Cerebral blood flow is reduced by N omega-nitro-L-arginine methyl ester during delayed hypoperfusion in cats.
We tested the hypothesis that decreased tonic release of nitric oxide (NO) or a NO-containing compound, during postischemic delayed hypoperfusion, would result in an impaired response of cerebral blood flow (CBF) to NO synthase inhibition. We measured CBF (microspheres), cerebral oxygen consumption, and physiological variables in 30 halothane-anesthetized cats. In 12 animals, complete cerebral ischemia (verified by midischemic CBF measurement) was produced for 12 min by brachiocephalic and left subclavian artery occlusion with hemorrhagic hypotension (mean arterial blood pressure = 40 mmHg). Steady-state hypoperfusion was present by 120 min of reperfusion (30 +/- 4% of baseline). Nonischemic animals (n = 12) were submitted to the same surgical procedures and anesthetic duration. N omega-nitro-L-arginine methyl ester (L-NAME, 10 mg/kg iv) or saline was administered 160 min after baseline measurements, equivalent to 140 min of reperfusion for animals treated with ischemia (n = 6 in each group). Blood pressure was controlled (aortic ligature) so that there was no change following L-NAME administration both in the ischemic and nonischemic groups. L-NAME reduced CBF during reperfusion in ischemic animals (from 37 +/- 2 to 24 +/- 2 ml.min-1 x 100 g-1) and in nonischemic animals (from 122 +/- 15 to 68 +/- 8 ml.min-1 x 100 g-1) with no change in cerebral oxygen consumption. In six additional cats, administration of L-arginine (250 mg/kg iv) reversed the effect of L-NAME. We conclude that tonic NO-mediated cerebral vasodilation occurs following transient global ischemia despite delayed hypoperfusion.
Clavier
N
N
Department of Anesthesiology and Critical Care Medicine, Johns Hopkins Medical Institutions, Baltimore, Maryland 21287-4963.
Kirsch
J R
JR
Hurn
P D
PD
Traystman
R J
RJ
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001921:Brain / Q000378:metabolism; D002545:Brain Ischemia / Q000378:metabolism / Q000503:physiopathology*; D002415:Cats; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D005073:Evoked Potentials, Somatosensory; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors; D010101:Oxygen Consumption / Q000187:drug effects; D010477:Perfusion; D013997:Time Factors; D014655:Vascular Resistance / Q000187:drug effects
D009569:Nitric Oxide; D001120:Arginine; D019331:NG-Nitroarginine Methyl Ester