Inhibitors of gap junctions attenuate myogenic tone in cerebral arteries

The effects of two structurally distinct inhibitors of gap junction communication were studied by using three different forms of vasoconstriction in pressurized rat middle cerebral arteries. The sensitivity of myogenic tone (at 60 mmHg), vasopressin-induced tone (10 nM, at 20 mmHg), and depolarizing solution-induced tone (80 mM K+, at 20 mmHg) to inhibition by heptanol (1.0 μM to 3.0 mM) or 18α-glycyrrhetinic acid (18α-GA, 1.0 to 50 μM) were determined. Pressure-induced myogenic tone was inhibited by heptanol (IC50 = 0.75 ± 0.09 mM) and 18α-GA (∼30 μM). Vasopressin-induced vasoconstriction was also inhibited by heptanol (IC50= 0.4 ± 0.3 mM) and 18α-GA (>1 μM). Depolarizing solution-induced vasoconstriction was less sensitive to inhibition by heptanol compared to vasopressin (P < 0.01) or pressure-induced constriction (P < 0.05). However, 18α-GA did not inhibit depolarization-induced constriction. Sharp microelectrode experiments on isolated arteries revealed stable membrane potentials, with no detectable ...