Selective pulmonary and venous smooth muscle relaxation by furosemide: a comparison with morphine.
Furosemide and morphine reduce pulmonary edema associated with congestive heart failure. It is uncertain whether furosemide or morphine are direct-acting relaxants of arterial and venous smooth muscle. The authors compared the effect of furosemide and morphine on isolated rings of canine pulmonary artery (PA) and vein (PV) and mesenteric, splenic and anterior tibial arteries and their corresponding veins precontracted with norepinephrine or (15S)-hydroxy-11 alpha, 9 alpha-(epoxymethano)prosta-5Z,13E-dienoic acid. Furosemide (10-300 microM) selectively relaxed veins by an endothelium-independent mechanism, with its greatest efficacy on the PV. Morphine (10-1000 microM) relaxed both arteries and veins. The mechanism of relaxation by furosemide and morphine was examined in the PV and PA. Morphine-induced relaxation of the PV and PA was dependent on prostanoid release from endothelium and smooth muscle because it was attenuated in endothelium-rubbed and ibuprofen-treated PV and PA but not in blood vessels treated with inhibitors of nitric oxide system/cyclic GMP system (I-NG-nitroarginine and methylene blue). Furosemide-mediated relaxation of the PV was refractory to each of these interventions. Similarly, furosemide- and morphine-induced relaxation of the PV were unaffected by 4-aminopyridine, tetraethylammonium, glibenclamide, dendrodotoxin and apamin and, thereby, were independent of an action on K+ channels. Reduction of extracellular K+ or Cl- attenuated furosemide-mediated relaxation of, and inhibition of 86Rb+ uptake by, PV even in the presence of ouabain. It was concluded that furosemide relaxes veins by an effect on Na+/K+/Cl- cotransport or chloride-mediated refilling of intracellular calcium stores.
Greenberg
S
S
Department of Medicine, Physiology and Pharmacology, LSU Medical Center, New Orleans.
McGowan
C
C
Xie
J
J
Summer
W R
WR
D000818:Animals; D001158:Arteries / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D001692:Biological Transport; D002712:Chlorides / Q000378:metabolism; D004285:Dogs; D004730:Endothelium, Vascular; D005260:Female; D005665:Furosemide / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D011188:Potassium / Q000378:metabolism; D015221:Potassium Channels / Q000502:physiology; D011651:Pulmonary Artery / Q000187:drug effects; D011667:Pulmonary Veins / Q000187:drug effects; D012413:Rubidium / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D014680:Veins / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology
D002712:Chlorides; D015221:Potassium Channels; D009020:Morphine; D005665:Furosemide; D000254:Sodium-Potassium-Exchanging ATPase; D012413:Rubidium; D011188:Potassium