Diabetic dyslipidemia and exercise affect coronary tone and differential regulation of conduit and microvessel K+ current.
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 (approximately 35 STOCs/min) in sharp contrast to conduit cells ( approximately 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.
Mokelke
E A
EA
Department of Medical Pharmacology and Physiology, School of Medicine, Center for Diabetes and Cardiovascular Health, University of Missouri, Columbia, Missouri, USA.
Dietz
N J
NJ
Eckman
D M
DM
Nelson
M T
MT
Sturek
M
M
D000818:Animals; D020013:Calcium Signaling / Q000502:physiology; D003326:Coronary Circulation / Q000502:physiology*; D003925:Diabetic Angiopathies / Q000000981:diagnostic imaging / Q000503:physiopathology*; D006949:Hyperlipidemias / Q000000981:diagnostic imaging / Q000503:physiopathology*; D008297:Male; D008833:Microcirculation / Q000502:physiology; D018408:Patch-Clamp Techniques; D010805:Physical Conditioning, Animal / Q000502:physiology*; D011188:Potassium / Q000378:metabolism; D015221:Potassium Channels / Q000502:physiology*; D013552:Swine; D013556:Swine, Miniature; D014463:Ultrasonography
D015221:Potassium Channels; D011188:Potassium