Impaired dilation of coronary arterioles during increases in myocardial O-2 consumption with hyperglycemia

Previous studies showed that nitric oxide (NO) plays an important role in c oronary arteriolar dilation to increases in myocardial oxygen consumption ( M(V)over dotO(2)). We sought to evaluate coronary microvascular responses t o endothelium-dependent and to endothelium-independent vasodilators in an i n vivo model. Microvascular diameters were measured using intravital micros copy in 10 normal (N) and 9 hyperglycemic (HG; 1 wk alloxan, 60 mg/kg iv) d ogs during suffusion of acetylcholine (1, 10, and 100 mu M) or nitroprussid e (1, 10, and 100 mu M) to test the effects on endothelium-dependent and -i ndependent dilation. During administration of acetylcholine, coronary arter iolar dilation was impaired in HG, but was normal during administration of nitroprusside. To examine a physiologically important vasomotor response, 1 0 N and 7 HG control, 5 HG and 5 N during superoxide dismutase (SOD), and 5 HG and 4 N after SQ29,548 (SQ; thromboxane A(2)/prostaglandin H-2 receptor antagonist) dogs were studied at three levels of M(V)over dotO(2) : at res t, during dobutamine (DOB; 10 mu g.kg(-1).min(-1) iv), and during DOB with rapid atrial pacing (RAP; 280 +/- 10 beats/min). During dobutamine, coronar y arterioles dilated similarly in all groups, and the increase in M(V)over dotO(2) was similar among the groups. However, during the greater metabolic stimulus (DOB+RAP), coronary arterioles in N dilated (36 +/- 4% change fro m diameter at rest) significantly more than HG (16 +/- 3%, P < 0.05). In HG +SQ and in HG+SOD, coronary arterioles dilated similarly to N, and greater than HG (P, 0.05). M(V)over dotO(2) during DOB+RAP was similar among groups . Normal dogs treated with SOD and SQ29,548 were not different from untreat ed N dogs. Thus, in HG dogs, dilation of coronary arterioles is selectively impaired in response to administration of the endothelium-dependent vasodi lator acetylcholine and during increases in M(V)over dotO(2).