Crosstalk between cardiomyocyte-rich perivascular tissue and coronary arteries is reduced in the Zucker Diabetic Fatty rat model of type 2 diabetes mellitus

L Bonde; P Shokouh; P B Jeppesen; E Boedtkjer

doi:10.1111/apha.12685

Crosstalk between cardiomyocyte-rich perivascular tissue and coronary arteries is reduced in the Zucker Diabetic Fatty rat model of type 2 diabetes mellitus

Acta Physiol (Oxf). 2017 Jan;219(1):227-238. doi: 10.1111/apha.12685. Epub 2016 Apr 21.

Authors

L Bonde¹, P Shokouh^{2

3}, P B Jeppesen⁴, E Boedtkjer¹

Affiliations

¹ Department of Biomedicine, Aarhus University, Aarhus, Denmark.
² Department of Endocrinology and Diabetes, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
³ The Danish Diabetes Academy, Aarhus, Denmark.
⁴ Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark.

PMID: 27042951
DOI: 10.1111/apha.12685

Abstract

Aim: We tested the hypothesis that crosstalk between cardiomyocyte-rich perivascular tissue (PVT) and coronary arteries is altered in diabetes.

Methods: We studied the vasoactive effects of PVT in arteries from the Zucker Diabetic Fatty (ZDF) rat model of type 2 diabetes, streptozotocin (STZ)-treated Wistar rats with type 1 diabetes, and corresponding - heterozygous Zucker Lean (ZL) or vehicle-treated Wistar - control rats. Vasocontractile and vasorelaxant functions of coronary septal arteries with and without PVT were investigated using wire myography.

Results: After careful removal of PVT, vasoconstriction in response to serotonin and thromboxane analogue U46619 was similar in arteries from ZDF and ZL rats, whereas depolarization-induced vasoconstriction - caused by elevating extracellular [K⁺ ] - was reduced in arteries from ZDF compared to ZL rats. PVT inhibited serotonin-, U46619- and depolarization-induced vasoconstriction in arteries from ZL rats, but this anticontractile influence of PVT was attenuated in arteries from ZDF rats. Methacholine-induced vasorelaxation was smaller in arteries from ZDF than ZL rats both with and without PVT, and the antirelaxant influence of PVT was comparable between arteries from ZDF and ZL rats. We observed no differences in vasoconstriction, vasorelaxation or PVT-dependent vasoactive effects between arteries from STZ- and vehicle-treated Wistar rats.

Conclusion: Anticontractile influences of PVT are attenuated in coronary arteries from ZDF rats but unaffected in arteries from STZ-treated rats. Signs of endothelial dysfunction are evident in coronary septal arteries - with and without PVT - from ZDF rats but not STZ-treated rats. We propose that altered signalling between cardiomyocyte-rich PVT and coronary arteries can contribute to cardiovascular complications in type 2 diabetes mellitus.

Keywords: Zucker Diabetic Fatty rats; coronary artery tone; metabolic autoregulation; perivascular tissue; streptozotocin; ventricular dysfunction.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / pharmacology
Animals
Coronary Vessels / drug effects
Coronary Vessels / metabolism*
Diabetes Mellitus, Type 2 / metabolism*
Endothelium, Vascular / drug effects
Endothelium, Vascular / metabolism*
Male
Myocytes, Cardiac / drug effects
Myocytes, Cardiac / metabolism*
Rats
Rats, Wistar
Rats, Zucker
Serotonin / pharmacology
Vasoconstriction / drug effects
Vasodilation / drug effects

Substances

Serotonin
15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid