Nonspecific Inhibition of Myogenic Tone by PD98059, a MEK1 Inhibitor, in Rat Middle Cerebral Arteries

Abstract Activation of MAP kinase kinase, also called ERK kinase (MEK), may lead to desinhibition of thin filament regulatory proteins and we therefore investigated the acute effects of the potent MEK inhibitor, PD98059 on the contractile properties of pressurized rat middle cerebral arteries. Cerebral arteries (diameter 100-150 μm) were mounted on a pressure myograph and PD98059 (10 μM, 40 μM) significantly inhibited (15% and 64%) myogenic tone (P 2+ (0.4-1.6 mM) increased myogenic tone to ∼50% of constriction at 80 mmHg. This effect was inhibited by PD98059 (P 2+ entry in vascular smooth muscle.