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

E. A. Mokelke, N. J. Dietz, D. M. Eckman, M. T. Nelson, Michael Sturek

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

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.

Original languageEnglish
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume288
Issue number3 57-3
DOIs
StatePublished - Mar 2005

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Dyslipidemias
Microvessels
Dichlorodiphenyl Dichloroethylene
Arteries
Blood Flow Velocity
Smooth Muscle Myocytes
Blood Vessels
Swine
Health

Keywords

  • Coronary blood flow
  • Doppler flow
  • Intravascular ultrasound
  • Spontaneous transient outward K currents
  • Vasoreactivity
  • Yucatan swine

ASJC Scopus subject areas

  • Physiology

Cite this

Diabetic dyslipidemia and exercise affect coronary tone and differential regulation of conduit and microvessel K+ current. / Mokelke, E. A.; Dietz, N. J.; Eckman, D. M.; Nelson, M. T.; Sturek, Michael.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 288, No. 3 57-3, 03.2005.

Research output: Contribution to journalArticle

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abstract = "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.",
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