On the mechanisms of adenosine induced pulmonary vasoconstriction in rats.

Abstract

The effect of adenosine on pulmonary vessels was studied in isolated perfused rat lungs. Drugs were administered intra-arterially in a fixed volume of 0.1 ml Krebs solution as bolus injections. Adenosine responses were obtained before and 10 min after drug injections. When applied in logarithmically increasing doses (1-100 micrograms/ml), adenosine caused dose-dependent increases in pulmonary perfusion pressure (e.g. pulmonary vasoconstriction) which were readily reversible. Challenging adenosine with quinidine, dihydroergocristine and cyproheptadine (2 micrograms/ml each) did not significantly alter adenosine responses. Pretreatment of lungs with 0.5 mM theophylline, 10 micrograms/ml indomethacin, 30 micrograms/ml tebokan (a PAF antagonist) or 1 microgram/ml methylene blue for 10 min, however, antagonized the vasoconstrictor effect of the drug significantly. From these experiments, it was concluded that the mechanisms underlying the pulmonary vasoconstrictor action of adenosine are complex, and that both types of purinoceptors, prostaglandins, PAF and other vascular endothelial hormones might be involved.