THE ROLE OF NITRIC-OXIDE IN THE CEREBROVASCULAR RESPONSE TO HYPERCAPNIA

Laser Doppler flowmetry was used to further investigate the role of ni tric oxide (NO) in CO2-induced cerebrocortical hyperemia in rats. A se cond objective was to elucidate the source(s) of the NO involved in th e response to hypercapnia. We used the L-arginine analogue N-omega-nit ro-L-arginine methyl ester (L-NAME) to inhibit NO synthase (NOS) and 7 -nitroindazole (7-NI) to selectively inhibit brain or nonendothelial N OS. Rats were anesthetized with a single dose of intraperitoneal (IP) pentobarbital (65 mg/kg) for surgery; 60-90 min later they were ventil ated with 1.0% halothane in 30% O-2 for 1 h to achieve a steady state. The animals were assigned to one of five groups. A control group (n = 9) was infused with 1 mt of saline. The second group (n = 10) receive d 20 mg/kg of L-NAME intravenously (IV). A third group (n = 9) also re ceived L-NAME; in addition, cerebrocortical laser Doppler flow (LDF) a nd mean arterial pressure (MAP) were restored to baseline using the NO donor sodium nitroprusside (SNP). In a fourth group (n = 9), MAP was increased to the level usually seen after L-NAME with an infusion of p henylephrine (0.5-5 mu g . kg(-1) . min(-1)). A fifth group (n = 11) r eceived 7-NI at 40 mg/kg IF. The hypercapnic response of LDF was teste d in all groups by adding 5% CO2 to the inspired gas at 30-45 min post treatment; all changes in LDF were significant. In the control group, hypercapnia induced a 70% +/- 24% increase in LDF. In the L-NAME-treat ed group, the response was decreased to 36% +/- 22% at a posttreatment LDF that was 25% +/- 13% lower than the pre-L-NAME level. In the grou p where baseline LDF and MAP were restored with SNP, the CO2 response was 56% +/- 15% (not significant versus control). In the group in whic h MAP was increased with phenylephrine, the response to hyper capnia w as 48% +/- 22% at a posttreatment LDF unchanged from pretreatment. The se data suggest that increased vascular tone or the absence of basal N O after NOS inhibition influenced the vasodilator response to hypercap nia. In the 7-NI-treated group the response to hypercapnia was 38% +/- 3%, significantly attenuated at a posttreatment flow only 14% +/- 7% lower than pre-7-NI. We conclude that 1) endothelial NO does not medi- ate the response to hypercapnia but may have a permissive role in the response and 2) that brain NO may have an important role in the respo nse to hypercapnia.