RESUMEN
The Fawn-Hooded rat (FHR) strain reveals a congenital predisposition to primary (idiopathic) pulmonary hypertension (PPH), and can therefore be regarded as an animal model in which to study possible mechanisms underlying an inherited susceptibility to pulmonary hypertension. Pulmonary hypertension can be induced in FHRs after a short exposure to mild hypoxia, presumably because of an altered peripheral oxygen sensitivity. Given the presence of pulmonary nitrergic neurons in rat lungs, the observed link between airway hypoxia and the expression of pulmonary neuronal nitric oxide synthase (nNOS), and the fact that nNOS appears to be involved in peripheral chemoreceptor sensitivity, we examined the intrinsic pulmonary nitrergic innervation in the FHR. In the present study the number of intrapulmonary nitrergic nerve cell bodies, detected by NADPH diaphorase (NADPHd) histochemistry, was quantified in the FHR and three control rat strains. Compared to the control rat strains, the FHR lungs revealed a highly significantly lower number of intrinsic nitrergic neurons, while no apparent differences were found in the number of enteric nitrergic neurons in the esophagus. In conclusion, the possible links between neuronal NO, hypersensitivity to airway hypoxia, and the development of PPH clearly deserve further investigation.
Asunto(s)
Vías Autónomas/anomalías , Hipertensión Pulmonar/patología , Neuronas Nitrérgicas/patología , Arteria Pulmonar/anomalías , Ratas Mutantes/anomalías , Animales , Vías Autónomas/enzimología , Vías Autónomas/patología , Recuento de Células , Modelos Animales de Enfermedad , Regulación hacia Abajo/fisiología , Femenino , Predisposición Genética a la Enfermedad/genética , Hipertensión Pulmonar/genética , Hipertensión Pulmonar/fisiopatología , Inmunohistoquímica , Masculino , NADPH Deshidrogenasa/metabolismo , Neuronas Nitrérgicas/enzimología , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa/metabolismo , Arteria Pulmonar/inervación , Arteria Pulmonar/patología , Ratas , Ratas Endogámicas F344 , Ratas Sprague-Dawley , Ratas Wistar , Especificidad de la Especie , Vasoconstricción/fisiologíaRESUMEN
Axon navigation depends, in part, on guidance cues emanating from the target. We have investigated the possible role of the target in the pathfinding of visceral motor axons to cranial parasympathetic ganglia. Mice homozygous for a tau-LacZ transgene targeted in the Phox2a locus lack the sphenopalatine ganglion, which is the normal target of visceral motor axons of the facial nerve. We found that in these mutants, facial visceral motor axon pathfinding was disrupted, and some axons were misrouted to an alternative parasympathetic ganglion. Moreover, the absence of correct facial visceral motor pathways was concomitant with defects in the pathfinding of rostrally-projecting sympathetic axons.