Influence of gender on K+-induced cerebral vasodilatation.
OBJECTIVE
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 micromol/L) or acetylcholine (ACh, 1 and 10 micromol/L) did not differ between the genders. The selective K(IR) channel inhibitor barium ion (30 micromol/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 approximately 50% 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 micromol/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.
Chrissobolis
Sophocles
S
Department of Pharmacology, University of Melbourne, Parkville, Victoria, Australia.
Sobey
Christopher G
CG
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001464:Barium / Q000494:pharmacology; D001488:Basilar Artery / Q000187:drug effects* / Q000502:physiology; D001921:Brain / Q000098:blood supply*; D002560:Cerebrovascular Circulation / Q000502:physiology; D003959:Diamines / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology; D010052:Ovariectomy; D010847:Picolines / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology*; D024661:Potassium Channels, Inwardly Rectifying / Q000037:antagonists & inhibitors / Q000378:metabolism; D011714:Pyrans / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043585:Receptor, Muscarinic M2 / Q000187:drug effects / Q000378:metabolism; D012737:Sex Factors; D014654:Vascular Patency / Q000187:drug effects* / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
D003959:Diamines; D018727:Muscarinic Antagonists; D010847:Picolines; D024661:Potassium Channels, Inwardly Rectifying; D011714:Pyrans; D043585:Receptor, Muscarinic M2; D014665:Vasodilator Agents; D001464:Barium; C061043:aprikalim; D004958:Estradiol; D000109:Acetylcholine; C054938:methoctramine; D011188:Potassium