RAPID REVERSAL OF ENDOTHELIN-1-INDUCED CEREBRAL VASOCONSTRICTION BY INTRATHECAL ADMINISTRATION OF NITRIC-OXIDE DONORS

OBJECTIVE: To determine the capability of donors of nitric oxide (NO) (sodium nitroprusside, nitroglycerine) to reverse endothelin-l (ET-l)- induced cerebral vasoconstriction in vivo, when administered through t he cerebrospinal fluid (CSF) to the adventitial side of the constricte d blood vessel. METHODS: The rabbit basilar artery was exposed through a transcervical, transclival approach and subsequently subjected to p harmacological manipulations and direct observation of effects by vide omicroscopy. Specific manipulations were suffusion of ET-1 (100 nmol/L , 1 ml/min) in synthetic CSF (sCSF) to provoke vasoconstriction and th en either suffusion of an NO donor in sCSF (2 mg/ml/min), or sCSF alon e. The second suffusion was always made separately and begun during th e period of stable maximal vasoconstriction, which occurred between 20 and 30 minutes after beginning the first suffusion. Measurements of t he diameter of the artery were made using an inline video caliper. RES ULTS: Sodium nitroprusside and nitroglycerine, both donors of NO, rapi dly and completely reversed ET-l-induced vasoconstriction without caus ing hypotension. The average value for maximal vasoconstriction by ET- 1/sCSF was 50.4% of baseline arterial diameter and occurred between 20 and 30 minutes. The rate of vasodilatory response was 100% of signifi cantly constricted arteries. The response was complete in less than 6 minutes in all preparations, as compared to the 60 minutes required fo r spontaneous relaxation (sCSF suffusion alone). CONCLUSION: NO donors are effective in reversing cerebral vasoconstriction when administere d intrathecally, cause no significant hemodynamic change when so admin istered, and may represent an important therapeutic intervention for c erebral vasospasm.