Furosemide inhibits thromboxane A2-induced contraction in isolated human internal mammary artery and saphenous vein.
Evidence suggests that, in addition to its diuretic property, furosemide also may exert direct vascular effects. Because thromboxane A2 (TXA2) has a role in the control of vascular tone, we investigated the effect of furosemide on the contraction induced by U46619 (a stable TXA2 mimetic) on isolated human internal mammary artery (IMA) and saphenous vein (SV). Concentration-response curves to U46619 were performed in the absence (vehicle) or the presence of furosemide (0.1-1 mM) on rings of IMA and SV. In addition, the relaxant effect of furosemide (0.1 microM-1 mM) also was evaluated on U46619-precontracted IMA and SV. The participation of cyclooxygenase derivatives was studied by pretreatment with indomethacin. Furosemide (0.1-1.0 mM) caused parallel rightward shifts of U46619 concentration-response curves without affecting the maximal responses in both IMA and SV. Treatment with indomethacin (1 microM) modified neither the inhibitory effect of furosemide on U46619-induced contractions, nor the relaxant effect of furosemide on U46619-induced contractions, nor the relaxant effect of furosemide on U46619-precontracted IMA and SV. In conclusion, furosemide at high concentrations inhibited U46619-induced contraction in human isolated IMA and SV and relaxed U46619-precontracted IMA and SV by mechanisms independent of the release of relaxant prostaglandins. These results suggest that blockade of TXA2 receptors by furosemide may contribute to explaining the therapeutic effects of furosemide in the treatment of severe heart failure.
Stanke-Labesque
F
F
Laboratory of Pharmacology, Faculté de Médecine de Grenoble, France. Françoise.Stanke@ujf-grenoble.fr
Cracowski
J L
JL
Bedouch
P
P
Chavanon
O
O
Magne
J L
JL
Bessard
G
G
Devillier
P
P
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D004347:Drug Interactions; D005665:Furosemide / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D008323:Mammary Arteries / Q000187:drug effects* / Q000503:physiopathology; D012501:Saphenous Vein / Q000187:drug effects* / Q000503:physiopathology; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects
D014662:Vasoconstrictor Agents; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D005665:Furosemide