Pericardial release of prostacyclin induced by bradykinin and angiotensin II: effects on coronary blood flow in the dog.
Angiotensin II and bradykinin are potent releasers of prostanoids, and it has been suggested that these prostanoids may modulate vascular tone in a number of organs. We previously showed that the pericardium is an important site of prostacyclin biosynthesis, and in this study we have investigated whether or not prostacyclin released into the pericardial fluid influences coronary blood flow. Angiotensin II and bradykinin were infused intra-aortically into anaesthetized dogs, and coronary blood flow in the circumflex artery was measured with electromagnetic probes. Krebs solution irrigating the pericardial surfaces was monitored for prostanoid release using a cascade of bioassay tissues as previously described. Angiotensin II infusions (25 ng/kg/min) increased arterial blood pressure, decreased coronary blood flow, and increased the release of a prostacyclin-like substance into the pericardial irrigating fluid. Inclusion of indomethacin (1 microgram/ml) in the pericardial irrigating fluid abolished angiotensin II-induced release of the prostacyclin-like substance from the heart, did not affect resting coronary flow, but potentiated the coronary vasoconstrictor response to intra-arterial angiotensin II. Bradykinin infusions (0.2 microgram/kg/min) also released the prostacyclin-like substance into the pericardial fluid, and caused a transient decrease in arterial pressure and increase in coronary blood flow. Inclusion of captopril (1 microgram/ml) in the irrigating fluid increased slightly the release of the prostacyclin-like substance, but did not alter the increase in coronary blood flow produced by bradykinin. Moreover, when prostacyclin release was abolished by pericardial indomethacin, the coronary vasodilator response to bradykinin was not altered. A large intravenous dose of indomethacin (5 mg/kg) increased the coronary vasoconstrictor response to angiotensin II, but, again, did not alter the vasodilator response to bradykinin.(ABSTRACT TRUNCATED AT 250 WORDS)
D000287:Administration, Topical; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology*; D002216:Captopril / Q000494:pharmacology; D003326:Coronary Circulation / Q000187:drug effects*; D004285:Dogs; D011464:Epoprostenol / Q000378:metabolism*; D007213:Indomethacin / Q000494:pharmacology; D007261:Infusions, Intra-Arterial; D010490:Pericardial Effusion / Q000378:metabolism*; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
D000804:Angiotensin II; D002216:Captopril; D011464:Epoprostenol; D001920:Bradykinin; D007213:Indomethacin