Vascular ATP-dependent potassium channels, nitric oxide, and human forearmreactive hyperemia

Vascular ATP-dependent potassium (K-ATP(+)) channels open and contribute to reactive hyperemia (RH) in animals. The contribution of K-ATP(+) channels to ischemic vasolidation during RH and interactions with endothelium-derive d nitric oxide have not been well characterized in human subjects. RH blood flow responses (mL/dL) following 5 minutes of cuff occlusion were measured using strain-gauge plethysmography in 22 normal human subjects age 42 +/- 2 years. Measurements were obtained at baseline and following intra-arteria l administration of the K-ATP(+) channel closer glibenclamide, the nitric o xide synthase inhibitor L-N-monomethyl arginine (L-NMMA), or both drugs sim ultaneously. Glibenclamide (100 mu g/min) did not change basal flow (2.7 +/ - 0.3 to 2.7 +/- 0.3 mL/min/dL), but L-NMMA (8 mu mol/min) and combined gli benclamide and L-NMMA significantly (p < 0.05) decreased basal flow (3.0 +/ - 0.5 to 2.0 +/- 0.2 and 3.3 +/- 0.5 to 2.5 +/- 0.3, respectively). Glibenc lamide significantly (p < 0.01) decreased RH flow (18.2 +/- 1.3 to 14.8 +/- 1.3) and excess flow (5.3 +/- 1.2 to 1.3 +/- 1.3). L-NMMA significantly (p < 0.05) decreased RH flow (21.2 +/- 1.8 to 18.9 +/- 1.9) and tended to dec rease excess flow (6.1 +/- 2.2 to 3.9 +/- 2.5). Combined drug infusion sign ificantly (p < 0.1) decreased RH flow (21.6 +/- 2.2 to 18.0 +/- 2.4) and ex cess flow (6.3 +/- 1.6 to 1.6 +/- 1.6), with reductions in RH and excess fl ow similar to those following glibenclamide infusion alone. We conclude tha t forearm vascular K-ATP(+) channels are closed at baseline. They open and contribute to RH vasodilation. The addition of nitric oxide inhibition to K -ATP(+) channel blockade does not result in additive or synergistic inhibit ion of RH.