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Am J Physiol Heart Circ Physiol (January 14, 2005). doi:10.1152/ajpheart.00987.2004
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Submitted on September 24, 2004
Accepted on January 10, 2005

Coronary Arteriolar Vasconstriction to Angiotensin II is Augmented in the Prediabetic Metabolic Syndrome via Activation of AT1 Receptors

Cuihua Zhang1, Jarrod D Knudson2, Srinath Setty3, Alberto Araiza2, U D Dincer2, Lih Kuo4, and Johnathan D Tune2*

1 Department of Physiology, Louisiana State University Health Sciences Center, New Orleans, LA, USA; Departments of Anesthesiology and Surgery, Louisiana State University Health Sciences Center, New Orleans, LA, USA
2 Department of Physiology, Louisiana State University Health Sciences Center, New Orleans, LA, USA
3 Department of Integrative Physiology, University of North Texas Health Science Center, Fort worth, TX, USA
4 Department of medical Physiology, Cardiovascular Research Institute, College of Medicine, Texas A&M University System Health Science Center, Temple, TX, USA

* To whom correspondence should be addressed. E-mail: jtune{at}lsuhsc.edu.

The metabolic syndrome is associated with activation of the renin-angiotensin system. However, whether the coronary vascular response to angiotensin II (Ang II) is altered under this condition is unknown. Experiments were conducted in control and chronically high fat fed dogs with the prediabetic metabolic syndrome both in vitro (isolated coronary arterioles, 60-110 µm) and in vivo (anesthetized and conscious). We found that plasma renin activity and Ang II levels are elevated in high-fat fed dogs and that this increase in Ang II is associated with a significant increase in Ang II-mediated coronary vasoconstriction in isolated coronary arterioles and in anesthetized open chest dogs. The vasoconstriction to Ang II is abolished by AT1 receptor blockade. In conscious chronically instrumented dogs, AT1 receptor blockade with telmisartan improved the balance between coronary blood flow and myocardial oxygen consumption in the high fat fed dogs but not in normal control dogs; i.e. the relationship between coronary venous PO2 and myocardial oxygen consumption was shifted upward, toward normal control values. Quantitative assessment of coronary arteriolar AT1 and AT2 receptor mRNA levels by real time PCR revealed no significant difference between normal control and high fat fed dogs, however, Western blot analysis showed a significant increase in AT1 receptor protein level with no change in AT2 receptor protein density. These findings indicate that AT1 receptor mediated coronary constriction is augmented in the prediabetic metabolic syndrome and contributes to impaired control of coronary blood flow via increases in circulating Ang II and/or coronary arteriolar AT1 receptor density.




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