ROLE OF NITRIC-OXIDE IN REGULATION OF BRAIN-STEM CIRCULATION DURING HYPOTENSION

We tested the hypothesis that nitric oxide (NO) plays a role in CBF au toregulation in the brain stem during hypotension. In anesthetized rat s, local CBF to the brain stem was determined with laser-Doppler flowm etry, and diameters of the basilar artery and its branches were measur ed through an open cranial window during stepwise hemorrhagic hypotens ion. During topical application of 10(-5) mol/L and 10(-4) mol/L N-ome ga-nitro-L-arginine (L-NNA), a nonselective inhibitor of nitric oxide synthase (NOS), CBF started to decrease at higher steps of mean arteri al blood pressure in proportion to the concentration of L-NNA in stepw ise hypotension (45 to 60 mm Hg in the 10(-5) mol/L and 60 to 75 mm Hg in the 10(-4) mol/L L-NNA group versus 30 to 45 mm Hg in the control group). Dilator response of the basilar artery to severe hypotension w as significantly attenuated by topical application of L-NNA (maxi mum dilatation at 30 mm Hg: 16 +/- 8% in the 10(-5) mol/L and 12 +/- 5% in the 10(-4) mol/L L-NNA group versus 34 +/- 4% in the control group), but that of the branches was similar between the control and L-NNA gro ups. Topical application of 10(-5) mol/L 7-nitro indazole, a selective inhibitor of neuronal NOS, did not affect changes in CBF or vessel di ameter through the entire pressure range. Thus, endothelial but not ne uronal NO seems to take part in the regulation of CBF to the the brain stem during hypotension around the lower limits of CBF autoregulation . The role of NO in mediating dilatation in response to hypotension ap pears to be greater in large arteries than in small ones.