Angiotensin II-induced [3H]adenosine release from in situ rat lung.
The purpose of the present study was to determine whether Ang II releases adenosine from the perfused rat lung. Rat lungs were perfused in situ with a physiological salt solution and were loaded with [3H]adenosine. The release of 3H from the perfused rat lung in response to intra-arterial injections of Ang II and other hormones was quantitated. Studies were conducted in both normal rats and in rats that had been nephrectomized before surgery to avoid exposure of the lungs to high levels of endogenous Ang II. Bolus doses of Ang II (10(-12)-10(-7) mol) increased the efflux of 3H from the lungs. Analysis of this effluent by thin-layer chromatography indicated that most of the Ang II-induced release of 3H was [3H]adenosine. The maximal response was usually obtained with 10(-9) mol, and higher doses (10(-8) and 10(-7) mol) mobilized less [3H]adenosine, which suggested tachyphylaxis. The effect of exogenous Ang II on [3H]adenosine release was greatly enhanced when activation of the endogenous renin-angiotensin system was prevented with prior nephrectomy. Infusion of the Ang II selective antagonist, (1-Sar-8-Ile)-Ang II, blocked Ang II-induced [3H]adenosine release. Neither norepinephrine, bradykinin, nor vasopressin consistently released adenosine. We conclude that (a) Ang II can induce the release of adenosine from the perfused rat lung, (b) this effect is receptor mediated, (c) this response is somewhat selective for Ang II, and (d) exposure to high levels of exogenous or endogenous Ang II causes tachyphylaxis so that Ang II-induced adenosine release is attenuated.
Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232.
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Bottiglieri
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Kost
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Jackson
D000241:Adenosine / Q000378:metabolism*; D000758:Anesthesia; D000804:Angiotensin II / Q000031:analogs & derivatives / Q000494:pharmacology*; D000818:Animals; D002855:Chromatography, Thin Layer; D006973:Hypertension / Q000188:drug therapy / Q000503:physiopathology; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009392:Nephrectomy; D011652:Pulmonary Circulation / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D012083:Renin / Q000097:blood; D012504:Saralasin / Q000494:pharmacology
D000804:Angiotensin II; D012083:Renin; D012504:Saralasin; D000241:Adenosine