The endothellum-derived relaxing factor, probably nitric oxide (NO), is a potent vasodilator that regulates the vascular tone in several vascular beds, inclu the brain. We explored the posibi that NO might be of importance for the increase of cerebral blood flow (CBF) a ited with activity of the well-efined neuronal circuits of the rat cerebellar cortex. Laser-loppler fiownry was used to measure increases of cerebellar blood flow evoked by trains of electrical stimulations of the dorsal surface. (25)(26)(27). Local NO synthesis from pre-and postsynaptic sources might therefore influence the microcirculation during periods of neuronal activation. This idea was tested using a specific, irreversible inhibitor of the constitutive form of NOS, NO-nitro-L-arginine (NOLAG), and specific antagonists of NMDA and non-NMDA receptors. Our study indicates that physiological increases of CBF associated with synaptic activity in neuronal networks are partly dependent on neuronal synthesis of NO.
MATERIALS AND METHODSFifty-three male Wistar rats (300-350 g) were anesthetized with halothane (Vapor; Drliger) (4% induction, 1.5% during surgery, and 0.7% maintenance) in 30%6 02/70%6 N20. Catheters were inserted in a femoral artery and a femoral vein, and the trachea was cannulated. After relaxation with 5-15 mg of suxamethonium i.p., rats were ventilated with a volume respirator and placed in a headholder, and the occipital bone and the dura were removed over the cerebellar cortex. The craniotomy site was continuously superfused with artificial cerebrospinal fluid (CSF) at 37C, aerated with 95% 02/5% CO2 (composition in mM: NaCl, 120.00; KCl, 2.8; NaHCO3, 22.00; CaCl2, 1.45; Na2HPO4, 1.00; MgCl2, 0.876 (OffB). The experimental design is depicted in Fig. 1. tTo whom reprint requests should be addressed at: