Low-flow vascular remodeling in the metabolic syndrome X.
Peripheral microvascular dysfunction is a common affliction in patients with the metabolic syndrome X. Previous studies have described a number of vascular impairments in vasomotor control in both human patients and animal models of syndrome X, but the net effect of these impairments on microvascular structure has not been examined. The goal of the current study was to test the hypothesis that syndrome X reduces muscle perfusion and induces vascular remodeling. The obese Zucker rat was used as a model of syndrome X, and the microcirculation of the hindlimb and brain were examined. Obese Zucker rats were obese, hyperlipidemic, hyperinsulinemic, and hyperglycemic. Blood flow to the hindlimb was reduced by 59% in obese rats relative to lean rats. Skeletal muscle resistance arteries of the hindlimb microcirculation of obese rats had thinner walls, smaller lumens, and reduced distensibility. Hindlimb microvessels from obese rats also demonstrated reduced expression of vascular smooth muscle cell markers. Each of these traits is consistent with low-flow remodeling. In contrast, the cerebral microcirculation, where flow is vigorously autoregulated, showed no vascular remodeling nor were there changes in microvascular smooth muscle marker expression. Neither physical activity nor muscle mass were significantly different between lean and obese rats. Taken together, these findings suggest that syndrome X, by reducing hindlimb blood flow, induces a marked remodeling of microcirculation to favor smaller, less distensible vessels. This remodeling may result in an architectural limitation of maximum perfusion capacity and may be an important maladaption in the progression of peripheral microvascular disease.
Stepp
David W
DW
Vascular Biology Center, Medical College of Georgia, 1459 Laney Walker Blvd., Augusta, GA 30912, USA. dstepp@mail.mcg.edu
Pollock
David M
DM
Frisbee
Jefferson C
JC
D000818:Animals; D001158:Arteries / Q000473:pathology / Q000503:physiopathology; D002454:Cell Differentiation; D002560:Cerebrovascular Circulation / Q000502:physiology*; D003187:Compliance; D006614:Hindlimb / Q000098:blood supply; D008297:Male; D024821:Metabolic Syndrome / Q000473:pathology / Q000503:physiopathology*; D008955:Models, Cardiovascular; D009131:Muscle, Smooth, Vascular / Q000473:pathology / Q000502:physiology; D016491:Peripheral Vascular Diseases / Q000473:pathology / Q000503:physiopathology*; D051381:Rats; D011924:Rats, Zucker; D014655:Vascular Resistance / Q000502:physiology