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

Departments of ¹Medical Pharmacology and Physiology and ²Internal Medicine, School of Medicine, and ³Center for Diabetes and Cardiovascular Health, University of Missouri, Columbia, Missouri; ⁴Division of Neonatology, Department of Pediatrics, Wake Forest University Health Sciences, Winston-Salem, North Carolina; ⁵Department of Pharmacology, University of Vermont, Burlington, Vermont; and ⁶Cellular 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 Ca²⁺ 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). Ca²⁺ 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, Ca²⁺ 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

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