Double blockade of angiotensin II (AT1)-receptors and ACE does not improve weight gain and glucose homeostasis better than single-drug treatments in obese rats
Version of Record online: 23 MAR 2012
© 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society
British Journal of Pharmacology
Special Issue: Themed Section: Cannabinoids in Biology and Medicine, Part II. Guest Editors: Itai Bab and Steve Alexander
Volume 165, Issue 8, pages 2721–2735, April 2012
How to Cite
Miesel, A., Müller-Fielitz, H., Jöhren, O., Vogt, F. M. and Raasch, W. (2012), Double blockade of angiotensin II (AT1)-receptors and ACE does not improve weight gain and glucose homeostasis better than single-drug treatments in obese rats. British Journal of Pharmacology, 165: 2721–2735. doi: 10.1111/j.1476-5381.2011.01726.x
- Issue online: 23 MAR 2012
- Version of Record online: 23 MAR 2012
- Accepted manuscript online: 20 OCT 2011 10:24AM EST
- Received; 26 June 2011; Revised; 30 August 2011; Accepted; 26 September 2011
- metabolic syndrome;
- insulin resistance;
- hypothalamic–pituitary–adrenal axis;
- renin–angiotensin–aldosterone system;
BACKGROUND AND PURPOSE Combination therapies are becoming increasingly important for the treatment of high blood pressure. Little is known about whether double blockade of angiotensin II (AT1) receptors and angiotensin-converting enzyme (ACE) exert synergistic metabolic effects.
EXPERIMENTAL APPROACH Spontaneously hypertensive rats were allowed to choose between palatable chocolate bars and standard chow and were simultaneously treated with the AT1 blocker telmisartan (8 mg·kgbw−1·day−1), the ACE inhibitor ramipril (4 mg·kgbw−1·day−1) or a combination of the two (8 + 4 mg·kgbw−1·day−1) for 12 weeks.
KEY RESULTS Although food-dependent energy intake was increased by telmisartan and telmisartan + ramipril compared with ramipril or controls, body weight gain, abundance of fat and plasma leptin levels were decreased. Increased insulin levels in response to an oral glucose tolerance test were comparably attenuated by telmisartan and telmisartan + ramipril, but not by ramipril. During an insulin tolerance test, glucose utilization was equally as effectively improved by telmisartan and telmisartan + ramipril. In response to a stress test, ACTH, corticosterone and glucose increased in controls. These stress reactions were attenuated by telmisartan and telmisartan + ramipril.
CONCLUSIONS AND IMPLICATIONS The combination of telmisartan + ramipril was no more efficacious in regulating body weight and glucose homeostasis than telmisartan alone. However, telmisartan was more effective than ramipril in improving metabolic parameters and in reducing body weight. The association between the decrease in stress responses and the diminished glucose levels after stress supports our hypothesis that the ability of telmisartan, as an AT1 receptor blocker, to alleviate stress reactions may contribute to its hypoglycaemic actions.