NITRO-L-ARGININE ATTENUATES HYPERCAPNIC CEREBROVASODILATION WITHOUT AFFECTING CEREBRAL METABOLISM

We have previously demonstrated that topical cortical application of nitro-L-arginine (L-NA), a potent inhibitor of nitric oxide (NO) synthesis, attenuates resting cerebral blood flow (CBF) and the cerebrovasodilation elicited by hypercapnia. In this study, we sought to determine whether these cerebrovascular effects of L-NA are secondary to a depression in cerebral metabolism. Rats were anesthetized (chloralose, 80 mg/kg) and artificially ventilated. Arterial pressure and blood gases were monitored. The frontal cortex was exposed and superfused with normal Ringer (pH 7.3-7.4; 37 degrees C) or with Ringer containing L- or D-NA. CBF or cerebral glucose utilization (CGU) was measured autoradiographically using the [C-14]iodoantipyrine of 2-[C-14]deoxy-D-glucose method, respectively. Application of normal Ringer did not affect CBF at the site of superfusion (n = 5; P > 0.05, paired t test). Application of L-NA (1 mM; n = 5), but not D-NA (1 mM; n = 6), attenuated resting CBF by 33 +/- 5% (P < 0.05; analysis of variance). During hypercapnia (partial pressure of CO2 = 55-60 mmHg), L-NA attenuated the CBF increase by 78 +/- 6% (n. = 5/group; P < 0:05 from Ringer), whereas D-NA had no effect (P > 0.05). Resting CBF and the CBF response to hypercapnia were largely unaffected in brain regions outside the field of superfusion. In contrast to hypercapnia, L-NA (1 mM) did not attenuate the increases in CBF elicited by topical application of papaverine (10-1,000 mu M; n = 8). L-NA (1 mM) did not influence CGU at the site of superfusion nor in other brain regions (n = 5/group; P > 0.05 from Ringer). Thus L-NA, but not D-NA, reduces resting CBF and attenuates the CBF response to hypercapnia without affecting CGU. The findings indicate that the cerebrovascular actions of NO synthase inhibitors are not secondary to a depression in cerebral metabolism and support the hypothesis that NO is an important factor in cerebrovascular regulation.