The cerebrovascular response to elevated potassium - role of nitric oxide in the in vitro model of isolated rat middle cerebral arteries

We investigated the role of nitric oxide (NO) in the vascular response to h igh extraluminal K+-concentrations in the in vitro model of isolated rat mi ddle cerebral arteries (MCA). Under control conditions, rat MCA dilated at 20, 30, 40 and 60 mM K+. At 80 mM K+, a slight vasoconstriction occurred. T he unspecific NO synthase (NOS)-inhibitor L-omega-nitro-L-arginine (L-NNA) increased the resting tone at 3 mM K+ by 31 +/- 5% (P < 0.01). While the va sodilatative effect of 20 mM K+ was unaffected by L-NNA, NOS-inhibition res ulted in vasoconstriction at <greater than or equal to> 40 mM K+ (P < 0.01) . In presence of L-NNA, the basal vessel diameter was restored by either th e NO-donor S-nitroso-N-acetylpenicillamine (SNAP) or the cell-permeable gua nosine-3',5'-cyclic monophosphate (cGMP) analogue 8-Br-cGMP. Co-application of L-NNA with either SNAP or 8-Br-cGMP resulted in partial restitution of the vasodilatative effect of 40 mM K+, respectively. In presence of the sol uble guanylyl cyclase inhibitor 1 H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-on e (ODQ), the vascular response to 40 mM K+ was abolished. Our findings toge ther with findings from the literature indicate a modulator role of NO at K + <greater than or equal to> 40 mM K+, involving a cGMP-dependent mechanism . (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.