Influence of Gender on K + -Induced Cerebral Vasodilatation

Abstract

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 17β-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.