Interaction between ATP-Sensitive K+ Channels and Nitric Oxide on Pial Arterioles in Piglets

Abstract

The interaction between ATP-sensitive K+ channels (KATP) and nitric oxide (NO) was studied in pial arterioles of piglets. We examined the effects of N-nitro-l-arginine methyl ester (l-NAME), a general inhibitor of nitric oxide synthase (NOS), and 7-nitroindazole (7-NI), a selective inhibitor of neuronal NOS, on aprikalim-induced cerebral vasodilation. Topically applied, aprikalim, a selective activator of KATP, dilated arterioles by 11 ± 7% at 10−8 M and 17 ± 6% at 10−6 M. After l-NAME treatment (15 mg/kg, i.v.), the response was reduced (4 ± 4% and 12 ± 7%, respectively; n = 8, p < 0.05). Administration of 7-NI (50 mg/kg, i.p.) did not change pial arteriolar responsiveness to aprikalim. However, both l-NAME and 7-NI reduced the vasodilator responses to 10−4 M N-methyl-d-aspartate (NMDA) (by 73% and by 36%, respectively). Furthermore, 7-NI treatment abolished the glutamate-induced dilatation of pial arterioles. Administration of l-NAME reduced the NOS activity in the cerebral cortex by 88%, whereas the reduction after the 7-NI treatment was 44%. Pretreatment and coadministration of 10−5 M glibenclaminde, a specific inhibitor of KATP or l-NAME administration, did not change the dilatory response to sodium nitroprusside. We conclude that NO may be involved in aprikalim-induced dilation of pial arterioles.