Hypertension in Prenatally Undernourished Young-Adult Rats Is Maintained by Tonic Reciprocal Paraventricular-Coerulear Excitatory Interactions.

Bernardita Cayupe,Patricio Sáez-Briones,Héctor Burgos,Gustavo Puentes,Rafael Barra,Luis Constandil,Carlos Morgan,Luis Valladares,Amparo Castillo,Miguel Ríos,Alejandro Hernández

doi:10.3390/molecules26123568

Abstract

Prenatally malnourished rats develop hypertension in adulthood, in part through increased α1-adrenoceptor-mediated outflow from the paraventricular nucleus (PVN) to the sympathetic system. We studied whether both α1-adrenoceptor-mediated noradrenergic excitatory pathways from the locus coeruleus (LC) to the PVN and their reciprocal excitatory CRFergic connections contribute to prenatal undernutrition-induced hypertension. For that purpose, we microinjected either α1-adrenoceptor or CRH receptor agonists and/or antagonists in the PVN or the LC, respectively. We also determined the α1-adrenoceptor density in whole hypothalamus and the expression levels of α1A-adrenoceptor mRNA in the PVN. The results showed that: (i) agonists microinjection increased systolic blood pressure and heart rate in normotensive eutrophic rats, but not in prenatally malnourished subjects; (ii) antagonists microinjection reduced hypertension and tachycardia in undernourished rats, but not in eutrophic controls; (iii) in undernourished animals, antagonist administration to one nuclei allowed the agonists recover full efficacy in the complementary nucleus, inducing hypertension and tachycardia; (iv) early undernutrition did not modify the number of α1-adrenoceptor binding sites in hypothalamus, but reduced the number of cells expressing α1A-adrenoceptor mRNA in the PVN. These results support the hypothesis that systolic pressure and heart rate are increased by tonic reciprocal paraventricular–coerulear excitatory interactions in prenatally undernourished young-adult rats.

Highlights

Prenatal undernutrition can program various adaptations in humans and experimental animals
The current study addresses the bidirectional contribution of reciprocal excitatory interactions from locus coeruleus (LC) to PVN and from PVN to LC in the production of hypertension in prenatally malnourished adult rats, along with testing whether any type of sensitization occurs in the PVN, the exit point of the circuit
The present results showed that systolic pressure and heart rate, which were found to be increased in the malnourished group, fell rapidly near control values after either intra-PVN administration of the α1 adrenergic receptor antagonist or intra-LC injection of the antagonist for corticotropin-releasing factor (CRF) receptors (α-helical CRF)

Summary

Introduction

Prenatal undernutrition can program various adaptations in humans and experimental animals. These adaptations, in the short-term, may be beneficial for fetal survival under stress conditions. Animals subjected to prenatal malnutrition showed elevated expression levels of hypothalamic corticotropin-releasing factor (CRF) after birth, as well as chronically increased plasma levels of both adrenocorticotropin (ACTH) [4] and corticosterone hormones [5,6]. These data suggest increased activity of the hypothalamus–

Methods

Results

Discussion

Conclusion