|Stonehouse, A - AMYLIN PHARMACEUTICALS|
|Guss, S - AMYLIN PHARMACEUTICALS|
|Landry, C - AMYLIN PHARMACEUTICALS|
|Parkes, D - AMYLIN PHARMACEUTICALS|
Submitted to: Metabolic Syndrome and Disorders
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: January 16, 2009
Publication Date: August 1, 2009
Repository URL: http://www.liebertonline.com/doi/pdf/10.1089/met.2008.0095
Citation: Laugero, K.D., Stonehouse, A.H., Guss, S., Landry, C.V., Parkes, D.G. 2009. EXENATIDE IMPROVES HYPERTENSION IN A RAT MODEL OF THE METABOLIC SYNDROME. Metabolic Syndrome and Disorders. 7(4):327-34, 2009. Interpretive Summary: Exenatide is a peptide that helps with the regulation of glucose metabolism. The actions of this peptide are also associated with weight reduction. Our findings are the first demonstration of a durable anti-hypertensive effect of exenatide in a rat model of the metabolic syndrome.
Technical Abstract: Exenatide is a peptide incretin mimetic that has glucoregulatory actions associated with weight reduction. Previous reports demonstrated acute increases in blood pressure after systemic or intracerebroventricular administration of exenatide or glucagon-like peptide-1 (GLP-1) in rats. However, there are no reported studies testing the chronic effects of these peptides on arterial pressure in the rat. Thus, we examined the response to peripheral exenatide using telemetry in conscious, unrestrained rats under normotensive conditions and in a model of hypertension/metabolic syndrome induced by corticosterone. Rats were implanted with either corticosterone or wax (control) pellets (1 ug/kg/d) or vehicle for 7 days. The 21-day corticosterone treatment produced hypertriglyceridemia, visceral fat deposition, hyperglycemia, insulin resistance, and an elevation of mean arterial blood pressure (MAP) by 14 ± 1 mm Hg. Exenatide significantly reversed corticosterone-induced increases in blood presure and this normalization occurred independently from change in body weight. Additionally, exenatide reduced MAP by 5 ± 3 mm Hg in normotensive control rats. These results are the first demonstration of a durable anti-hypertensive effect of exenatide in a glucocorticoid-induced model of the metabolic syndrome.