Influence of gender on K+-induced cerebral vasodilatation

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 mu mol/L) or acetylcholine (ACh, 1 and 10 mu mol/L) did not differ between the genders. The selective K-IR channel inhibitor barium ion (30 mu mol/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 approximate to50% in both groups. Ovariectomy of female rats resulted in smaller vasodilator effects of K+, and chronic treatment of these rats with 17beta-estradiol (0.01 mg/kg per day for 7 days) normalized K+-induced vasodilatation. Furthermore, the selective M2 muscarinic ACh receptor antagonist methoctramine (1 mumol/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.