Neuropeptide Y: vasoconstrictor effects and possible role in cerebral vasospasm after experimental subarachnoid hemorrhage

The possible role of neuropeptide Y (NPY) as a vasoconstrictor substance contributing to the development of cerebral vasospasm after experimental subarachnoid hemorrhage was studied. Autologous blood was injected into the cisterna magna of control rabbits and rabbits that had received bilateral superior cervical ganglionectomy 2 days before blood injection. The days after blood injection the concentration of NPY in cerebrospinal fluid (CSF) was 5971 ± 551pg/ml while CSF from control animals contained992 ± 162pg/ml of NPY. The effects of porcine NPY on norepinephrine-induced contraction of rabbit cerebral arteries were also studied in vitro. NPY (1.2 nM) caused a 3-fold potentiation of norepinephrine-induced contraction of cerebral arteries. CSF from control rabbits diluted by 50% with Krebs solution had no significant effect on norepinephrine-induced contraction of cerebral arteries when compared to responses in Krebs solution only; however, diluted CSF from denervated blood-injected rabbits potentiated norepinephrine-induced contraction by 2.6-fold. Antiserum containing NPY specific antibodies was used to immunoprecipitate the peptide from CSF taken from denervated blood-injected rabbits. CSF treated with this antiserum contained less than 40 pg/ml of NPY and had no effect on norepinephrine-induced contraction of cerebral arteries. These results show that the concentration of NPY in CSF of rabbits is elevated after experimetal subarachnoid hemorrhage. In addition, NPY in CSF can potentiate the vasoconstrictor effect of norepinephrine which may contribute to the development of cerebral vasospasm.