Background and Purpose--It is not known whether cerebral vasoprotective mechanisms in females include increased function of arterial K⁺ channels. We hypothesized that vasodilator responses mediated by activation of inwardly rectifying K⁺ (K_IR) channels are greater in cerebral arteries of female versus male rats and that this is due to the effects of estrogen.

Methods--Changes in basilar artery diameter were measured with a cranial window preparation in anesthetized Sprague-Dawley rats.

Results--K⁺ (5 and 10 mmol/L) caused greater vasodilatation in females (percent maximum, 21±3% and 58±7%, respectively) versus males (11±1% and 37±4%, respectively; P<0.05). In contrast, vasodilator responses to aprikalim (1 and 3 µmol/L) or acetylcholine (ACh, 1 and 10 µmol/L) did not differ between the genders. The selective K_IR channel inhibitor barium ion (30 µmol/L) decreased basilar artery diameter in males but not females (-7±1% versus -2±1%, P<0.05) and selectively inhibited K⁺-induced vasodilatation by 50% in both groups. Ovariectomy of female rats resulted in smaller vasodilator effects of K⁺, and chronic treatment of these rats with 17-estradiol (0.01 mg/kg per day for 7 days) normalized K+-induced vasodilatation. Furthermore, the selective M2 muscarinic ACh receptor antagonist methoctramine (1 µmol/L) increased responses to K⁺ in males to levels equivalent to responses in females but had no effect on responses to K⁺ in females.

Conclusions--K⁺ is a more powerful vasodilator in the female versus male cerebral circulation. This difference is estrogen dependent and could be due to a lack of M2 muscarinic ACh receptor-induced inhibition of K_IR channel activation by K⁺ in female cerebral arteries.