We studied the effect of nitro-
L-arginine methyl ester (
L-NAME), a
nitric oxide synthase (NOS) inhibitor, on the increases in cerebral blood flow (CBF) elicited by stepwise elevations in arterial partial pressure of CO2 (PaCO2) from normocapnia up to 204 mmHg. Rats were anesthetized with
halothane and ventilated. CBF was monitored over the parietal cortex using a
laser-Doppler
flowmeter. Increasing levels of
hypercapnia elicited graded elevations in CBF that reached a plateau at PaCO2 = 82 +/- 1 mmHg (CBF +215 +/- 25%; n = 8; P < 0.05, analysis of variance).
L-NAME (40 mg/kg i.v.; n = 8), but not nitro-D-
arginine methyl ester (n = 8), reduced resting CBF (-42 +/- 4%) and attenuated the increase in CBF elicited by
hypercapnia. The attenuation occurred only at PaCO2 40-80 mmHg and was maximal (-75 +/- 8%; P < 0.05) at 54 +/- 2 mmHg. At PaCO2 > or = 100 mmHg,
L-NAME (40-80 mg/kg) did not attenuate the response (P > 0.05). Reduction of resting CBF (-50 +/- 4%; n = 6) by administration of
chloralose (20-40 mg/kg i.v.) did not attenuate the CBF response to
hypercapnia (P > 0.05). We also found that the attenuation by
L-NAME of resting CBF (n = 5) and of the cerebrovasodilation elicited by
hypercapnia (n = 6) has a relatively slow time course, the effects reaching a maximum 45-60 min after
intravenous administration of the
drug. We conclude that
L-NAME does not attenuate the CBF response to CO2 uniformly at all levels of
hypercapnia.(ABSTRACT TRUNCATED AT 250 WORDS)