Nitric oxide synthesis and regional cerebral blood flow responses to hypercapnia and hypoxia in the rat.
The role of nitric oxide (NO) synthesis in the cerebral hyperemic responses to hypercapnia and hypoxia was investigated in anesthetized rats. Regional CBF (rCBF) measurements were obtained in the cortex (CX), subcortex (SC), brainstem (BS), and cerebellum (CE) using radiolabeled microspheres. The rCBF responses to either hypercapnia (PaCO2 = 70-80 mm Hg) or hypoxia (PaO2 = 40-45 mm Hg) were compared in rat groups studied in the presence and absence of NO synthase inhibition induced via the intravenous infusion of nitro-L-arginine methyl ester (L-NAME, 3 mg kg-1 min-1). Administration of L-NAME under normocapnic/normoxic conditions produced a 40-60% reduction in baseline rCBF values, indicating the presence of a NO "tone" in the cerebral vasculature. Infusion of L-NAME resulted in a substantial attenuation, in all regions measured, of the rCBF increases that normally accompany hypercapnia. In comparing saline-infused to L-NAME-infused rats, the percentage increases in rCBF (from normocapnic baseline values) were 351% versus 166% (CX), 446% versus 199% (SC), 443% versus 206% (BS), and 483% versus 174% (CE), respectively. The rCBF changes from baseline (delta rCBF in ml 100 g-1 min-1) were 488 versus 57 (CX), 570 versus 60 (SC), 434 versus 72 (BS), and 393 versus 45 (CE), respectively. These differences were all statistically significant (p < 0.05). During hypoxia, when compared to rats not given L-NAME, inhibition of NO synthase activity resulted in significantly greater (p < 0.05) percentage increases in rCBF (from normoxic baseline values) in most regions.(ABSTRACT TRUNCATED AT 250 WORDS)
Pelligrino
D A
DA
Department of Anesthesiology, University of Illinois-Chicago.
Koenig
H M
HM
Albrecht
R F
RF
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002560:Cerebrovascular Circulation; D006935:Hypercapnia / Q000503:physiopathology*; D000860:Hypoxia / Q000503:physiopathology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D009569:Nitric Oxide; D001120:Arginine; D019331:NG-Nitroarginine Methyl Ester