Attenuation of activity-induced increases in cerebellar blood flow in mice lacking neuronal nitric oxide synthase

Abstract

. Attenuation of activity-induced increases in cerebellar blood flow in mice lacking neuronal nitric oxide synthase. Am J Physiol Heart Circ Physiol 285: H298-H304, 2003. First published March 6, 2003 10.1152/ ajpheart.00043.2003.-We used mice deficient in neuronal nitric oxide (NO) synthase (nNOS) to specifically investigate the role of neuronal NO in the increase of cerebellar blood flow (BFcrb) produced by neural activation. Crus II, a region of the cerebellar cortex that receives trigeminal sensory afferents, was activated by low-intensity stimulation of the upper lip (5-25 V, 4-16 Hz) in anesthetized mice. BFcrb was recorded in Crus II by using a laser-Doppler flow probe. In wild-type mice, upper lip stimulation increased BFcrb in the Crus II by 28 Ϯ 3% (25 V, 10 Hz, n ϭ 6). The rise in BFcrb was attenuated by 73 Ϯ 3% in nNOS Ϫ/Ϫ mice (P Ͻ 0.05, n ϭ 6). The increases in BFcrb produced by superfusion of Crus II with glutamate or by systemic administration of harmaline were also attenuated in nNOS Ϫ/Ϫ mice (P Ͻ 0.05). In contrast, the increases in BFcrb produced by topical superfusion of Crus II with acetylcholine or adenosine and the increase in BFcrb produced by hypercapnia were not affected (P Ͼ 0.05). The field potentials evoked in the Crus II by upper lip stimulation did not differ between wild-type and nNOS-null mice. These data provide the first nonpharmacological evidence that nNOS-derived NO is a critical link between glutamatergic synaptic activity and blood flow in the activated cerebellum.

Methylene blue added to a hypertonic–hyperoncotic solution increases short-term survival in experimental cardiac arrest*

“…Induction of regional cerebral hyperemia has been suggested as the mechanism linking regional neuronal activity with regional cerebral blood flow (33). NO, a potent vasodilator released during synaptic activity, has emerged as an important factor in the development of functional hyperemia (33,34).…”

Nitric oxide increases carbon monoxide production by piglet cerebral microvessels

“…In vivo cerebral microvessels are accompanied by astrocytes and neurons, in particular, that also have glutamate receptors, HO-2, and nNOS. In fact, involvement of nNOS in glutamate-induced cerebrovascular dilation in the mouse cerebellum has been demonstrated (45). Furthermore, the inclusion of HO-2 and glutamate receptors in astrocytes and neurons provides the possibility of glutamate-induced stimulation of CO independent of NO in either of these cell types.…”

Cerebral Blood Flow Regulation by Nitric Oxide: Recent Advances

“…Stellate neurons are probably the major source of NO mediating the vascular response. Increased blood flow in the Crus II in response to upper lip stimulation seen in wildtype mice was attenuated in nNOS-null mice; the increase in cerebellar blood flow by superfusion of Crus II with glutamate or by systemic administration of harmaline was also attenuated in nNOS-knockout mice, implying that nNOS-derived NO is a critical link between glutamatergic synaptic activity and blood flow in the activated cerebellum (Yang et al, 2003). Ayajiki et al (2005) provided evidence indicating that NO released from parasympathetic nerves and neuropeptide(s) released antidromically from sensory nerves seem to be responsible for the increase in cerebral blood flow in the rat.…”