Adenosine-induced dilation of coronary resistance vessels is impaired in rats with type 2 diabetes mellitus: possible role of ATP-sensitive potassium channels and nitric oxide

Abstract

Objectives: The purpose of this study was to test the hypothesis that adenosine-induced coronary microvascular dilation is blunted in the animals with diabetes mellitus (DM) through the impairment of K_ATP channel function.
Background: Adenosine-induced coronary vasodilation is demonstrated to be mediated by activation of ATP-sensitive potassium (K_ATP) channels and nitric oxide (NO).
Methods: The hearts of Otsuka Long-Evans Tokushima fatty rats (OLETF, type 2 DM rats), and control Long-Evans Tokushima fatty rats (LETO) at the ages of 32 and 8 weeks were perfused using a Langendorff system with constant perfusion pressure (80 mmHg). Changes in coronary flow to adenosine, pinacidil and sodium nitroprusside (SNP) were examined before and after administration of glibenclamide (10⁻⁷ M), or N^G-nitro-L-arginine methyl ester (L-NAME, 10⁻⁴ M).
Results: At the age of 32 weeks, adenosine- and pinacidil-induced increases in coronary flow were blunted in OLETF as compared with those in LETO (both p<0.05). Glibenclamide attenuated adenosine-induced increase in coronary flow in LETO (p<0.05), but not in OLETF. In contrast, L-NAME attenuated adenosine-induced increase in coronary flow in OLETF (p<0.05), but not in LETO. SNP-induced increases in coronary flow in LETO and OLETF were comparable and were not affected by glibenclamide. In 8-week-old OLETF and LETO, no difference was observed in adenosine-, pinacidil- and SNP-induced increases in coronary flow between OLETF and LETO.
Conclusions: In this type 2 DM model, K_ATP channel function in coronary microcirculation is impaired. Adenosine-induced increase in coronary flow is mediated mainly by NO mechanism.