Effect of the inhibitor of nitric oxide synthase, NG-nitro-L-arginine methyl ester, on cerebral and myocardial blood flows during hypoxia in the awake dog.
The increase in cerebral blood flow (CBF) elicited by moderate hypoxia in anesthetized animals is little attenuated by nitric oxide (NO) synthase inhibitors. However, in previous studies, the effects of NO synthase inhibitors may have been altered by anesthetics. Consequently, we studied the effects of the NO synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), on cerebral and myocardial blood flows during hypoxia in the awake dog. Regional CBF and myocardial blood flows (MBF) were measured under normoxia and hypoxia in 16 beagle dogs after an intravenous (IV) injection of either saline (control, n = 8) or L-NAME 20 mg/kg (n = 8). One week after thoracotomy for catheter insertion, awake dogs were studied during three periods: normoxia and after 2 and 4 h of normocapanic hypoxia in an environmental chamber (FIO2 = 0.10, FICO2 = 0.035, balance N2). At each stage, a bolus injection of L-NAME or saline was followed 15 min later by left atrial injection of radiolabeled microspheres (141Ce, 103Ru, 46Sc) for regional CBF and MBF. After the dogs were killed, the brain and the heart were fixed in 10% formaldehyde, dissected by region and weighed, and radioactivity was measured in a gamma counter. During hypoxia, Pao2 was approximately 45 mm Hg with normal Paco2. In the control group, CBF increased by 45% after 2 h and 48% after 4 h of hypoxia; MBF increased by 69% and 60%, respectively. L-NAME prevented the CBF increase during hypoxia and the MBF increase after 2 h of hypoxia; after 4 h of hypoxia the measurement of MBF was confounded by cardiac dysfunction. These results suggest that NO plays a role in cerebral vasodilation during hypoxia in the awake animal.
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D003326:Coronary Circulation / Q000187:drug effects*; D004285:Dogs; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D006863:Hydrogen-Ion Concentration; D000860:Hypoxia / Q000503:physiopathology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D012039:Regional Blood Flow / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects; D014851:Wakefulness
D004791:Enzyme Inhibitors; D001120:Arginine; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester