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

Prenatally malnourished rats develop hypertension in adulthood, in part through increased α<sub>1</sub>-adrenoceptor-mediated outflow from the paraventricular nucleus (PVN) to the sympathetic system. We studied whether both α<sub>1</sub>-adrenoceptor-mediated noradrenergic ex...

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Main Authors: Bernardita Cayupe, Carlos Morgan, Gustavo Puentes, Luis Valladares, Héctor Burgos, Amparo Castillo, Alejandro Hernández, Luis Constandil, Miguel Ríos, Patricio Sáez-Briones, Rafael Barra
Format: Article
Language:English
Published: MDPI AG 2021-06-01
Series:Molecules
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Online Access:https://www.mdpi.com/1420-3049/26/12/3568
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author Bernardita Cayupe
Carlos Morgan
Gustavo Puentes
Luis Valladares
Héctor Burgos
Amparo Castillo
Alejandro Hernández
Luis Constandil
Miguel Ríos
Patricio Sáez-Briones
Rafael Barra
author_facet Bernardita Cayupe
Carlos Morgan
Gustavo Puentes
Luis Valladares
Héctor Burgos
Amparo Castillo
Alejandro Hernández
Luis Constandil
Miguel Ríos
Patricio Sáez-Briones
Rafael Barra
author_sort Bernardita Cayupe
collection DOAJ
description Prenatally malnourished rats develop hypertension in adulthood, in part through increased α<sub>1</sub>-adrenoceptor-mediated outflow from the paraventricular nucleus (PVN) to the sympathetic system. We studied whether both α<sub>1</sub>-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 α<sub>1</sub>-adrenoceptor or CRH receptor agonists and/or antagonists in the PVN or the LC, respectively. We also determined the α<sub>1</sub>-adrenoceptor density in whole hypothalamus and the expression levels of α<sub>1A</sub>-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 α<sub>1</sub>-adrenoceptor binding sites in hypothalamus, but reduced the number of cells expressing α<sub>1A</sub>-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.
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spelling doaj.art-0e12cd82d55f406fb517eabd8edc1e5e2023-11-21T23:41:08ZengMDPI AGMolecules1420-30492021-06-012612356810.3390/molecules26123568Hypertension in Prenatally Undernourished Young-Adult Rats Is Maintained by Tonic Reciprocal Paraventricular–Coerulear Excitatory InteractionsBernardita Cayupe0Carlos Morgan1Gustavo Puentes2Luis Valladares3Héctor Burgos4Amparo Castillo5Alejandro Hernández6Luis Constandil7Miguel Ríos8Patricio Sáez-Briones9Rafael Barra10Centro de Investigación Biomédica y Aplicada (CIBAP), Escuela de Medicina, Facultad de Ciencias Médicas, Universidad de Santiago de Chile (USACH), Santiago 9170020, ChileLaboratorio de Neurofarmacología y Comportamiento, Escuela de Medicina, Facultad de Ciencias Médicas, Universidad de Santiago de Chile, Santiago 9170020, ChileLaboratorio de Neurofarmacología y Comportamiento, Escuela de Medicina, Facultad de Ciencias Médicas, Universidad de Santiago de Chile, Santiago 9170020, ChileLaboratorio de Hormonas y Receptores, Instituto de Nutrición and Tecnología de los Alimentos (INTA), Universidad de Chile, Santiago 7830490, ChileEscuela de Psicología, Facultad de Ciencias, Universidad Mayor, Santiago 7570008, ChileEscuela de Psicología, Facultad de Ciencias Sociales y Comunicaciones, Universidad Santo Tomás, Santiago 8370003, ChileLaboratorio de Neurobiología, Departamento de Biología, Facultad de Química y Biología, Universidad de Santiago de Chile, Santiago 9170020, ChileLaboratorio de Neurobiología, Departamento de Biología, Facultad de Química y Biología, Universidad de Santiago de Chile, Santiago 9170020, ChileLaboratorio de Neurobiología, Departamento de Biología, Facultad de Química y Biología, Universidad de Santiago de Chile, Santiago 9170020, ChileLaboratorio de Neurofarmacología y Comportamiento, Escuela de Medicina, Facultad de Ciencias Médicas, Universidad de Santiago de Chile, Santiago 9170020, ChileCentro de Investigación Biomédica y Aplicada (CIBAP), Escuela de Medicina, Facultad de Ciencias Médicas, Universidad de Santiago de Chile (USACH), Santiago 9170020, ChilePrenatally malnourished rats develop hypertension in adulthood, in part through increased α<sub>1</sub>-adrenoceptor-mediated outflow from the paraventricular nucleus (PVN) to the sympathetic system. We studied whether both α<sub>1</sub>-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 α<sub>1</sub>-adrenoceptor or CRH receptor agonists and/or antagonists in the PVN or the LC, respectively. We also determined the α<sub>1</sub>-adrenoceptor density in whole hypothalamus and the expression levels of α<sub>1A</sub>-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 α<sub>1</sub>-adrenoceptor binding sites in hypothalamus, but reduced the number of cells expressing α<sub>1A</sub>-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.https://www.mdpi.com/1420-3049/26/12/3568hypertensionprenatal undernutritionparaventricular nucleuslocus coeruleusnoradrenalinecorticotropin-releasing factor
spellingShingle Bernardita Cayupe
Carlos Morgan
Gustavo Puentes
Luis Valladares
Héctor Burgos
Amparo Castillo
Alejandro Hernández
Luis Constandil
Miguel Ríos
Patricio Sáez-Briones
Rafael Barra
Hypertension in Prenatally Undernourished Young-Adult Rats Is Maintained by Tonic Reciprocal Paraventricular–Coerulear Excitatory Interactions
Molecules
hypertension
prenatal undernutrition
paraventricular nucleus
locus coeruleus
noradrenaline
corticotropin-releasing factor
title Hypertension in Prenatally Undernourished Young-Adult Rats Is Maintained by Tonic Reciprocal Paraventricular–Coerulear Excitatory Interactions
title_full Hypertension in Prenatally Undernourished Young-Adult Rats Is Maintained by Tonic Reciprocal Paraventricular–Coerulear Excitatory Interactions
title_fullStr Hypertension in Prenatally Undernourished Young-Adult Rats Is Maintained by Tonic Reciprocal Paraventricular–Coerulear Excitatory Interactions
title_full_unstemmed Hypertension in Prenatally Undernourished Young-Adult Rats Is Maintained by Tonic Reciprocal Paraventricular–Coerulear Excitatory Interactions
title_short Hypertension in Prenatally Undernourished Young-Adult Rats Is Maintained by Tonic Reciprocal Paraventricular–Coerulear Excitatory Interactions
title_sort hypertension in prenatally undernourished young adult rats is maintained by tonic reciprocal paraventricular coerulear excitatory interactions
topic hypertension
prenatal undernutrition
paraventricular nucleus
locus coeruleus
noradrenaline
corticotropin-releasing factor
url https://www.mdpi.com/1420-3049/26/12/3568
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