Coronary arterioles of type 2 diabetic patients exhibit diminished dilation to sudden increases in wall shear stress

Abstract

Percutaneous coronary intervention (PCI) is commonly associated with coronary no‐reflow (CnRF), a poorly understood phenomenon in which myocardial hypoperfusion persists despite re‐opening the occluded coronary artery. Patients with diabetes (DM) are highly susceptible for developing CnRF. We hypothesized that CnRF is due to the disturbed regulation of coronary arteriolar diameter by wall shear stress (WSS) in DM patients. Coronary arterioles (~100 um) were dissected from atrial appendages and diameter changes were measured to low (10 dyne/cm2) and high (50 dyne/cm2) levels of WSS, as evoked by increases in intraluminal flow ‐ simulating arteriolar WSS changes during PCI. In response to increases in WSS, arterioles from nonDM patients developed significant dilation (19±4% and 8±6%). Arterioles from DM subjects did not respond to increases in WSS (3±4% and −4±1%). Inhibition of NO synthesis with L‐NAME attenuated WSS‐induced dilation in nonDM vessels (5%±3%), while no effect was observed in DM arterioles (−2±2%). The NO donor sodium nitroprusside elicited similar dilation in the two groups. As assessed by quantitative RT‐PCR, there was no difference in eNOS expression in arterioles of DM and nonDM patients. Thus, lack of WSS‐induced NO release in vessels of DM patients leads to a diminished coronary dilation, which may contribute to CnRF. (Supported by: NIH HL104126, PO1HL43023, BHF RE/08/004)