Cerebral Blood Flow during Hypoxemia and Hemodilution in Rabbits: Different Roles for Nitric Oxide?

Hypoxemia and anemia are associated with increased CBF, but the mechanisms that link the changes in Pao2 or arterial O2 content (Cao2) with CBF are unclear. These experiments were intended to examine the contribution of nitric oxide. Cao2 in pentobarbital-anesthetized rabbits was reduced to approximately 6.5 mL O2/dL by hypoxemia (Pao2 approximately 24 to 26 mm Hg) or hemodilution with hetastarch (hematocrit approximately 14% to 15%). Animals with normal Cao2 (approximately 17.5 to 18 mL O2/dL) served as controls. In part I, each animal was given 3, 10, and 30 mg/kg Nω-nitro-l-arginine methyl ester (l-NAME) intravenously (total 43 mg/kg) to inhibit production of nitric oxide. Forebrain CBF was measured with radioactive microspheres approximately 15 to 20 minutes after each dose. Baseline CBF was greater in hypoxemic rabbits (111 ± 31 mL·100 g−1·min−1, mean ± SD) than in hemodiluted (70 ± 22 mL·100 g−1·min−1) or control animals (39 ± 12 mL·100 g−1·min−1). l-NAME (which reduced brain tissue nitric oxide synthase activity by approximately 65%) reduced CBF in hypoxemic animals to 80 ± 23 mL·100 g−1·min−1 ( P < 0.0001), but had no significant effect on CBF in either anemic or control animals. In four additional rabbits, further hemodilution to a Cao2 of approximately 3.5 mL O2/dL increased baseline CBF to 126 ± 21 mL·100 g−1·min−1, but again there was no effect of l-NAME. In part II, animals were anesthetized as above, and a closed cranial window was prepared. The cyclic GMP (cGMP) content of the artificial CSF superfusate was measured under baseline conditions, and then after the reduction of Cao2 to approximately 6.5 mL O2/dL by either hypoxemia or hemodilution. Concentrations of cGMP did not change during either control conditions or after hemodilution. However, cGMP increased significantly with the induction of hypoxemia. The cGMP increase in hypoxemic animals could be blocked with l-NAME. These results suggest that nitric oxide plays some role in hypoxemic vasodilation, but not during hemodilution.