RESPONSES OF ISOLATED, PRESSURIZED NEWBORN PULMONARY RESISTANCE VESSELS TO CHANGES IN EXTRACELLULAR pH (æ pH) † 1459

Isolated vessel segments have been useful for studying control of vascular tone. For technical reasons, most studies of pulmonary vascular responses have utilized large conductance vessels. However, the principal site of increased pulmonary vascular resistance is the small precapillary arteriole (<300μm diameter). Indeed, the unique pressor response of the intact pulmonary circulation to hypoxia is observed only in isolated resistance vessels. We have similarly found that large conductance vessels do not demonstrate consistent responses to changes in pH (Δ pH). We hypothesized that isolated, pressurized pulmonary resistance vessels would mimic the unique responses of the intact lung to ▵ pH. Pulmonary resistance vessels(<300 μm) from newborn piglets were isolated, cannulated at both ends, pressurized to 15 mm Hg and superfused with NaHCO₃-containing buffer equilibrated with gas mixtures containing room air (RA) plus 14, 5 or 2% CO₂ to achieve a buffer pH of 6.8, 7.4 or 7.7, respectively. The vessel image was projected on a monitor for continuous measurement of the lumen diameter (LD) with a video dimension analysis system. Spontaneous responses to▵ pH were studied in 9 pulmonary resistance vessels from 5 piglets (mean LD 206; range 115-265 μm). All vessels constricted to 50 mM KCl (21± 13% decrease in LD) and demonstrated intact endothelial-dependent dilation to bradykinin (1 μM). After one hour equilibration with stable LD 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 a 15.2 ± 6.6% dilation to a LD consistently larger than that observed at pH 7.4. We conclude that isolated, pressurized pulmonary resistance vessels can be used as a model to study signaling mechanisms mediating the unique responses of the pulmonary circulation to ▵pH. These findings emphasize the importance of viewing the pulmonary circulation as a non-homogeneous unit and of focusing on small precapillary arterioles in investigations of pulmonary vascular responses to hypoxia and pH. (Supported by March of Dimes #6-FY96-0703)