In patients with acute myocardial infarction (MI) it has been demonstrated that a worsened prognosis is associated with the degree of hyperglycaemia on admission to hospital (1,2). Furthermore, coronary artery reperfusion on balloon angioplasty after MI is often impaired in such hyperglycaemic patients worsening outcome. We have previously demonstrated that glucose activates PKC to suppress hyperpolarising Kv channels in smooth muscle(3). We hypothesise that glucose-induced, PKC-mediated vasoconstriction, coupled to a potentiation of vasoconstrictor activity imparts a marked vasoconstriction in the coronary vessels limiting perfusion of the myocardium. Inhibition of the PKC isoforms activated by hyperglycaemia may be an effective therapeutic target for improving outcome after MI. Wire-myography was used to measure vasoconstriction in porcine coronary arteries sourced from a local abattoir. Arterial rings mounted on a myograph were bathed in a solution containing 5 mM (control), 10, or 20 mM (hyperglycaemic) glucose. All solutions were osmotically balanced to 20 mM with mannitol. Vasoconstrictors were added to the bathing solution as appropriate. Exchanging the control bathing solution (5 mM glucose) for one containing 20 mM glucose caused a marked and sustained vasoconstriction in coronary arterioles (8.2±0.7%***, n=16) which was further enhanced if extracellular potassium was raised to 20 mM (27±4%***, n=18)(Contractions all measured against a 60 mM K+ depolarisation, ***P<0.001, t-test). This was found to be PKC-dependent using the pharmacological PKC classical isoform inhibitor Gö6976 (300 nM) which attenuated the increase on exchange solutions (2±1%, n=12). In 10 and 20 mM glucose there was a marked potentiation of the magnitude of contraction (14±5%, 36±7% and 114±6%*** of 60 mM K+ response in 5, 10 and 20 mM glucose respectively, ***P<0.001, n=<15 for each) and the potency of the thromboxane A2 agonist U46619 (-7.0±0.3, -7.4±0.1 and -8.1±0.3*** EC50 value (Log M) for 5, 10 and 20 mM glucose respectively, n=<15 for each). This enhanced vasoconstriction in 20 mM glucose was reversed by pre-treatment with the classical PKC isoform inhibitor Gö6976 (114±6% and 12±3% in 20 mM glucose with and without Gö6976 respectively, n=6) Our data suggest that there is a significant, and acute, effect of hyperglycaemic concentrations of glucose on coronary artery function. A vasoconstriction in response to an elevated glucose and an enhanced response to U46619 could both lead to hypercontractile arteries therefore exacerbating the deleterious effects of MI. These findings highlight the importance of good glycaemic control and also suggest that classical PKC isoforms may be a beneficial therapeutic target in improving the prognosis after myocardial infarction.