Vascular resistance and K(f) in normal and PMA-injured rabbit lungs: Effects of adenosine

The effects of adenosine (ADO) on pulmonary vascular resistance (PVR) distribution, vascular compliance (C), and permeability were determined in normal and PMA-injured isolated rabbit lungs perfused with a 1:1 mixture of 6% albumin in Krebs-Henseleit buffer and autologous blood. ADO or vehicle was continuously infused into the reservoir at 1, 4, or 5 μmol/min after a 1-μmol bolus of ADO or vehicle. The capillary filtration coefficient (K(f)) and arterial, venous, and double occlusion pressures were measured at baseline and 30 min after phorbol myristate acetate (PMA; 4 x 10^-8 M) or vehicle. Perfusate differential and total leukocyte counts as well as adenine nucleotides, 6-ketoprostaglandin F(1α) (6-keto-PGF(1α)), and thromboxane B₂ (TxB₂) concentrations were determined at each measurement period. ADO was recovered as hypoxanthine and inosine in the perfusate. ADO alone did not alter PVR, C, K(f), or TxB₂ but reduced 6-keto-PGF(1α) levels. PMA induced an increase in K(f) (0.024 ± 0.002 to 0.040 ± 0.006 g · cmH₂O^-1 · min^-1, P < 0.05) that was completely blocked by 4 or 5 μmol/min ADO. PVR increased by 63 ± 11% after PMA, primarily in the arteries and arterial and venous microvessels. The postcapillary resistance increase was blunted by 4 μmol/min ADO; 5 μmol/min ADO prevented the PVR increase in all segments. ADO did not affect the initial adherence of neutrophils in the lung or the PMA-induced 87 ± 2% decrease in circulating leukocytes (>98% lymphocytes) or threefold increase in TxB₂ levels. These results suggest that protection by ADO is not mediated by the altering of cyclooxygenase products or by leukocyte adherence.