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Enhanced contractility in coronary arteries of diabetic pigs is prevented by exercise

Published online by Cambridge University Press:  09 March 2007

EA Mokelke
Affiliation:
Departments of Medical Pharmacology and Physiology, Internal Medicine and the Diabetes and Cardiovascular Biology Program, University of Missouri, Columbia, MO 65212, USA
Q Hu
Affiliation:
Departments of Medical Pharmacology and Physiology, Internal Medicine and the Diabetes and Cardiovascular Biology Program, University of Missouri, Columbia, MO 65212, USA
JR Turk
Affiliation:
Departments of Medical Pharmacology and Physiology, Internal Medicine and the Diabetes and Cardiovascular Biology Program, University of Missouri, Columbia, MO 65212, USA
M Sturek*
Affiliation:
Biomedical Sciences, University of Missouri, Columbia, MO 65212, USA
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Abstract

We hypothesized that hyperlipidaemia, diabetes and diabetic dyslipidaemia increase the contractility of coronary arteries in swine, and that exercise would prevent this enhanced contractility. We further hypothesized that this enhanced contractility is associated with elevated potassium (K+) channel activity, consistent with the idea that certain disease states, as in hypertension, result in a compensatory upregulation in K+ channels. Swine were assigned to one of the following groups: control, standard chow (C; n=6); hyperlipidaemic, high-fat chow (H; n=5); diabetic, standard chow (D; n=7); diabetic, high-fat chow (‘diabetic dyslipidaemic’, DD; n=12); or exercise-trained DD (DDX; n=9). High-fat chow consisted of standard pig chow with added cholesterol (2%) and coconut oil. Endothelium-denuded segments from D, DD and DDX animals showed enhanced contractility to prostaglandin F2α (PGF2α) compared with C, while segments from H, D and DD showed enhanced contractility to endothelin-1 (ET-1) compared with C and DDX (P<0.05). The enhanced contractility was not accompanied by differences in K+ channel contribution to force reduction. There was no effect of the treatments on expression of the endothelin receptor A or endothelin receptor B. A possible mechanism for the enhanced vasoreactivity of coronary arteries of H, D and DD swine is an alteration in the signalling pathways of ET-1- and PGF2α-induced contraction. Exercise prevented the increase in contractility to ET-1, but not to PGF2α, reinforcing the concept of vasoconstrictor specificity.

Type
Research Article
Copyright
Copyright © Cambridge University Press 2004

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