ENDOTHELIAL-CELL PRODUCTS ALTER MAMMALIAN SKELETAL-MUSCLE FUNCTION IN-VITRO

We tested the hypothesis that endothelin and nitric oxide (NO) alter t he force developed by fast-twitch and slow-twitch mammalian skeletal m uscle, using a mouse skeletal muscle preparation trimmed to approximat ely 50% of the original diameter to decrease diffusion distances. We s uspended trimmed soleus (SOL) and extensor digitorum longus (EDL) musc les in Krebs-Henseleit buffer (27 degrees C; pH 7.4) gassed with 95% O -2 - 5% CO2. Muscles were stimulated once every 90 s for 500 ms at 50 Hz for SOL and 100 Hz for EDL. The force developed by trimmed SOL was 223.8 +/- 9.1 mN/mm(2) and by EDL was 247.3 +/- 9.4 mN/mm(2). Endothel in 1 (ET-1) had no effect on EDL but significantly accelerated the rat e of decrease of developed force of SOL at concentrations of 10(-10) m ol/L and higher within 10 contractions. When ET-1 was removed, force r eturned toward control value. Endothelin 3 (ET-3) had no effect on eit her muscle. S-Nitroso-N-acetylpenicillamine (SNAP), a source of NO, in creased developed force over time in both muscles, with a threshold of 10(-6) mol/L. The effect was evident within 5 contractions in both mu scles. Force remained elevated above control values after the removal of SNAP. Thus ET-1 attenuated and NO amplified mammalian skeletal musc le function.