Abstract
Background: 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 limited studies testing the chronic effects of these peptides on arterial pressure and no reports showing the effects of these peptides to reverse hypertension in the context of the metabolic syndrome. Methods: 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, followed 14 days later by the additional implantation of pumps to deliver exenatide (1 μg/kg per day) or vehicle for 7 days. Results: 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 mmHg. Exenatide significantly reversed corticosterone-induced increases in blood pressure and this normalization occurred independently from change in body weight. Additionally, exenatide reduced MAP by 5 ± 3 mmHg in normotensive control rats. Conclusions: These results are the first demonstration of a durable antihypertensive effect of exenatide in a glucocorticoid-induced model of the metabolic syndrome.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 327-333 |
| Number of pages | 7 |
| Journal | Metabolic Syndrome and Related Disorders |
| Volume | 7 |
| Issue number | 4 |
| DOIs | |
| State | Published - Aug 1 2009 |
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ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism
- Internal Medicine
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Exenatide improves hypertension in a rat model of the metabolic syndrome. / Laugero, Kevin D.; Stonehouse, Anthony H.; Guss, Stacy; Landry, Jannine; Vu, Calvin; Parkes, David G.
In: Metabolic Syndrome and Related Disorders, Vol. 7, No. 4, 01.08.2009, p. 327-333.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Exenatide improves hypertension in a rat model of the metabolic syndrome
AU - Laugero, Kevin D.
AU - Stonehouse, Anthony H.
AU - Guss, Stacy
AU - Landry, Jannine
AU - Vu, Calvin
AU - Parkes, David G.
PY - 2009/8/1
Y1 - 2009/8/1
N2 - Background: 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 limited studies testing the chronic effects of these peptides on arterial pressure and no reports showing the effects of these peptides to reverse hypertension in the context of the metabolic syndrome. Methods: 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, followed 14 days later by the additional implantation of pumps to deliver exenatide (1 μg/kg per day) or vehicle for 7 days. Results: 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 mmHg. Exenatide significantly reversed corticosterone-induced increases in blood pressure and this normalization occurred independently from change in body weight. Additionally, exenatide reduced MAP by 5 ± 3 mmHg in normotensive control rats. Conclusions: These results are the first demonstration of a durable antihypertensive effect of exenatide in a glucocorticoid-induced model of the metabolic syndrome.
AB - Background: 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 limited studies testing the chronic effects of these peptides on arterial pressure and no reports showing the effects of these peptides to reverse hypertension in the context of the metabolic syndrome. Methods: 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, followed 14 days later by the additional implantation of pumps to deliver exenatide (1 μg/kg per day) or vehicle for 7 days. Results: 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 mmHg. Exenatide significantly reversed corticosterone-induced increases in blood pressure and this normalization occurred independently from change in body weight. Additionally, exenatide reduced MAP by 5 ± 3 mmHg in normotensive control rats. Conclusions: These results are the first demonstration of a durable antihypertensive effect of exenatide in a glucocorticoid-induced model of the metabolic syndrome.
UR - http://www.scopus.com/inward/record.url?scp=68549090728&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=68549090728&partnerID=8YFLogxK
U2 - 10.1089/met.2008.0095
DO - 10.1089/met.2008.0095
M3 - Article
C2 - 19320558
AN - SCOPUS:68549090728
VL - 7
SP - 327
EP - 333
JO - Metabolic Syndrome and Related Disorders
JF - Metabolic Syndrome and Related Disorders
SN - 1540-4196
IS - 4
ER -