Angiotensin-induced release of a prostacyclin-like substance from the lungs.
Intravenous infusions of angiotensins I and II into anesthetized dogs caused release of a prostacyclin-like substance into arterial blood: prostacyclin (PGI2) was detected by direct bioassay on bovine coronary artery, rat stomach strip, and rat colon, all of which were treated with phenoxybenzamine, propranolol, and Sar1-Ile8-angiotensin II. This effect of angiotensin I, but not of angiotensin II, was abolished by captopril (1 mg/kg, i.v.), and the effect of angiotensin II was abolished by Sar1-Ala8-angiotensin II (0.5 micrograms/kg/min, i.v.). The PGI2-like substance disappeared during incubation of arterial blood for 6 min, and much less appeared in mixed venous blood withdrawn from the right atrium of pulmonary artery, indicating that it originates from the lungs. Neither arterial nor mixed venous blood contained measurable amounts of prostaglandin E2; infusions of noradrenaline did not release the PGI2-like substance. Release of the PGI2-like substance by angiotensin II was reduced after intravenous administration of indomethacin (2, 5, or 10 mg/kg), aspirin (100 mg/kg), aspirin (100 mg/kg), and meclofenamic acid (2 mg/kg), but was not completely eliminated by any of the above inhibitors. In indomethacin-treated dogs the residual relaxation of the bovine coronary artery induced by intravenous angiotensin II was not further reduced by treating the tissues with hyoscine, mepyramine, cimetidine, and methysergide. Either the pulmonary site of PGI2 biosynthesis, which is stimulated by angiotensin, is partly resistant to inhibition by nonsteroidal anti-inflammatory drugs, or the PGI2-like substance is an unknown substance with similar biological properties.
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D002216:Captopril / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors; D004285:Dogs; D004347:Drug Interactions; D011464:Epoprostenol / Q000378:metabolism*; D005260:Female; D007213:Indomethacin / Q000494:pharmacology; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D011453:Prostaglandins / Q000378:metabolism*; D012504:Saralasin / Q000494:pharmacology
D016861:Cyclooxygenase Inhibitors; D011453:Prostaglandins; D000804:Angiotensin II; D002216:Captopril; D011464:Epoprostenol; D012504:Saralasin; D007213:Indomethacin