Insulin-induced increment of coronary flow reserve is not abolished by dexamethasone in healthy young men

Hyperinsulinemia is a risk factor for coronary artery disease. Previous stu dies have reported that hyperinsulinemia increases cardiac and skeletal mus cle sympathetic nerve activity and skeletal muscle blood flow in normal sub jects. However, little is known about insulin's effects on myocardial blood flow in humans. The purpose of this study was to investigate whether physiological hyperins ulinemia affects myocardial blood flow and flow reserve in healthy subjects . Additionally, the role of the sympathetic nervous system in regulating in sulin's effects on coronary perfusion was tested. We used positron emission tomography and oxygen-15-labeled water to measure myocardial blood flow and coronary flow reserve in 16 healthy nonobese men (age, 34 +/- 4yr; maximal aerobic capacity, 32 +/- 3 mL.g(-1).min(-1); blo od pressure, 118 +/- 10/65 +/- 8 mm Hg) at fasting and during euglycemic hy perinsulinemic clamp (1 mU.kg(-1).min(-1) for 80 min). To study the role of the sympathetic nervous system, each subject was studied twice: once after administration of dexamethasone (dexa+) for 2 days (2 mg per day) and once without previous medication (dexa-). All studied subjects had normal left ventricular mass, function, and findings in stress echocardiography. Resting myocardial blood flow was 0.76 +/- 0.19 mL.g(-1).min(-1), and a sig nificant increase in now was detected after adenosine infusion (140 mu g/ k g min for 5 min iv), both in the basal fasting state (P < 0.001) and during hyperinsulinemia (P < 0.001). However, the flow response to adenosine was significantly higher during hyperinsulinemia, thus leading to a higher hype remic flow (3.38 +/- 0.97 us. 4.28 +/- 1.57 mL.g(-1).min(-1), basal vs. hyp erinsulinemic, P < 0.01) and higher coronary flow reserve (4.6 +/- 1.2 vs. 5.8 +/- 0.9, respectively, P < 0.05). Pretreatment with dexamethasone did n ot significantly change the resting blood flow [0.72 +/- 0.22 us. 0.76 +/- 0.19 mL.g(-1).min(-1), dexa+ us. dexa-,not significant (NS)I, the adenosine stimulated flow (3.56 +/- 1.49 vs. 3.38 +/- 0.97 mL.g(-1).min(-1), respect ively, NS), or the hyperinsulinemic adenosine-stimulated blood flow (4.68 /- 1.74 vs. 4.28 +/- 1.57 mL.g(-1).min(-1), respectively, NS). Coronary flo w reserves in the basal state (5.3 +/- 2.7 vs. 4.6 +/- 1.2 mL.g(-1).min(-1) , dexa+ vs, dexa-, NS) and during hyperinsulinemia (6.8 +/- 2.9 vs. 5.8 +/- 1.9 mL.g(-1).min(-1), respectively, NS) tended to be (but were not;) signi ficantly higher after dexamethasone treatment. These results demonstrate that insulin acts as a vasodilatory hormone also in the coronary vasculature. Because the insulin-induced increment of myoca rdial flow reserve remained unchanged by dexamethasone pretreatment, centra lly mediated sympathetic activation seems not to play a major role in regul ating insulin action on myocardial perfusion in healthy subjects.