title: Negative inotropic effects of furosemide in the isolated rabbit heart: a prostaglandin-mediated event.
abstract: Furosemide is an effective diuretic that initiates a rapid diuresis and peripheral vasodilatation through renal adenylate cyclase inhibition and prostaglandin synthesis. Recently, it has been shown to be associated with activation of the neurohumoral vasoconstrictor mechanism and a further compromise of left ventricular function in patients with heart failure. The present study was performed to investigate the direct effects of furosemide on myocardial performance in the isolated perfused rabbit heart. Furosemide (10(-3) M) caused a significant decrease in developed pressure as well as a similar fall in coronary perfusion pressure. Furosemide also decreased myocardial contractility when the coronary perfusion pressure was kept constant. The change in developed pressure but not the decrease in coronary perfusion pressure could be blocked by treatment with indomethacin. Furosemide did not antagonize rabbit cardiac membrane adenylate cyclase. Therefore, furosemide has a direct inhibitory effect on cardiac contractility that is related to prostaglandin synthesis.
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D003326:Coronary Circulation / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism; D003864:Depression, Chemical; D004280:Dobutamine / Q000494:pharmacology; D005665:Furosemide / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism; D011453:Prostaglandins / Q000502:physiology*; D011817:Rabbits
chemical_list: D011453:Prostaglandins; D005576:Colforsin; D004280:Dobutamine; D005665:Furosemide; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D002118:Calcium; D007213:Indomethacin