Influence of furosemide on rubidium-86 uptake and alpha-adrenergic responsiveness of arterial smooth muscle.
Furosemide-induced inhibition of 86Rb uptake was measured in rat and rabbit aorta and compared with its ability to inhibit contractions induced by alpha-adrenergic agonists. In both rat and rabbit tissues, furosemide defined a portion of 86Rb uptake (IC50 = 2.5 microM) which was distinct from the ouabain-sensitive fraction. Furosemide-sensitive 86Rb uptake was [Cl-]ext dependent and required Na+ and K+ for optimal activity, suggesting that it reflected a Na+-K+ cotransport process. Furosemide-sensitive 86Rb uptake was found to be greater in HEPES buffer than in bicarbonate buffer. Phenylephrine-induced contractions of rat and rabbit aorta were inhibited by furosemide; however, rat responses were far more sensitive. Agonist-induced uptake of 45Ca was reduced by furosemide in rat aorta, but not in rabbit aorta. Agonist-induced 45Ca efflux stimulation was reduced in both species. These findings indicate the presence in arteries of a furosemide-sensitive, Cl-dependent Na+-K+ cotransport process. Along with other monovalent transport processes, it may modulate Ca2+ availability and thereby influence arterial contractility.
Deth
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RC
Section of Pharmacology, College of Pharmacy and Allied Health Professions, Northeastern University, Boston, Mass.
Payne
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RA
Peecher
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DM
D000818:Animals; D001011:Aorta / Q000378:metabolism; D001693:Biological Transport, Active / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002712:Chlorides / Q000378:metabolism; D005665:Furosemide / Q000494:pharmacology*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D010042:Ouabain / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology*; D011188:Potassium / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects* / Q000502:physiology; D012414:Rubidium Radioisotopes / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000378:metabolism
D002712:Chlorides; D011942:Receptors, Adrenergic, alpha; D012414:Rubidium Radioisotopes; D010656:Phenylephrine; D010042:Ouabain; D005665:Furosemide; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium; D002118:Calcium