The myogenic response, the inherent ability of blood vessels to rapidly respond to changes in transmural pressure, is involved in local blood flow autoregulation. Animal studies suggest that both acute hyperglycemia and hyperinsulinemia may impair myogenic vasoconstriction. The purpose of this study was to examine the effects of an oral glucose load on brachial mean blood velocity (MBV) during increases in forearm transmural pressure in humans. Eight healthy men and women (38 +/- 5 yr) underwent an oral glucose tolerance test (OGTT). MBV (in cm/s; Doppler ultrasound) responses to a rise in forearm transmural pressure (arm tank suction, -50 mmHg) were studied before and every 30 min for 120 min during the OGTT. Before the start of the OGTT, MBV was lower than baseline values 30 and 60 s after the application of negative pressure. This suggests that myogenic constriction was present. During the OGTT, blood glucose rose from 88 +/- 2 to 120 +/- 6 mg/dl (P < 0.05) and insulin rose from 14 +/- 1 to 101 +/- 32 microU/ml (P < 0.05). Glucose loading attenuated the reduction in MBV with arm suction (Delta-0.73 +/- 0.14 vs. Delta-1.67 +/- 0.43 cm/s and Delta-1.07 +/- 0.14 vs. Delta-2.38 +/- 0.54 cm/s, respectively, during 30 and 60 s of suction postglucose compared with preglucose values; all P < 0.05). We observed no such time effect for myogenic responses during a sham OGTT. In an additional 5 subjects, glucose loading had no effect on brachial diameters with the application of negative pressure. Oral glucose loading leads to attenuated myogenic vasoconstriction in healthy individuals. The role that this diminished postglucose reactivity plays in mediating postprandial hypotension and/or orthostasis needs to be further explored.