Abstract 13078: Central Glucagon-like peptide-1 Receptor Activation Counteracts Hypertension with Suppression of Sympathetic Nerve Activity in Spontaneously Hypertensive Rats
Introduction: Incretin related medicines, such as glucagon-like peptide-1 (GLP-1) receptor agonists, are widely used to treat type-2 diabetic patients. Recently, several clinical studies using meta-analysis reported that GLP-1 receptor agonists reduce blood pressure. It has been postulated that GLP-1 reduces blood pressure by acting directly on blood vessels and kidney to promote vasodilation and natriuresis, respectively. In addition to these direct effects on the end effectors, GLP-1 may also regulate blood pressure via the central action. GLP-1 receptors are expressed in the hypothalamus and brain stem regions related to sympathetic and cardiovasucular control including the paraventricular nucleus (PVN), nucleus tractus solitarius (NTS) and rostral ventrolateral medulla (RVLM). The present study explored the central action of GLP-1 on blood pressure and underlying mechanisms.
Methods and Results: Spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats aged 8 weeks were intracerebroventricularly (lateral ventricle) injected with GLP-1 receptor agonist liraglutide (200 pmol) or saline once a day for 2 weeks. In SHR, treatment with liraglutide for 2 weeks, compared with saline, decreased systolic blood pressure measured by tail cuff method (liraglutide, 188±2 mmHg vs. saline, 203±4 mmHg, n=8-9, p<0.01)(Fig A). Intracerebroventricular injection of liraglutide also induced c-Fos expression in the nucleus tractus solitarius (NTS) (47±6 /section vs. 15±3 /section, n=6-7, p<0.01)(Fig B), suppressed urinary norepinephrine excretion (0.58±0.03 μg/day vs. 0.84±0.04 μg/day, n=5, p<0.01)(Fig C), and enhanced endothelial nitric oxide synthase (eNOS) mRNA expression in the renal cortex (eNOS/GAPDH; 0.058±0.004 vs. 0.032±0.005, p<0.05, n=5).
Conclusions: Central GLP-1 receptor activation exerts antihypertensive effect possibly via signaling through NTS to suppress sympathetic nerve activity and induce eNOS in the renal cortex in SHR.
- Diabetes mellitus
- Central nervous system
- Autonomic nervous system
- Blood pressure
Author Disclosures: K. Katsurada: None. Y. Maejima: None. M. Nakata: None. T. Yada: None. K. Kario: None.
- © 2014 by American Heart Association, Inc.