Effects of furosemide on the neuromuscular junction.
These studies investigated the direct effects of furosemide on neuromuscular transmission using the in vitro rat phrenic nerve diaphragm and the in vivo at soleus nerve muscle preparations. Furosemide (10(-6)-10(-4)m) reduced the concentration of d-tubocurarine required to achieve 50% twitch tension depression in the indirectly stimulated rat diaphragm. Intraarterial injection of furosemide had a biphasic effect on the cat neuromuscular junction. At low doses (0.1-10.0 micrograms/kg) the drug had a depressant effect, reduced the force of muscle contraction, prevented nerve and muscle responses to NaF and dibutryl cyclic AMP, and intensified the neuromuscular blockade produced by d-tubocurarine and succinylcholine. In contrast, in higher doses (1-4 mg/kg) furosemide produced stimulus-bound repetitive neural activity, initiated neural activity, increased the force of muscle contraction, enhanced nerve and muscle responses to NaF and dibutyrl cyclic AMP, and antagonized d-tubocurarine and succinylcholine blockades. Furosemide had no effect on denervated preparations. High doses of furosemide inhibit non-competitively both the high- and low-affinity forms of the enzyme cyclic AMP phosphodiesterase in both soluble and particulate fractions of cat sciatic nerve. Thus, furosemide has direct effects on neuromuscular transmission, but the direction of these effects is dose-dependent.
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000378:metabolism; D000818:Animals; D002415:Cats; D004305:Dose-Response Relationship, Drug; D005665:Furosemide / Q000008:administration & dosage*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009469:Neuromuscular Junction / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D012969:Sodium Fluoride / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects*; D013806:Theophylline / Q000494:pharmacology; D014403:Tubocurarine / Q000494:pharmacology
D005665:Furosemide; D012969:Sodium Fluoride; D013806:Theophylline; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D014403:Tubocurarine