title: Mechanisms behind the relaxing effect of furosemide on the isolated rabbit ear artery.
abstract: The effect of furosemide on isometric contraction and 86Rb uptake were studied in the isolated rabbit central ear artery (CEA). A concentration-dependent relaxing effect of furosemide (0.06 mM-1.0 mM) was found in vessel segments with intact endothelium. The maximal relaxation was 28.6 +/- 3.9% (10). The effect was not diminished in segments deprived of endothelium, and removal of endothelium itself caused no change of the force development to electrical field stimulation. The relaxing effect was time-dependent and stimulation-dependent and was not significantly affected by membrane depolarization induced by increasing external [K+] from 10 to 120 mM. The 86Rb uptake was inhibited by both furosemide and ouabain (8.0 +/- 0.5(8) and 5.3 +/- 0.5(8) versus 12.8 +/- 0.9(16) nmol (K+).mm-1.(10 min.)-1 in the furosemide (1.0 mM), ouabain (1.0 mM) and control groups, respectively) without interaction between the two drugs. The 86Rb uptake was not further inhibited by increasing the furosemide concentration from 0.12 mM to 1.0 mM. Our results suggest: firstly, the direct relaxing effect of furosemide on isolated vessel segments is endothelium-independent and secondly, the inhibition of the Na(+)-K(+)-Cl- cotransport and a possible consequent hyperpolarization of the membrane is unlikely to be the sole mechanism responsible for the vasorelaxant effect of furosemide. The demonstrated direct effect on vascular tone may be of clinical importance in situations with very high plasma concentrations of the drug or very low concentrations of serum albumin.
authors.affiliation: Institute of Pharmacology, University of Arhus, Denmark.
authors.forename: R
authors.initials: R
authors.lastname: Tian
authors.forename: C
authors.initials: C
authors.lastname: Aalkjaer
authors.forename: F
authors.initials: F
authors.lastname: Andreasen
mesh_terms: D000818:Animals; D001158:Arteries / Q000187:drug effects* / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D004431:Ear, External / Q000098:blood supply; D004558:Electric Stimulation; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D005110:Extracellular Space / Q000378:metabolism; D005665:Furosemide / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects*; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D011188:Potassium / Q000378:metabolism; D011817:Rabbits; D012414:Rubidium Radioisotopes; D012964:Sodium / Q000378:metabolism
chemical_list: D012414:Rubidium Radioisotopes; D005665:Furosemide; D012964:Sodium; D011188:Potassium; D002118:Calcium