title: Elevation of D-glucose impairs coronary artery autoregulation after slight reduction of coronary flow.
abstract: 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.
authors.affiliation: Department of Medicine, University of Graz, School of Medicine, Austria.
authors.forename: T C
authors.initials: TC
authors.lastname: Wascher
authors.forename: M
authors.initials: M
authors.lastname: Bachernegg
authors.forename: E
authors.initials: E
authors.lastname: Kickenweiz
authors.forename: G
authors.initials: G
authors.lastname: Stark
authors.forename: U
authors.initials: U
authors.lastname: Stark
authors.forename: H
authors.initials: H
authors.lastname: Toplak
authors.forename: W F
authors.initials: WF
authors.lastname: Graier
authors.forename: G J
authors.initials: GJ
authors.lastname: Krejs
mesh_terms: 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
chemical_list: D009569:Nitric Oxide