Pinacidil enhances acidosis- and hyperosmolarity-induced coronary arteriolar dilation. Academic Article uri icon


  • Tissue acidosis and hyperosmolarity are factors which participate in the regulation of coronary blood flow. We have demonstrated that acidosis- and hyperosmolarity-induced coronary arteriolar dilation are mediated by the activation of ATP-sensitive potassium (KATP) channels in vascular smooth muscle and vascular endothelium, respectively. Experimental studies following ischemia have shown that administration of a subthreshold dose of KATP channel opener limits the infarct size. However, the protective mechanism is still unclear. We hypothesized that priming the vessel with the KATP channel opener pinacidil may potentiate acidosis- and hyperosmolarityinduced dilation. To achieve this goal, porcine coronary arterioles were isolated, cannulated, and pressurized to 60 cmH2O intraluminal pressure without flow for in vitro study. Acidosis (pH 7.4-7.0) and hyperosmolarity (290-350 mOsm/L) were produced by incrementally adding HCI (0.05N) and D-glucose (5-40 mM) to the vessel bath, respectively. Under control conditions, all vessels developed spontaneous tone and dilated to HCI and glucose in a dose-dependent manner. Extraluminal incubation of a subthreshold dose (0.3 M) of pinacidil for 20 min enhanced acidosisinduced dilation by 50%. In addition, hyperosmolarity-induced dilation was also enhanced by 30% after intraluminal incubation of the same dose of pinacidil. These results suggest that KATP channel openers may improve the vasodilatory ability of coronary resistance vessels in response to acidosis and hyperosmolarity, conditions which are usually associated with ischemia, hypoxia, or increased metabolic demand of the heart.

published proceedings


author list (cited authors)

  • Ishizaka, H., & Kuo, L.

complete list of authors

  • Ishizaka, H||Kuo, L

publication date

  • December 1996