Acute effects of glyburide on the regulation of peripheral blood flow in normal humans

Recent animal studies have demonstrated that selective blockade of ATP-sensitive K+ (KATP) channels of vascular smooth muscle results in a significant increase in peripheral vascular tone. The main aim of this study was to assess whether glyburide, a selective blocker of KATP channels and commonly used antidiabetic agent, influences resting blood flow and reactive hyperemic response of peripheral tissues of normal subjects. Baseline calf blood flow was measured non-invasively in six normal subjects with femoral venous occlusive plethysmography. Calf blood flow was also serially measured every 30-60 s after the release of calf arterial occlusion (10 min duration). Reactive hyperemia was expressed in terms of peak post-occlusive flow, duration of hyperemia and reactive hyperemic volume. In each subject, baseline flow and reactive hyperemia were measured before (control) and every hour for 5 h after the oral ingestion of either 7.5 mg glyburide or a placebo on two separate days. Baseline calf flow declined by 30 and 42% of control values after 1 and 2 h of glyburide intake (P < 0.05) with a return to control values by hours 3, 4 and 5. Peak post-occlusive flow after 1, 2 and 3 h of glyburide ingestion was lower than control values by 22, 30 and 28%, respectively (P < 0.05). The duration of reactive hyperemia after 2 and 3 h of glyburide ingestion was significantly longer than control values (P < 0.05), whereas reactive hyperemic volume remained unaffected by glyburide intake. Placebo elicited no significant changes in baseline flow or reactive hyperemia throughout the 5-h experimental period.(ABSTRACT TRUNCATED AT 250 WORDS)