Adrenergic vasoconstrictor activity in the cerebral circulation after inhibition of nitric oxide synthesis in conscious goats.

The interaction between nitric oxide (NO) and adrenergic activity in the cerebral circulation was studied using conscious goats, where blood flow to one brain hemisphere (cerebral blood flow) was electromagnetically measured, and the effects of phentolamine and hexamethonium on cerebrovascular resistance were evaluated before (control) and after inhibition of NO synthesis with NW-nitro-L-arginine methyl ester (L-NAME). L-NAME (12 goats, 40 mg kg(-1) administered i.v.) reduced cerebral blood flow from 62 +/- 3 to 44 +/- 2 ml min(-1), increased mean systemic arterial pressure from 100 +/- 3 to 126 +/- 4 mm Hg, decreased heart rate from 79 +/- 5 to 50 +/- 4 beats min(-1) and increased cerebrovascular resistance from 1.63 +/- 0.08 to 2.91 +/- 0.016 mm Hg ml(-1)min(-1) (all P < 0.01). These hemodynamic variables normalized 48-72 h after L-NAME administration. Phentolamine (six goats, 1 mg), injected into the cerebral circulation. increased cerebral blood flow without changing systenic arterial pressure, but its cerebrovascular effects were augmented for about 24 h after L-NAME. The decrements in cerebrovascular resistance induced by phentolamine, in mm Hg ml(-1) min(-1), were: under control, 0.42 +/- 0.05; immediately after L-NAME, 1.38 +/- 0.09 (P < 0.01 compared with control); by about 24 h after L-NAME, 0.71 +/- 0.09 (P < 0.05 compared with control); and by about 48 h after L-NAME, 0.40 +/- 0.07 (P > 0.05 compared with control). Hexamethonium (six goats, 0.5-1 mg kg(-1) min(-1) i.v.) decreased mean systemic arterial pressure to about 75 mm Hg and caused tachycardia similarly before and after L-NAME, but the decrements in cerebrovascular resistance were augmented for about 24 h after L-NAME. The decrements in cerebrovascular resistance induced by hexamethonium, in mm Hg ml(-1).min(-1), were: under control. 0.61 +/- 0.09, immediately after L-NAME, 1.33 +/- 0.16 (P < 0.01 compared with control); by about 24 h after L-NAME, 1.18 +/- 0.10 (P < 0.01 compared with control): and by about 48 h after L-NAME, 0.99 +/- 0.10 (P > 0.05 compared with control). Therefore, these results suggest that adrenergic vasoconstrictor tone in cerebral vasculature may be augmented after inhibition of NO synthesis, and that this increment may contribute to the reduction of cerebral blood flow after inhibition of NO formation.