The Role of the Paraventricular-Coerulear Network on the Programming of Hypertension by Prenatal Undernutrition

Abstract

A crucial etiological component in fetal programming is early nutrition. Indeed, early undernutrition may cause a chronic increase in blood pressure and cardiovascular diseases, including stroke and heart failure. In this regard, current evidence has sustained several pathological mechanisms involving changes in central and peripheral targets. In the present review, we summarize the neuroendocrine and neuroplastic modifications that underlie maladaptive mechanisms related to chronic hypertension programming after early undernutrition. First, we analyzed the role of glucocorticoids on the mechanism of long-term programming of hypertension. Secondly, we discussed the pathological plastic changes at the paraventricular nucleus of the hypothalamus that contribute to the development of chronic hypertension in animal models of prenatal undernutrition, dissecting the neural network that reciprocally communicates this nucleus with the locus coeruleus. Finally, we propose an integrated and updated view of the main neuroendocrine and central circuital alterations that support the occurrence of chronic increases of blood pressure in prenatally undernourished animals.

Chemogenetic activation of PVN CRH neurons disrupts the estrous cycle and LH dynamics in female mice

“…It has also been demonstrated that PVN neurons remain active after long-term glucocorticoid negative feedback ( 51 ), and chronic stress may even increase the excitability of PVN CRH neurons via multiple mechanisms ( 52 ). Our mathematical modeling could also be extended to interrogate other physiological phenomena such as the mechanisms by which the PVN CRH neural system underlies the adverse outcomes of nutritional programming on cardiovascular disease ( 53 ). Another important consideration is the fact that drinking water behavior is not constant throughout the day.…”