Skeletal muscle force and actomyosin ATPase activity reduced by nitric oxide donor.
Nitric oxide (NO) may exert direct effects on actin-myosin cross-bridge cycling by modulating critical thiols on the myosin head. In the present study, the effects of the NO donor sodium nitroprusside (SNP; 100 microM to 10 mM) on mechanical properties and actomyosin adenosinetriphosphatase (ATPase) activity of single permeabilized muscle fibers from the rabbit psoas muscle were determined. The effects of N-ethylmaleimide (NEM; 5-250 microM), a thiol-specific alkylating reagent, on mechanical properties of single fibers were also evaluated. Both NEM (>/=25 microM) and SNP (>/=1 mM) significantly inhibited isometric force and actomyosin ATPase activity. The unloaded shortening velocity of SNP-treated single fibers was decreased, but to a lesser extent, suggesting that SNP effects on isometric force and actomyosin ATPase were largely due to decreased cross-bridge recruitment. The calcium sensitivity of SNP-treated single fibers was also decreased. The effects of SNP, but not NEM, on force and actomyosin ATPase activity were reversed by treatment with 10 mM DL-dithiothreitol, a thiol-reducing agent. We conclude that the NO donor SNP inhibits contractile function caused by reversible oxidation of contractile protein thiols.
Perkins
W J
WJ
Department of Anesthesiology, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA.
Han
Y S
YS
Sieck
G C
GC
D000477:Alkylating Agents / Q000494:pharmacology; D000818:Animals; D004229:Dithiothreitol / Q000494:pharmacology; D005033:Ethylmaleimide / Q000494:pharmacology; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects / Q000502:physiology; D009119:Muscle Contraction / Q000502:physiology; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000502:physiology; D018482:Muscle, Skeletal / Q000187:drug effects / Q000201:enzymology* / Q000502:physiology*; D009218:Myosins / Q000378:metabolism*; D009569:Nitric Oxide / Q000502:physiology*; D009599:Nitroprusside / Q000494:pharmacology*; D016658:Psoas Muscles / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D011817:Rabbits; D019141:Respiratory System Agents / Q000494:pharmacology; D013438:Sulfhydryl Compounds / Q000378:metabolism
D000477:Alkylating Agents; D019141:Respiratory System Agents; D013438:Sulfhydryl Compounds; D009599:Nitroprusside; D009569:Nitric Oxide; D009218:Myosins; D005033:Ethylmaleimide; D004229:Dithiothreitol