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 high extraluminal K(+)-concentrations in the in vitro model of isolated rat middle 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. The 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 vasodilatative effect of 20 mM K(+) was unaffected by L-NNA, NOS-inhibition resulted in vasoconstriction at > or = 40 mM K(+) (P<0.01). In presence of L-NNA, the basal vessel diameter was restored by either the NO-donor S-nitroso-N-acetylpenicillamine (SNAP) or the cell-permeable guanosine-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 soluble guanylyl cyclase inhibitor 1 H-[l,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), the vascular response to 40 mM K(+) was abolished. Our findings together with findings from the literature indicate a modulator role of NO at K(+) > or = 40 mM K(+), involving a cGMP-dependent mechanism.