Influence of Furosemide on Rubidium-86 Uptake and Alpha-Adrenergic Responsiveness of Arterial Smooth Muscle

Abstract

Furosemide-induced inhibition of ⁸⁶Rb uptake was measured in rat and rabbit aorta and compared with its ability to inhibit contractions induced by α-adrenergic agonists. In both rat and rabbit tissues, furosemide defined a portion of ⁸⁶Rb uptake (IC₅₀ = 2.5 µ M) which was distinct from the ouabain-sensitivite 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.