Dose-Dependent Vasodilating Effects of Insulin on Adenosine-Stimulated Myocardial Blood Flow

Abstract

In the peripheral vasculature, insulin induces time- and dose-dependent vasodilation. We have recently demonstrated that insulin potentiates adenosine-stimulated myocardial blood flow. However, it is unknown whether insulin’s effects on the coronary vasculature are dose dependent. In this study, we quantitated myocardial blood flow and adenosine-stimulated coronary flow (140 μg · kg⁻¹ · min⁻¹ for 5 min) in 10 healthy men (age, 32 ± 6 years; BMI, 24.1 ± 1.8 kg/m²) using positron emission tomography and ¹⁵O-labeled water. Hyperemic myocardial blood flow was measured in the basal state, during euglycemic physiological hyperinsulinemia (serum insulin ∼65 mU/l) and during supraphysiological hyperinsulinemia (serum insulin ∼460 mU/l). Basal myocardial blood flow was 0.84 ± 0.17 ml · g⁻¹ · min⁻¹. Physiological hyperinsulinemia increased the adenosine-stimulated flow by 20% (from 3.92 ± 1.17 to 4.72 ± 0.96 ml · g^{− 1} · min⁻¹; P < 0.05). Supraphysiological hyperinsulinemia further enhanced the adenosine-stimulated flow by 19% (to 5.61 ± 1.03 ml · g⁻¹ · min⁻¹; P < 0.05). These effects were not explained by changes in systemic hemodynamics, since coronary resistance decreased during each insulin infusion (P < 0.05). In addition, hyperemic myocardial blood flow responses during insulin stimulation were positively correlated with whole-body glucose uptake. The results demonstrate that insulin is able to enhance hyperemic myocardial blood flow in a dose-dependent manner in healthy subjects. These effects might contribute to the known beneficial dose-dependent effects of insulin on myocardial ischemia.