Effect of theophylline on hypoxic pulmonary vasoconstriction in awake rats

Whether or not theophylline inhibits hypoxic pulmonary vasoconstriction in vivo still remains uncertain. We therefore studied the effect of theophylline on hypoxic pulmonary vasoconstriction in awake rats. Two days before hemodynamic measurement, indwelling catheters were placed. Animals were divided into three groups; Group-H (20 mg/kg of theophylline), Group-L (8 mg/kg of theophylline), Group-S (saline). At the day of hemodynamic measurement, animals breathed 21% and 10% O2 gas. [{Pulmonary vascular resistance (PVR) during 10% O2-PVR during 21% O2}/PVR during 21% O2] x 100 was termed as hypoxic pulmonary vasoconstriction (HPV). The first HPV measurement was followed without drug administration and then the second HPV measurement was performed with theophylline or saline infusion. Post-theophylline HPV was divided by pre-theophylline HPV to normalize individual variation. Ratio of post-theophylline HPV to pre-theophylline HPV was 0.49 +/- 0.10, 0.77 +/- 0.23, 1.06 +/- 0.33 in Group -H, -L, -S, respectively (means +/- S.E.M). Ratio of post-theophylline HPV to pre-theophylline HPV was significantly less in Group-H than in Group-S. This result suggests that theophylline used in the present study (18.6-26.9 micrograms/ml) attenuates hypoxic pulmonary vasoconstriction in the unanesthetized rat.