Central Glucagon-like Peptide-1 Receptor Signaling via Brainstem Catecholamine Neurons Counteracts Hypertension in Spontaneously Hypertensive Rats

Authors

Kenichi Katsurada, Jichi Medical University School of Medicine
Masanori Nakata, Jichi Medical University School of Medicine
Toshinobu Saito, Jichi Medical University School of Medicine
Boyang Zhang, Jichi Medical University School of Medicine
Yuko Maejima, Fukushima Medical University School of Medicine
Shyam Sundar Nandi, University of Nebraska Medical CenterFollow
Neeru M. Sharma, University of Nebraska Medical CenterFollow
Kaushik K. Patel, University of Nebraska Medical CenterFollow
Kazuomi Kario, Jichi Medical University School of Medicine
Toshihiko Yada, Jichi Medical University School of Medicine

Document Type

Article

Journal Title

Scientific Reports

Publication Date

2019

Volume

9

Abstract

Glucagon-like peptide-1 receptor (GLP-1R) agonists, widely used to treat type 2 diabetes, reduce blood pressure (BP) in hypertensive patients. Whether this action involves central mechanisms is unknown. We here report that repeated lateral ventricular (LV) injection of GLP-1R agonist, liraglutide, once daily for 15 days counteracted the development of hypertension in spontaneously hypertensive rats (SHR). In parallel, it suppressed urinary norepinephrine excretion, and induced c-Fos expressions in the area postrema (AP) and nucleus tractus solitarius (NTS) of brainstem including the NTS neurons immunoreactive to dopamine beta-hydroxylase (DBH). Acute administration of liraglutide into fourth ventricle, the area with easy access to the AP and NTS, transiently decreased BP in SHR and this effect was attenuated after lesion of NTS DBH neurons with anti-DBH conjugated to saporin (anti-DBH-SAP). In anti-DBH-SAP injected SHR, the antihypertensive effect of repeated LV injection of liraglutide for 14 days was also attenuated. These findings demonstrate that the central GLP-1R signaling via NTS DBH neurons counteracts the development of hypertension in SHR, accompanied by attenuated sympathetic nerve activity.

DOI Link

10.1038/s41598-019-49364-x

ISSN

2045-2322

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Recommended Citation

Katsurada, Kenichi; Nakata, Masanori; Saito, Toshinobu; Zhang, Boyang; Maejima, Yuko; Nandi, Shyam Sundar; Sharma, Neeru M.; Patel, Kaushik K.; Kario, Kazuomi; and Yada, Toshihiko, "Central Glucagon-like Peptide-1 Receptor Signaling via Brainstem Catecholamine Neurons Counteracts Hypertension in Spontaneously Hypertensive Rats" (2019). Journal Articles: Cellular & Integrative Physiology. 36.
https://digitalcommons.unmc.edu/com_cell_articles/36