Adenosine produces pulmonary vasodilation in the perfused rabbit lung via an adenosine A2 receptor.
Adenosine is a potent pulmonary vasodilator that has been used in therapy for clinical and experimental pulmonary hypertension. To determine the receptor responsible for adenosine-induced pulmonary vasodilation, we studied the relative potency of four adenosine agonists in the isolated buffer-perfused rabbit lung during pulmonary hypertension due to infusion of the thromboxane A2 mimetic U46619. The ED50 values for pulmonary vasodilation were 1.9 x 10(-8) mol/L for 5'-N-ethylcarboxamidoadenosine (NECA), 4.5 x 10(-8) mol/L for 2-phenylaminoadenosine (CV-1808), 2.6 x 10(-6) mol/L for R(-)-N6-(2-phenylisopropyl) adenosine (R-PIA), and 6.5 x 10(-6) mol/L for cyclopentyladenosine, results consistent with an adenosine A2 receptor. Pretreatment with the adenosine A1 receptor antagonist cyclopentyltheophylline did not affect the dose-response curve to NECA, and pretreatment with the adenosine A2 receptor antagonist CGS 15943A increased the ED50 of NECA to 2.7 x 10(-7) mol/L. These results suggest that adenosine produces pulmonary vasodilation via activation of an adenosine A2 receptor.
Pearl
R G
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Department of Anesthesia, Stanford University Medical Center, CA 94305-5117.
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000241:Adenosine / Q000037:antagonists & inhibitors / Q000494:pharmacology* / Q000502:physiology; D000818:Animals; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000503:physiopathology*; D008168:Lung / Q000503:physiopathology; D008297:Male; D010477:Perfusion; D011450:Prostaglandin Endoperoxides, Synthetic; D011651:Pulmonary Artery / Q000187:drug effects* / Q000503:physiopathology; D011817:Rabbits; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects* / Q000502:physiology; D013928:Thromboxane A2 / Q000031:analogs & derivatives; D014662:Vasoconstrictor Agents; D014664:Vasodilation / Q000187:drug effects*
D011450:Prostaglandin Endoperoxides, Synthetic; D018341:Receptors, Adrenergic, alpha-2; D014662:Vasoconstrictor Agents; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000241:Adenosine