Role of nitric oxide in rat locus coeruleus in hypoxia-induced hyperventilation and hypothermia

Abstract

The locus coeruleus modulates the ventilatory and thermoregulatory response to hypoxia and contains nitric oxide synthase. Therefore, we examined the effects of L-NAME unilaterally microinjected into the locus coeruleus on hypoxic hyperventilation and hypothermia. Ventilation and body temperature were measured before and after microinjection of L-NAME (100 nmol/0.5 microl) into the locus coeruleus, followed by hypoxia. Control rats received microinjection of D-NAME (an inactive enantiomer of L-NAME). Under normoxia, L-NAME treatment did not affect ventilation or body temperature. D-NAME did not affect hypoxia-induced hyperventilation and hypothermia. L-NAME treatment reduced the ventilatory response to hypoxia but did not affect hypoxia-induced hypothermia. These data suggest that nitric oxide in the locus coeruleus is involved in the ventilatory response to hypoxia, exercising an inhibitory modulation on the locus coeruleus neurons, but plays no role in hypoxia-induced hypothermia.

Distribution of NADPH-diaphorase and nitric oxide synthase reactivity in the central nervous system of the goldfish (Carassius auratus)

“…Present results show labeled cells within the locus coeruleus, with a similar morphology to that described with dopamine bhydroxylase immunohistochemistry (Hornby and Piekut, 1990). Nitrergic neurons have not previously been reported within the locus coeruleus in teleosts (Arevalo et al, 1995;Brüning et al, 1995), but they have been found in land vertebrates (Smeets et al, 1997;Fabris et al, 2000;Guo and Longhurst, 2003;Karolewicz et al, 2004;Kodama and Koyama, 2006). Consistent with previous studies in teleosts (Arevalo et al, 1995) and land vertebrates (Munoz et al, 1996;Smeets et al, 1997;Lopez et al, 2005), positive cells were also found within the different subdivisions of the raphe nucleus.…”

Does central nitric oxide chronically modulate the acute hypoxic ventilatory response in conscious rats?

“…In our study, l-NAME and SIN-1 were infused i.c.v. However, as the later two regions are inhibitory nuclei (Fabris et al 2000, Gargaglioni et al 2003, NO effectively attenuates the inhibitory influence of these two nuclei during hypoxia, thereby enhancing the HVR (Fabris et al 2000, Nucci et al 2004. Within the regions of the brainstem associated with ventilatory control, NO can mediate both inhibitory and excitatory components of the HVR (Nucci et al 2004).…”

“…The enzyme NOS has been localized within the nucleus tractus solitarius (NTS) (Ohta et al 1993, Haxhiu et al 1995, the rostral ventrolateral medulla (Shapoval et al 1991, Kishi et al 2002 the nucleus raphe magnus (Leger et al 1998) and implicated within the locus coeruleus (Fabris et al 2000), and acute inhibition of NOS within these regions attenuates the HVR (Haxhiu et al 1995, de Paula & Branco 2003, Nucci et al 2004. The enzyme NOS has been localized within the nucleus tractus solitarius (NTS) (Ohta et al 1993, Haxhiu et al 1995, the rostral ventrolateral medulla (Shapoval et al 1991, Kishi et al 2002 the nucleus raphe magnus (Leger et al 1998) and implicated within the locus coeruleus (Fabris et al 2000), and acute inhibition of NOS within these regions attenuates the HVR (Haxhiu et al 1995, de Paula & Branco 2003, Nucci et al 2004.…”

“…In contrast, NO has been described as an excitatory neuromodulator within the central regions of the brain stem associated with the control of breathing. The enzyme NOS has been localized within the nucleus tractus solitarius (NTS) (Ohta et al 1993, Haxhiu et al 1995, the rostral ventrolateral medulla (Shapoval et al 1991, Kishi et al 2002 the nucleus raphe magnus (Leger et al 1998) and implicated within the locus coeruleus (Fabris et al 2000), and acute inhibition of NOS within these regions attenuates the HVR (Haxhiu et al 1995, de Paula & Branco 2003, Nucci et al 2004. Despite several studies describing the effect of acute NOS inhibition on the HVR, there have not been any reports describing the physiological significance of central NO in the long-term control of breathing, especially with regard to the modulation of HVR.…”

Transient carbon monoxide inhibits the ventilatory responses to hypoxia through peripheral mechanisms in the rat

“…Hypoxia reflexively increases pulmonary ventilation by activating peripheral chemoreceptors, particularly in the carotid bodies (CB) (Taylor et al, 1999). Recent studies using in vitro models have demonstrated that endogenous gaseous compounds, such as CO, play an important role in modulating this hypoxia-induced excitation of chemoreceptors (Fabris et al, 1999(Fabris et al, , 2000Prabhakar, 1995Prabhakar, , 1999Prabhakar, , 2000Prabhakar et al, 1995;Yang et al, 1998). Several lines of evidence have suggested that CO is synthesized endogenously mainly via the catalysis of heme by heme oxygenase (HO) and functions as a chemical messenger (Maines, 1997;Prabhakar et al, 1995).…”