Effect of Nitric Oxide Blockade by NG-Nitro-l-Arginine on Cerebral Blood Flow Response to Changes in Carbon Dioxide Tension

Abstract

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, N^G-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 100g⁻¹ min⁻¹, respectively. This effect lasted for at least 2 h. Raising P_aco₂ from a control level of 40 to 68 mm Hg increased CBF to 230 ± 27 ml 100g⁻¹ min⁻¹, corresponding to a percentage CBF response (CO₂ reactivity) of 3.7 ± 0.6%/mm Hg P_aco₂ 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 P_aco₂ to 20 mm Hg reduced control CBF to 46 ± 3 ml 100g⁻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). The results suggest that NO or a closely related compound is involved in the regulation of CBF in normocapnia and even more so in hypercapnia.