Diabetic dyslipidemia and exercise affect coronary tone and differential regulation of conduit and microvessel K+ current

• Published in: American journal of physiology. Heart and circulatory physiology Vol. 288; no. 3; pp. H1233 - H1241
• Main Authors: Mokelke, E. A, Dietz, N. J, Eckman, D. M, Nelson, M. T, Sturek, M
• Format: Journal Article
• Language: English
• Published: United States 01.03.2005
• Subjects: Animals; Calcium Signaling - physiology; Coronary Circulation - physiology; Diabetic Angiopathies - diagnostic imaging; Diabetic Angiopathies - physiopathology; Hyperlipidemias - diagnostic imaging; Hyperlipidemias - physiopathology; Male; Microcirculation - physiology; Patch-Clamp Techniques; Physical Conditioning, Animal - physiology; Potassium - metabolism; Potassium Channels - physiology; Swine; Swine, Miniature; Ultrasonography
• ISSN: 0363-6135; 1522-1539
• DOI: 10.1152/ajpheart.00732.2004

Departments of 1 Medical Pharmacology and Physiology and 2 Internal Medicine, School of Medicine, and 3 Center for Diabetes and Cardiovascular Health, University of Missouri, Columbia, Missouri; 4 Division of Neonatology, Department of Pediatrics, Wake Forest University Health Sciences, Winston-Salem, North Carolina; 5 Department of Pharmacology, University of Vermont, Burlington, Vermont; and 6 Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, Indiana Submitted 21 July 2004 ; accepted in final form 27 October 2004 Spontaneous transient outward K + currents (STOCs) elicited by Ca 2+ sparks and steady-state K + currents modulate vascular reactivity, but effects of artery size, diabetic dyslipidemia, and exercise on these differentially regulated K + currents are unclear. We studied the conduit arteries and microvessels of male Yucatan swine assigned to one of three groups for 20 wk: control (C, n = 7), diabetic dyslipidemic (DD, n = 6), or treadmill-trained DD animals (DDX, n = 7). Circumflex artery blood flow velocity obtained with intracoronary Doppler and lumen diameters obtained by intravascular ultrasound enabled calculation of absolute coronary blood flow (CBF). Ca 2+ sparks were determined in pressurized microvessels, and perforated patch clamp assessed K + current in smooth muscle cells isolated from conduits and microvessels. Baseline CBF in DD was decreased versus C. In pressurized microvessels, Ca 2+ spark activity was significantly lower in DD versus C and DDX ( P < 0.05 vs. DDX). STOCs were pronounced in microvessel ( 35 STOCs/min) in sharp contrast to conduit cells ( 2 STOCs/min). STOCs were decreased by 86% in DD versus C and DDX in microvessels; in contrast, there was no difference in STOCs across groups in conduit cells. Steady-state K + current in microvessels was decreased in DD and DDX versus C; in contrast, steady-state K + current in conduit cells was decreased in DDX versus DD and C. We conclude that steady-state K + current and STOCs are differentially regulated in conduit versus microvessels in health and diabetic dyslipidemia. Exercise prevented diabetic dyslipidemia-induced decreases in baseline CBF, possibly via STOC-regulated basal microvascular tone. Yucatan swine; Doppler flow; intravascular ultrasound; vasoreactivity; spontaneous transient outward K + currents; coronary blood flow Address for reprint requests and other correspondence: M. Sturek, Indiana Univ. School of Medicine, 635 Barnhill Dr., MS 309, Indianapolis, IN 46202-5120 (E-mail msturek{at}iupui.edu )