The Release of Nitric Oxide Is Involved in the β-Arrestin1-Induced Antihypertensive Effect in the Rostral Ventrolateral Medulla
| Autor: | Ming-Juan Xu, Lian-Jie Ge, Tan Xing, Sun Jiacen, Wei-Zhong Wang |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Small interfering RNA Cell signaling hypertension ERK1/2 Chemistry Kinase Physiology Rostral ventrolateral medulla 030204 cardiovascular system & hematology Pharmacology Nitric oxide NO 03 medical and health sciences chemistry.chemical_compound 030104 developmental biology 0302 clinical medicine Physiology (medical) RVLM Extracellular QP1-981 β-arrestin1 Receptor Microinjection Original Research |
| Zdroj: | Frontiers in Physiology Frontiers in Physiology, Vol 12 (2021) |
| ISSN: | 1664-042X |
| Popis: | β-Arrestin1 is a multifunctional scaffold protein with the ability to interact with diverse signaling molecules independent of G protein-coupled receptors. We previously reported that overexpression of β-arrestin1 in the rostral ventrolateral medulla (RVLM) decreased blood pressure (BP) and renal sympathetic nerve activity (RSNA) in spontaneously hypertensive rats (SHRs). Nitric oxide (NO) is widely reported to be involved in central cardiovascular regulation. The goal of this study was to investigate whether NO signaling contributes to the β-arrestin1-mediated antihypertensive effect in the RVLM. It was found that bilateral injection of adeno-associated virus containingArrb1gene (AAV-Arrb1) into the RVLM of SHRs significantly increased NO production and NO synthase (NOS) activity. Microinjection of the non-selective NOS inhibitorN-nitro-L-arginine methyl ester (L-NAME; 10 nmol) into the RVLM prevented the β-arrestin1-induced cardiovascular inhibitory effect. Furthermore, β-arrestin1 overexpression in the RVLM significantly upregulated the expression of phosphorylated neuronal NOS (nNOS) by 3.8-fold and extracellular regulated kinase 1/2 (ERK1/2) by 5.6-fold in SHRs. The β-arrestin1-induced decrease in BP and RSNA was significantly abolished by treatment with ERK1/2 small interfering RNA (ERK1/2 siRNA). Moreover, ERK1/2 siRNA attenuated the β-arrestin1-induced NO production, NOS activity, and nNOS phosphorylation in the RVLM. Taken together, these data demonstrate that the antihypertensive effect of β-arrestin1 in the RVLM is mediated by nNOS-derived NO release, which is associated with ERK1/2 activation. |
| Databáze: | OpenAIRE |
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