Elevation of D-glucose impairs coronary artery autoregulation after slight reduction of coronary flow.
Diabetes mellitus is thought to increase the susceptibility of tissue to hypoxic injury through D-glucose-induced alterations of intracellular metabolism. Therefore the effects of hyperglycaemia on coronary artery autoregulation under slight reduction of coronary flow were investigated in isolated perfused guinea-pig hearts. Under normal (10 mM) D-glucose concentrations coronary autoregulation was intact in response to a slight reduction of coronary flow (from 6 to 4.5 mL min-1) when L-arginine as a precursor of the endothelium-derived relaxing factor (EDRF/NO) was available and formation of prostaglandines was intact. Under high (44 mM) D-glucose concentrations on the other hand, a sustained vasodilatation dependent on the availability of L-arginine was observed, when formation of prostaglandins was blocked. This effect was partially reduced in the presence of prostaglandin synthesis. Furthermore, the effect of L-arginine under both conditions could be antagonized by the L-arginine-analogue NG-nitro-L-arginine-methyl-ester (100 microM). Our results suggest that hyperglycaemia impairs coronary artery autoregulation by reducing the threshold for hypoxic vasodilatation in an EDRF/NO-dependent manner. Concomitantly a shift from the formation of vasodilatatory to vasoconstrictive prostaglandines was observed. These results might be of particular interest in patients with diabetes mellitus and ischaemic heart disease.
Wascher
T C
TC
Department of Medicine, University of Graz, School of Medicine, Austria.
Bachernegg
M
M
Kickenweiz
E
E
Stark
G
G
Stark
U
U
Toplak
H
H
Graier
W F
WF
Krejs
G J
GJ
D000818:Animals; D003326:Coronary Circulation; D003331:Coronary Vessels / Q000503:physiopathology*; D005260:Female; D006168:Guinea Pigs; D006706:Homeostasis; D006943:Hyperglycemia / Q000503:physiopathology*; D000860:Hypoxia / Q000503:physiopathology; D008297:Male; D009569:Nitric Oxide / Q000502:physiology
D009569:Nitric Oxide