EFFECTS OF CHANGES IN EXTRACELLULAR pH (▵ pH) ON ISOLATED, PRESSURIZED NEWBORN RESISTANCE VESSELS

The principal site of increased pulmonary vascular resistance is the precapillary arteriole. We hypothesized that isolated pulmonary resistance vessels (PRV) would mimic the unique response of the intact lung to ▵ pH. PRV from newborn piglets were isolated, cannulated at both ends, pressurized to 15 mm Hg and superfused with buffer equilibrated with room air (RA) and 14%, 5% or 2% CO₂ to achieve a buffer pH of 6.8, 7.4 and 7.7, respectively. Spontaneous responses to ▵ pH were studied in 21 PRV (mean lumen diameter (LD) 206; range 115-300 μm). All vessels constricted to 50 mM KCl (22 ± 13% decrease in LD) and demonstrated intact endothelial-dependent dilation to bradykinin (1 μM). After one hour equilibration in RA/5% CO₂ (pH 7.4), the superfusion gas was changed to RA/14% CO₂ (pH 6.8). Acidosis caused a 9 ± 4.6% decrease in LD, which was immediately reversed by changing to RA/2% CO2 (pH 7.7). Continued exposure to alkalosis caused PRV to dilate 15.2 ± 6.6% to a LD consistently larger than that observed at pH 7.4. We investigated the mechanisms responsible for alkalosis-induced vasodilation. Glibenclamide (0.1μM) prevented the increase in LD upon exposure to pH 7.7. Nitro-L-arginine, indomethacin and charybdotoxin were without effect. We conclude that alkalosis-induced pulmonary vasodilation is mediated at least in part by activation of ATP-sensitive K⁺ channels. Isolated, pressurized PRV can be used as a model to study signaling mechanisms mediating the unique responses of the pulmonary circulation to pH.