Paraventricular-coerulear interactions: role in hypertension induced by prenatal undernutrition in the rat

Rats submitted to fetal growth retardation by in utero malnutrition develop hypertension when adult, showing increased hypothalamic mRNA expression for corticotropin-releasing hormone (CRH) and increased central noradrenergic activity. As hypothalamic CRH serves as an excitatory neurotransmitter within the locus coeruleus (LC) and coerulear norepinephrine plays a similar role within the paraventricular nucleus (PVN) of the hypothalamus, we studied, in both normal and prenatally undernourished 40-day-old anesthetized rats, the effects of intra-LC microinjection of CRH and intra-PVN microinjection of the alpha(1)-adrenoceptor antagonist prazosin on multiunit neuronal activity recorded simultaneously from the two nuclei, as well as the effects on systolic pressure. Undernutrition was induced during fetal life by restricting the diet of pregnant mothers to 10 g daily, whereas mothers of control rats received the same diet ad libitum. At day 40 of postnatal life: (i) undernourished rats showed increased neuronal activity in the PVN and LC, as well as increased systolic pressure; (ii) intra-LC CRH stimulated LC and PVN neurons and increased systolic pressure only in normal rats; (iii) intra-PVN prazosin decreased LC and PVN neuronal activity and systolic pressure only in undernourished rats; and (iv) in normal rats, prazosin prevented the stimulatory effect of CRH only in PVN activity; in undernourished rats, prazosin allowed CRH to regain its stimulatory effects. The results point to the existence of an excitatory PVN-LC closed loop, which seems to be hyperactive in prenatally undernourished rats as a consequence of fetal programming; this loop could be responsible, in part, for the hypertension developed by these animals.