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Genetic Deletion of ß-Arrestin 2 From the Subfornical Organ and Other Periventricular Nuclei in the Brain Alters Fluid Homeostasis and Blood Pressure.
Mathieu, Natalia M; Tan, Eden E; Reho, John J; Brozoski, Daniel T; Muskus, Patricia C; Lu, Ko-Ting; Wackman, Kelsey K; Grobe, Justin L; Nakagawa, Pablo; Sigmund, Curt D.
Afiliación
  • Mathieu NM; Department of Physiology (N.M.M., J.J.R., D.T.B., P.C.M., K.-T.L., K.K.W., J.L.G., P.N., C.D.S.), Medical College of Wisconsin, Milwaukee.
  • Tan EE; SUPREMES Program, Marquette University and Medical College of Wisconsin, Milwaukee (E.E.T.).
  • Reho JJ; Department of Physiology (N.M.M., J.J.R., D.T.B., P.C.M., K.-T.L., K.K.W., J.L.G., P.N., C.D.S.), Medical College of Wisconsin, Milwaukee.
  • Brozoski DT; Comprehensive Rodent Metabolic Phenotyping Core (J.J.R., J.L.G.), Medical College of Wisconsin, Milwaukee.
  • Muskus PC; Department of Physiology (N.M.M., J.J.R., D.T.B., P.C.M., K.-T.L., K.K.W., J.L.G., P.N., C.D.S.), Medical College of Wisconsin, Milwaukee.
  • Lu KT; Department of Physiology (N.M.M., J.J.R., D.T.B., P.C.M., K.-T.L., K.K.W., J.L.G., P.N., C.D.S.), Medical College of Wisconsin, Milwaukee.
  • Wackman KK; Department of Physiology (N.M.M., J.J.R., D.T.B., P.C.M., K.-T.L., K.K.W., J.L.G., P.N., C.D.S.), Medical College of Wisconsin, Milwaukee.
  • Grobe JL; Department of Physiology (N.M.M., J.J.R., D.T.B., P.C.M., K.-T.L., K.K.W., J.L.G., P.N., C.D.S.), Medical College of Wisconsin, Milwaukee.
  • Nakagawa P; Department of Physiology (N.M.M., J.J.R., D.T.B., P.C.M., K.-T.L., K.K.W., J.L.G., P.N., C.D.S.), Medical College of Wisconsin, Milwaukee.
  • Sigmund CD; Comprehensive Rodent Metabolic Phenotyping Core (J.J.R., J.L.G.), Medical College of Wisconsin, Milwaukee.
Hypertension ; 81(6): 1332-1344, 2024 Jun.
Article en En | MEDLINE | ID: mdl-38629290
ABSTRACT

BACKGROUND:

ANG (angiotensin II) elicits dipsogenic and pressor responses via activation of the canonical Gαq (G-protein component of the AT1R [angiotensin type 1 receptor])-mediated AT1R in the subfornical organ. Recently, we demonstrated that ARRB2 (ß-arrestin 2) global knockout mice exhibit a higher preference for salt and exacerbated pressor response to deoxycorticosterone acetate salt. However, whether ARRB2 within selective neuroanatomical nuclei alters physiological responses to ANG is unknown. Therefore, we hypothesized that ARRB2, specifically in the subfornical organ, counterbalances maladaptive dipsogenic and pressor responses to the canonical AT1R signaling.

METHODS:

Male and female Arrb2FLOX mice received intracerebroventricular injection of either adeno-associated virus (AAV)-Cre-GFP (green fluorescent protein) to induce brain-specific deletion of ARRB2 (Arrb2ICV-Cre). Arrb2FLOX mice receiving ICV-AAV-GFP were used as control (Arrb2ICV-Control). Infection with ICV-AAV-Cre primarily targeted the subfornical organ with few off targets. Fluid intake was evaluated using the 2-bottle choice paradigm with 1 bottle containing water and 1 containing 0.15 mol/L NaCl.

RESULTS:

Arrb2ICV-Cre mice exhibited a greater pressor response to acute ICV-ANG infusion. At baseline conditions, Arrb2ICV-Cre mice exhibited a significant increase in saline intake compared with controls, resulting in a saline preference. Furthermore, when mice were subjected to water-deprived or sodium-depleted conditions, which would naturally increase endogenous ANG levels, Arrb2ICV-Cre mice exhibited elevated saline intake.

CONCLUSIONS:

Overall, these data indicate that ARRB2 in selective cardiovascular nuclei in the brain, including the subfornical organ, counterbalances canonical AT1R responses to both exogenous and endogenous ANG. Stimulation of the AT1R/ARRB axis in the brain may represent a novel strategy to treat hypertension.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Órgano Subfornical / Presión Sanguínea / Arrestina beta 2 / Homeostasis Límite: Animals Idioma: En Revista: Hypertension Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Órgano Subfornical / Presión Sanguínea / Arrestina beta 2 / Homeostasis Límite: Animals Idioma: En Revista: Hypertension Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos