Adrenergic reactivity after inhibition of nitric oxide synthesis in the cerebral circulation of awake goats

Abstract

The interaction between nitric oxide (NO) and adrenergic reactivity in the cerebral circulation was studied using in vivo and in vitro preparations. Blood flow to one brain hemisphere (cerebral blood flow) was electromagnetically measured in conscious goats, and the effects of norepinephrine, tyramine and cervical sympathetic nerve stimulation were recorded before (control) and after inhibition of NO formation with N w-nitro- l-arginine methyl ester ( l-NAME). The responses to norepinephrine, tyramine and electrical field stimulation were also recorded in segments, 4 mm in length, from the goat's middle cerebral artery under control conditions and after l-NAME. In vivo, l-NAME (10 goats, 47 mg kg −1 administered i.v.) reduced resting cerebral blood flow by 37±2%, increased mean systemic arterial pressure by 24±3%, reduced heart rate by 35±2%, and decreased cerebrovascular conductance by 52±2% (all P<0.01). Norepinephrine (0.3–9 μg), tyramine (50–500 μg), and supramaximal electrical sympathetic cervical nerve stimulation (1.5–6 Hz) decreased cerebrovascular conductance, and these decreases were significantly higher after l-NAME than under control conditions, remaining higher for about 48 h after this treatment. Norepinephrine (10 −8–10 −3 M), tyramine (10 −6–10 −3 M) and electrical field stimulation (1.5–6 Hz) contracted isolated cerebral arteries, and the maximal contraction, but not the sensitivity, was significantly higher in the arteries treated than in non-treated with l-NAME (10 −4 M). Therefore, the reactivity of cerebral vasculature to exogenous and endogenous norepinephrine may be increased after inhibition of NO synthesis. This increase might be related, at least in part, to changes at postjunctional level in the adrenergic innervation of the vessel wall, and it might contribute to the observed decreases in resting cerebral blood flow after inhibition of NO synthesis.