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.