Published online before print January 2, 2007, doi: 10.1161/01.HYP.0000255576.16089.b9
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(Hypertension. 2007;49:365.)
© 2007 American Heart Association, Inc.
Original Articles |
Elevated Blood Pressure in Transgenic Lipoatrophic Mice and Altered Vascular Function
From the Smooth Muscle Research Program and Department of Anesthesia (Y.-J.G., L.D., C.L., L.-Y.S., W.-S.A., R.M.K.W.L.), McMaster University, Hamilton, Ontario, Canada; the Department of Pathology (K.T.), Kinki University School of Medicine, Osaka-Sayama, Osaka, Japan; and the National Cancer Institute (C.V.), National Institutes of Health, Bethesda, Md.
Correspondence to Robert M.K.W. Lee, HSC-2U3, Department of Anaesthesia, McMaster University, 1200 Main St West, Hamilton, Ontario, Canada L8N 3Z5. E-mail rmkwlee{at}mcmaster.ca
The role of perivascular fat in the control of vascular function was studied using lipoatrophic A-ZIP/F1 transgenic mice. Only a small amount of brown fat was found around the aorta but not around mesenteric arteries. Blood pressure of A-ZIP/F1 mice became higher than wild-type (WT) mice from 10 weeks of age. The presence of perivascular fat reduced the contraction of WT aorta to phenylephrine and serotonin, whereas this effect was either absent or less prominent in A-ZIP/F1 aorta. In WT mice, transfer of solution incubated with aorta with fat to aorta with fat removed caused a relaxation response, but not in A-ZIP/F1 mice, indicating the release of a relaxation factor from perivascular fat in WT aorta. This factor was acting through the activation of calcium-dependent potassium channels. Perfusion of phenylephrine to the isolated mesenteric bed caused a higher increase in perfusion pressure in A-ZIP/F1 than in WT mice. Contractile response of aorta to angiotensin II (Ang II) was mediated by Ang II type 1 receptors and was higher in A-ZIP/F1 than in WT mice. Expression of Ang II type 1 receptors but not Ang II type 2 receptors was higher in aorta of A-ZIP/F1 than WT mice. Treatment with an Ang II type 1 receptor antagonist (TCV 116, 10 mg/kg per day) for 2 weeks normalized the blood pressure of A-ZIP/F1 mice. These results suggest that the absence of perivascular fat tissue, which enhances the contractile response of the blood vessels to agonists, and an upregulation of vascular Ang II type 1 receptors in A-ZIP/F1 mice, are some of the mechanisms underlying the blood pressure elevation in these lipoatrophic mice.
Key Words: lipoatrophy • hypertension • vascular fat function • adipose tissue