Augmentation of blood flow through cerebral collaterals by inhibition of nitric oxide synthase.
We examined the influence of nitric oxide (NO) on normal and collateral cerebral blood flow after occlusion of the middle cerebral artery (MCA). Effects of NG-nitro-L-arginine (nitroarginine), an inhibitor of NO synthase, were examined during normotension and hypotension (arterial pressure, 50 mm Hg) in 49 anesthetized dogs. Following a craniotomy, a branch of the MCA was cannulated, and collateral-dependent tissue was identified using the shadow-flow technique. Regional cerebral blood flow was measured with microspheres, and pial artery pressure was measured with a micropipette. Intravenous nitroarginine reduced blood flow to normal cerebrum by approximately 40% (p < 0.05) during normotension and hypotension, with aortic pressure maintained constant after nitroarginine administration. Injection of nitroarginine during hypotension, without control of pressor effects, increased aortic and pial artery pressure approximately twofold. Concurrently, blood flow to normal cerebrum decreased (p < 0.05), while flow to collateral-dependent cerebrum increased (p < 0.05). Phenylephrine was infused during hypotension to increase arterial pressure to values similar to those achieved following nitroarginine. Blood flow to collateral-dependent cerebrum increased (p < 0.05), but flow to normal cerebrum was not altered during infusion of phenylephrine. Thus, inhibition of NO synthase during hypotension increases arterial pressure, decreases blood flow to normal cerebrum, and increases blood flow to collateral-dependent cerebrum. Phenylephrine also increases perfusion pressure and blood flow to collateral-dependent cerebrum, but in contrast to nitroarginine, it does not redistribute blood flow from normal cerebrum.
Muhonen
M G
MG
Division of Neurosurgery (Department of Surgery), University of Iowa College of Medicine, Iowa City 52242.
Heistad
D D
DD
Faraci
F M
FM
Loftus
C M
CM
D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001794:Blood Pressure / Q000502:physiology; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology*; D003097:Collateral Circulation / Q000187:drug effects / Q000502:physiology*; D004285:Dogs; D007022:Hypotension / Q000503:physiopathology; D019001:Nitric Oxide Synthase; D019335:Nitroarginine; D010101:Oxygen Consumption / Q000187:drug effects; D010656:Phenylephrine / Q000494:pharmacology
D010656:Phenylephrine; D019335:Nitroarginine; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases