Adenosine produces pulmonary vasoconstriction in sheep. Evidence for thromboxane A2/prostaglandin endoperoxide-receptor activation.
Adenosine, an intermediate product in the metabolism of ATP, is thought to produce vasodilation in all vascular beds with the exception of the kidney. Due to its theoretical potential as a pulmonary vasodilator, we studied the hemodynamic effects of adenosine in the pulmonary vasculature of chronically instrumented awake sheep. Adenosine produced significant pulmonary vasoconstriction instead of the expected vasodilatation. Bolus injections of adenosine into the superior vena cava produced a dose-dependent increase in pulmonary artery pressure that was entirely due to an increase in vascular resistance, since cardiac output decreased slightly. This effect is produced via activation of specific cell surface adenosine receptors, since it was blocked by the adenosine-receptor antagonists theophylline and dipropylsulfophenylxanthine. The cell type involved in adenosine-induced pulmonary vasoconstriction appears to be located within the lung, since vasoconstriction was blunted when adenosine was infused into the left atrium, distal to the lung. However, adenosine does not directly vasoconstrict the pulmonary vasculature, because its effect could be completely abolished by cyclooxygenase inhibition with either indomethacin or ibuprofen and by a thromboxane A2/prostaglandin endoperoxide-receptor antagonist (SQ 29,548). Adenosine-induced vasoconstriction was also greatly reduced after inhibition of thromboxane synthesis. Thus, adenosine produced pulmonary vasoconstriction through generation of a thromboxane/endoperoxide product. Whether endogenous adenosine is involved in the generation of pulmonary vasoconstriction seen in pathophysiological states remains to be determined. To our knowledge, this is the first clear evidence for adenosine-induced vasoconstriction outside the kidney and for an interaction between adenosine and eicosanoid mechanisms.
Biaggioni
I
I
Division of Clinical Pharmacology, Vanderbilt University, Nashville, TN 37232.
King
L S
LS
Enayat
N
N
Robertson
D
D
Newman
J H
JH
D000241:Adenosine / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D007052:Ibuprofen / Q000494:pharmacology; D008168:Lung / Q000502:physiology*; D011449:Prostaglandin Endoperoxides / Q000502:physiology*; D011652:Pulmonary Circulation / Q000187:drug effects*; D011983:Receptors, Purinergic / Q000187:drug effects / Q000502:physiology*; D012756:Sheep; D013806:Theophylline / Q000494:pharmacology; D013928:Thromboxane A2 / Q000502:physiology*; D013929:Thromboxane B2 / Q000097:blood; D013997:Time Factors; D014661:Vasoconstriction / Q000187:drug effects*
D011449:Prostaglandin Endoperoxides; D011983:Receptors, Purinergic; D013929:Thromboxane B2; D013928:Thromboxane A2; D013806:Theophylline; D000241:Adenosine; D007052:Ibuprofen