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The glucagon‐like peptide‐1 receptor antagonist exendin‐9 elevates blood pressure and worsens renal function in SHR (1136.18)
Author(s) -
Aragao Gabriela,
Shimizu Maria,
Davel Ana,
Seguro Antonio,
McDonough Alicia,
Girardi Adriana
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.1136.18
Subject(s) - medicine , endocrinology , blood pressure , glucagon like peptide 1 receptor , agonist , antagonist , type 2 diabetes , receptor , glucagon like peptide 1 , renal function , diabetes mellitus
Pharmacological administration of glucagon‐like peptide‐1 receptor (GLP‐1R) agonists exert cardiorenal beneficial effects beyond blood glucose lowering in type II diabetes and non‐diabetic patients, including reduction of blood pressure. The present study aimed to test the hypothesis that baseline levels of GLP‐1R signaling play a role on blood pressure regulation in hypertensive rats. To this end, 5‐week‐old SHRs were treated with the GLP‐1R antagonist exendin‐9 (EX‐9; 10 µg/rat/day), the GLP‐1R agonist exendin‐4 (EX‐4; 2.5 µg/rat/day) or saline (control) via osmotic mini‐pumps during 4 weeks. Direct recording of BP at the end of the treatment demonstrated that mean blood pressure (MBP) was elevated by exendin‐9 treatment (182±4 mmHg) and lowered by exendin‐4 treatment (161±4 mmHg) when compared to controls (172±1 mmHg, all P<0.05). Exendin‐9 treated SHR also exhibited significantly elevated proteinuria, renal fibrosis, renal TGF‐beta and angiotensinogen expression and macrophage infiltration versus controls. Conversely, exendin‐4 administration exerted anti‐proteinuric, anti‐fibrotic and anti‐inflammatory effects. These findings support the hypothesis that endogenous GLP‐1 levels exert blood pressure lowering and renoprotective effects in hypertensive rats. Grant Funding Source : Supported by FAPESP and USC.