mM EGTA and no added CaCl₂ was performed at the end of the protocol to obtain the maximal passive vessel diameter at 70 mmHg. In panel C, the concentration-response data for SKA-31 evoked inhibition of active tone were fit with a Hill equation (see Materials and Methods), yielding calculated maximal levels of inhibition and IC₅₀ values for SKA-31 action in cremaster arteries (max inhibition = 80.8 %, IC₅₀ = 1.78 ± 0.14 μM, n = 21) and middle cerebral arteries (max inhibition = 64.5%, IC₅₀ = 2.05 ± 0.08 μM, n = 7). The histogram in panel D displays quantification of SKA-31 and ACh-evoked inhibition of myogenic tone in cremaster and middle cerebral arteries, as described under Methods and Materials. Data are presented as mean ± SEM for 21 cremaster and 7 middle cerebral arteries. No difference in the % inhibition of myogenic by SKA-31 at a given concentration was noted between cremaster and cerebral arteries. The asterisk (*) indicates a statistically significant difference compared with the ACh-induced inhibition observed in cremaster arteries, P < 0.05.