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- Title
Augmented Contractile Response of Vascular Smooth Muscle in a Diabetic Mouse Model.
- Authors
Okon, Elena B.; Szado, Tania; Laher, Ismail; McManus, Bruce; Van Breemen, Cornelis
- Abstract
The vasomotor properties of isolated aortae and mesenteric arteries of insulin-resistant ob/ob and 57CBL/6J mice were compared in organ bath studies. Vessels from ob/ob mice were more sensitive to phenylephrine. Pretreatment with L-NAME caused similar leftward shifts of the phenylephrine concentration response curves in diabetic and non-diabetic vessels. The ob/ob aortae contracted in response to phenylephrine with roughly twice the force while they were not stiffer than control aortae. L-NAME caused a greater percentage increase in maximal force in the control than in the ob/ob tissue. Denudation potentiated force in the control aortae, but not in the ob/ob aortae. Endothelium-dependent relaxation in the ob/ob aortae and mesenteric arteries was impaired as manifested by a decreased sensitivity and maximal relaxation to acetylcholine, while the aortic basal eNOS mRNA levels did not differ between the two strains. In addition, ob/ob aortae were less sensitive to the nitric oxide donor sodium nitroprusside. Inhibition of endogenous prostaglandin synthesis with indomethacin (10 μM ) partly normalized the contractile response of the ob/ob aortae and enhanced their endothelium-dependent relaxation. Neither blockade of endothelin-1 receptors (bosentan, 10 μM ) nor PKC inhibition (calphostin, 1 μM ) affected the contractile response to phenylephrine in the mouse aortae of either strain. In conclusion, vascular dysfunction in the aorta and mesenteric artery of ob/ob mice are due to increased smooth muscle contractility and impaired dilation but not to changes in elasticity of the vascular wall. Endothelium-produced prostaglandins contribute to the increased vasoconstriction. Copyright © 2003 S. Karger AG, Basel
- Subjects
SMOOTH muscle; NITRIC oxide; VASOCONSTRICTORS; PROSTAGLANDINS; TYPE 2 diabetes
- Publication
Journal of Vascular Research, 2003, Vol 40, Issue 6, p520
- ISSN
1018-1172
- Publication type
Article
- DOI
10.1159/000075238