Effect of nitric oxide blockade by NG-nitro-L-arginine on cerebral blood flow response to changes in carbon dioxide tension.
The importance of nitric oxide (NO) for CBF variations associated with arterial carbon dioxide changes was investigated in halothane-anesthetized rats by using an inhibitor of nitric oxide synthase, NG-nitro-L-arginine (NOLAG). CBF was measured by intracarotid injection of 133Xe. In normocapnia, intracarotid infusion of 1.5, or 7.5, or 30 mg/kg NOLAG induced a dose-dependent increase of arterial blood pressure and a decrease of normocapnic CBF from 85 +/- 10 to 78 +/- 6, 64 +/- 5, and 52 +/- 5 ml 100 g-1 min-1, respectively. This effect lasted for at least 2 h. Raising PaCO2 from a control level of 40 to 68 mm Hg increased CBF to 230 +/- 27 ml 100 g-1 min-1, corresponding to a percentage CBF response (CO2 reactivity) of 3.7 +/- 0.6%/mm Hg PaCO2 in saline-treated rats. NOLAG attenuated this reactivity by 32, 49, and 51% at the three-dose levels. Hypercapnia combined with angiotensin to raise blood pressure to the same level as the highest dose of NOLAG did not affect the CBF response to hypercapnia. L-Arginine significantly prevented the effect of NOLAG on normocapnic CBF as well as blood pressure and also abolished its inhibitory effect on hypercapnic CBF. D-Arginine had no such effect. Decreasing PaCO2 to 20 mm Hg reduced control CBF to 46 +/- 3 ml 100 g-1 min-1 with no further reduction after NOLAG. Furthermore, NOLAG did not change the percentage CBF response to an extracellular acidosis induced by acetazolamide (50 mg/kg).(ABSTRACT TRUNCATED AT 250 WORDS)
Wang
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Department of Clinical Physiology/Nuclear Medicine, Bispebjerg Hospital, Copenhagen, Denmark.
Paulson
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Lassen
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D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D001812:Blood-Brain Barrier / Q000187:drug effects; D002245:Carbon Dioxide / Q000378:metabolism*; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006935:Hypercapnia / Q000378:metabolism; D016857:Hypocapnia / Q000378:metabolism; D008297:Male; D009569:Nitric Oxide / Q000037:antagonists & inhibitors; D019335:Nitroarginine; D051381:Rats; D017208:Rats, Wistar
D002245:Carbon Dioxide; D019335:Nitroarginine; D009569:Nitric Oxide; D001120:Arginine