Prostacyclin reduces microvascular fluid conductivity in cat skeletal muscle through opening of ATP-dependent potassium channels

Prostacyclin is suggested to reduce microvascular permeability, but the cel lular mechanisms mediating this response in the microvascular endothelial c ells are still unknown. Considering that prostacyclin relaxes vascular smoo th muscle cells via opening of ATP-dependent potassium channels, and openin g of ATP-dependent potassium channels in the endothelial cells is suggested to influence microvascular permeability, this study was designed to test ( 1) if ATP-dependent potassium channels are involved in the regulation of mi crovascular hydraulic permeability, (2) if the permeability-reducing effect : of prostacyclin is mediated through opening of ATP-dependent potassium ch annels, and (3) if cAMP is involved in this process. An autoperfused cat ca lf hindlimb was used as experimental model, and microvascular hydraulic per meability (conductivity) was estimated by a capillary filtration coefficien t (CFC) technique. The potassium channel opener PCO-400 (0.5 mu g . min(-1) per 100 g muscle, intra-arterially), prostacyclin (1 ng . min(-1) per kg b ody weight, intravenously) and the cAMP analogue dibutyryl-cAMP (24 mu g . min(-1) per 100 g muscle, intra-arterially), decreased CFC to 77, 72 and 69 % compared to central, respectively (p < 0.01). The decrease in CFC obtaine d by these substances was completely restituted after the start of a simult aneous infusion of the ATP-dependent potassium channel blocker glibenclamid e (6 mu g . min(-1) per TOO g muscle, intra-arterially; p < 0.01). Infusion of glibenclamide alone increased CFC to 107% of control (p < 0.05). In con clusion, the ATP-dependent potassium channels contribute to the regulation of microvascular hydraulic conductivity, and the prostacyclin permeability- reducing effect may act through this mechanism via increase in intracellula r cAMP. Copyright(C) 1999 S. Karger AG, Basel.