Skeletal Muscle Microvascular Recruitment by Physiological Hyperinsulinemia Precedes Increases in Total Blood Flow

Skeletal Muscle Microvascular Recruitment by Physiological Hyperinsulinemia Precedes Increases in Total Blood Flow M.A. Vincent 1 , D. Dawson 1 , A.D.H. Clark 2 , J.R. Lindner 1 , S. Rattigan 2 , M.G. Clark 2 and E.J. Barrett 1 1 Department of Internal Medicine, University of Virginia Health Sciences Center, Charlottesville, Virginia 2 Division of Biochemistry, Medical School, University of Tasmania, Hobart, Australia Abstract Supraphysiological doses of insulin enhance total limb blood flow and recruit capillaries in skeletal muscle. Whether these processes change in response to physiological hyperinsulinemia is uncertain. To examine this, we infused either saline ( n = 6) or insulin (euglycemic clamp, 3.0 mU · min −1 · kg −1 , n = 9) into anesthetized rats for 120 min. Femoral artery flow was monitored continuously using a Doppler flow probe, and muscle microvascular recruitment was assessed by metabolism of infused 1-methylxanthine (1-MX) and by contrast-enhanced ultrasound (CEU). Insulin infusion raised plasma insulin concentrations by ∼10-fold. Compared with saline, physiological hyperinsulinemia increased femoral artery flow (1.02 ± 0.10 vs. 0.68 ± 0.09 ml/min; P < 0.05), microvascular recruitment (measured by 1-MX metabolism [6.6 ± 0.5 vs. 4.5 ± 0.48 nmol/min; P < 0.05] as well as by CEU [167.0 ± 39.8 vs. 28.2 ± 13.8%; P < 0.01]), and microvascular flow velocity (β, 0.14 ± 0.02 vs. 0.09 ± 0.02 s −1 ). Subsequently, we studied the time dependency of insulin’s vascular action in a second group ( n = 5) of animals. Using CEU, microvascular volume was measured at 0, 30, and 90 min of insulin infusion. Insulin augmented microvascular perfusion within 30 min (52.8 ± 14.8%), and this persisted at 90 min (64.6 ± 9.9%). Microvascular recruitment occurred without changes to femoral artery flow or β. We conclude that insulin increases tissue perfusion by recruiting microvascular beds, and at physiological concentrations this precedes increases in total muscle blood flow by 60–90 min. Footnotes Address correspondence and reprint requests to Michelle Vincent, University of Virginia Health Sciences Center, Box 801390, Charlottesville VA, 22908. E-mail: mav4x{at}virginia.edu . Received for publication 12 March 2001 and accepted in revised form 18 October 2001. β, microvascular flow velocity; CEU, contrast-enhanced ultrasound; 1-MU, 1-methylurate; MV, microvascular volume; 1-MX, 1-methylxanthine.