Cerebrovascular alterations in mice lacking neuronal nitric oxide synthase gene expression.
Nitric oxide (NO) is known to mediate increases in regional cerebral blood flow elicited by CO2 inhalation. In mice with deletion of the gene for neuronal NO synthase (NOS), CO2 inhalation augments cerebral blood flow to the same extent as in wild-type mice. However, unlike wild-type mice, the increased flow in mutants is not blocked by the NOS inhibition, N omega-nitro-L-arginine, and CO2 exposure fails to increase brain levels of cGMP. Topical acetylcholine elicits vasodilation in the mutants which is blocked by N omega-nitro-L-arginine, indicating normal functioning of endothelial NOS. Moreover, immunohistochemical staining for endothelial NOS is normal in the mutants. Thus, following loss of neuronal NOS, the cerebral circulatory response is maintained by a compensatory system not involving NO.
Irikura
K
K
Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston 02114, USA.
Huang
P L
PL
Ma
J
J
Lee
W S
WS
Dalkara
T
T
Fishman
M C
MC
Dawson
T M
TM
Snyder
S H
SH
Moskowitz
M A
MA
D000109:Acetylcholine / Q000494:pharmacology; D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors / Q000172:deficiency* / Q000235:genetics / Q000302:isolation & purification; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000201:enzymology / Q000502:physiology* / Q000601:surgery; D002245:Carbon Dioxide / Q000494:pharmacology; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology*; D006152:Cyclic GMP / Q000032:analysis; D004730:Endothelium, Vascular / Q000201:enzymology; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D019331:NG-Nitroarginine Methyl Ester; D009474:Neurons / Q000201:enzymology*; D019001:Nitric Oxide Synthase; D019335:Nitroarginine; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology*; D012886:Skull / Q000601:surgery; D014018:Tissue Distribution; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
D002245:Carbon Dioxide; D019335:Nitroarginine; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D006152:Cyclic GMP; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester