Growth restriction induced by chronic prenatal hypoxia affects breathing rhythm and its pontine catecholaminergic modulation.
Résumé
Impaired transplacental supply of oxygen leads to intra uterine growth restriction, one of the most important cause of perinatal mortality and respiratory morbidity. The breathing rhythm depends on the central respiratory network modulated by catecholamines. We investigated the impact of growth restriction, using prenatal hypoxia, on the central respiratory-like rhythm and on its catecholaminergic modulation after birth. At birth the respiratory frequency was increased and confirmed in, en bloc medullary preparations where the frequency of the fourth cervical (C4) ventral root discharge was increased, and in slice preparations containing the prebötzinger complex with an increased inspiratory rhythm. The inhibition of the C4 burst discharge observed in ponto-medullary preparation was stronger in the growth restricted group. These results cannot be directly linked by the tyrosine hydroxylase (TH) activity increase of A1/C1 and A2/C2 cell groups in the medulla since blocking the α-adrenergic receptors 1 and 2 does not abolish the difference between both groups. However in ponto-medullary preparation, the stronger inhibition of C4 burst discharge is probably supported by an increased inhibition of A5, a respiratory rhythm inhibitor pontine group of neurons, displaying an increased TH activity because blocking 2 adrenergic receptors abolished the difference between the two groups. Altogether, these results indicate that growth restriction leads to a perturbation of the breathing frequency, which finds, at least in part, its origin in the modification of the catecholaminergic modulation of the central breathing network.