Role of inwardly rectifying K⁺ channels in K⁺-induced cerebral vasodilatation in vivo

Abstract

We tested whether activation of inwardly rectifying K(+) (Kir) channels, Na(+)-K(+)-ATPase, or nitric oxide synthase (NOS) play a role in K(+)-induced dilatation of the rat basilar artery in vivo. When cerebrospinal fluid [K(+)] was elevated from 3 to 5, 10, 15, 20, and 30 mM, a reproducible concentration-dependent vasodilator response was elicited (change in diameter = 9 +/- 1, 27 +/- 4, 35 +/- 4, 43 +/- 12, and 47 +/- 16%, respectively). Responses to K(+) were inhibited by approximately 50% by the Kir channel inhibitor BaCl(2) (30 and 100 microM). In contrast, neither ouabain (1-100 microM, a Na(+)-K(+)-ATPase inhibitor) nor N(G)-nitro-L-arginine (30 microM, a NOS inhibitor) had any effect on K(+)-induced vasodilatation. These concentrations of K(+) also hyperpolarized smooth muscle in isolated segments of basilar artery, and these hyperpolarizations were virtually abolished by 30 microM BaCl(2). RT-PCR experiments confirmed the presence of mRNA for Kir2.1 in the basilar artery. Thus K(+)-induced dilatation of the basilar artery in vivo appears to partly involve hyperpolarization mediated by Kir channel activity and possibly another mechanism that does not involve hyperpolarization, activation of Na(+)-K(+)-ATPase, or NOS.

Exercise training normalizes impaired NOS-dependent responses of cerebral arterioles in type 1 diabetic rats

“…We did not examine a role for EDHF in response to ADP in the present study. However, studies by other investigators (10,12,18,21,64) have suggested that the activation of potassium channels, presumably by EDHF, does not play a significant role in the dilatation of cerebral arterioles to the agonists used in the present study. Regarding responses to NMDA, we and others have shown that NMDA dilates cerebral arterioles via the activation of nNOS and the subsequent synthesis/release of nitric oxide (18 -20, 63).…”

Losartan improves impaired nitric oxide synthase-dependent dilatation of cerebral arterioles in type 1 diabetic rats

“…We did not examine a role for EDHF in responses of cerebral arterioles to ADP, acetylcholine or nitroglycerin in the present study, and thus we cannot exclude the possibility that EDHF may contribute to dilatation of cerebral arterioles to these agonists. However, others (Brayden, 1991;Chrissobolis et al, 2000;Faraci and Heistad, 1993;Taguchi et al, 1995) also have suggested that activation of potassium channels, presumably by EDHF, does not play a significant role in dilatation of cerebral vessels to the agonists used in the present study. Thus, we suggest that dilatation of cerebral arterioles to the agonists used in the present study primarily involves the synthesis/release of nitric oxide, presumably via activation of eNOS.…”

Chronic resveratrol treatment restores vascular responsiveness of cerebral arterioles in type 1 diabetic rats

“…synthesis/release of an endothelium-derived hyperpolarizing factor (EDHF) (27,56). We did not examine a role for EDHF in response to ADP in the present study, but studies by other investigators (9,10,16,19,51) have suggested that the activation of potassium channels, presumably by EDHF, does not play a significant role in the dilatation of cerebral arterioles to the agonists used in the present study.…”