Abstract
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 containing Arrb1 gene (AAV-Arrb1) into the RVLM of SHRs significantly increased NO production and NO synthase (NOS) activity. Microinjection of the non-selective NOS inhibitor N-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.
Highlights
It is well known that β-arrestin1 is an important modulator of G protein-coupled receptor (GPCR) desensitization and internalization (Nuber et al, 2016)
We further assessed whether the β-arrestin1-induced decrease in blood pressure (BP) and renal sympathetic nerve activity (RSNA) of spontaneously hypertensive rat (SHR) was mediated by Nitric oxide (NO) release in the rostral ventrolateral medulla (RVLM)
This study mainly focused on the relationship between NO signaling and β-arrestin1 in the RVLM
Summary
It is well known that β-arrestin is an important modulator of G protein-coupled receptor (GPCR) desensitization and internalization (Nuber et al, 2016). Increasing evidence has proved β-arrestin1’s versatile protective roles in cardiovascular diseases including cardiac injury and cerebral ischemia by regulating certain cellular signaling pathways (Tang et al, 2015; Chen et al, 2017). In the central nervous system, β-arrestin signaling has been found to be involved in the processes of microglia dynamics regulation and maintaining hippocampal neurogenesis (Tao et al, 2015; Li et al, 2016). Our previous study has demonstrated the protective effect of β-arrestin on cardiovascular activity in the rostral ventrolateral medulla (RVLM) of hypertensive rats. It is well known that the RVLM containing the pre-sympathetic neurons plays a key role in maintaining sympathetic vasomotor tone and blood pressure (BP) (Huber and Schreihofer, 2016). The antihypertensive mechanism of β-arrestin in the RVLM needs to be further determined
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
