title: The cerebrovascular response to elevated potassium--role of nitric oxide in the in vitro model of isolated rat middle cerebral arteries.
abstract: 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.
authors.affiliation: Department of Experimental Neurology, Humboldt University, Charité Hospital, 10098, Berlin, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Schuh-Hofer
authors.forename: E
authors.initials: E
authors.lastname: Lobsien
authors.forename: R
authors.initials: R
authors.lastname: Brodowsky
authors.forename: J
authors.initials: J
authors.lastname: Vogt
authors.forename: J P
authors.initials: JP
authors.lastname: Dreier
authors.forename: R
authors.initials: R
authors.lastname: Klee
authors.forename: U
authors.initials: U
authors.lastname: Dirnagl
authors.forename: U
authors.initials: U
authors.lastname: Lindauer
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000378:metabolism / Q000503:physiopathology; D002560:Cerebrovascular Circulation / Q000187:drug effects* / Q000502:physiology; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005110:Extracellular Space / Q000378:metabolism*; D008297:Male; D020768:Middle Cerebral Artery / Q000187:drug effects* / Q000378:metabolism; D008954:Models, Biological; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D019335:Nitroarginine / Q000494:pharmacology; D009924:Organ Culture Techniques; D010069:Oxadiazoles / Q000494:pharmacology; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism* / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D026423:S-Nitroso-N-Acetylpenicillamine; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
chemical_list: C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D004791:Enzyme Inhibitors; D010069:Oxadiazoles; D015221:Potassium Channels; D011810:Quinoxalines; D019335:Nitroarginine; C016276:8-bromocyclic GMP; D009569:Nitric Oxide; D026423:S-Nitroso-N-Acetylpenicillamine; D019001:Nitric Oxide Synthase; D010396:Penicillamine; D006152:Cyclic GMP; D011188:Potassium