Nitric-oxide synthase-containing nerves facilitate adrenergic transmitter release in sheep middle cerebral arteries

Cerebral blood vessels contain both sympathetic and nitric oxide (NO) synth ase (NOS)-containing nerves. NO has been proposed to modulate smooth muscle function and adrenergic nerve activity, and the nature of this modulation is controversial: some data show NO inhibits norepinephrine (NE) release, w hereas others suggest that NO augments release. To test the hypothesis that in cerebral arteries NO released by NOS-containing nerves augments stimula tion-evoked NE release, we used direct measurement of NE and NO release in isolated sheep middle cerebral arteries. The facial artery, which has not b een reported to be innervated with NOS-containing nerves, was used as an ar tery comparison model. HPLC and redox electrochemical detection was used to measure NE, and NO was measured by chemiluminescence. Stimulation-evoked N E release from the middle cerebral artery significantly declined in the pre sence of the NOS inhibitor N-omega-nitro-L-arginine methyl ester (L-NAME). The effect of L-NAME was reversed by the addition of the NO donor S-nitroso -N-acetyl-DL-penicillamine. In contrast, in facial arteries, L-NAME had no effect on stimulation-evoked NE release, whereas S-nitroso-N-acetyl-DL-peni cillamine still significantly elevated NE release. Activation of perivascul ar nerves significantly increased NE release in both the middle cerebral an d facial arteries. However, when NO was measured in the same samples, stimu lation-evoked release of NO was significantly increased compared with basal release only in middle cerebral arteries. These data support the concept t hat cerebral arteries in the sheep contain both adrenergic and NOS-containi ng nerves. Furthermore, this study provides succinct evidence that NO relea sed from NOS nerves augments stimulation-evoked NE release.