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Department of Pharmacology, Faculty of Medicine, University of Tokyo, Japan.

1. We studied the effect of servo-controlled stretch of smooth muscle strips from rat uterus on tension and intracellular Ca2+ concentration ([Ca2+]i, using fura-2 as an indicator) at 30 degrees C. 2. When quiescent uterine muscle strips were stretched at a ramp time of 0.5 s by multiples of 5% of the resting muscle length (L0) up to 40%, forty-two out of sixty muscle strips responded with a transient active contraction and a [Ca2+]i increase. The minimum excursion of stretch required for contraction was 26.3 +/- 7.5% of L0 (mean +/- S.D.). The peak response had an all-or-none property and was almost independent of the duration of stretch. 3. Stretches of 30 or 35% of L0 induced contraction in most cases when rapidly applied in 0.2-0.5 s, but slowly applied stretch (ramp duration of 5-10 s) rarely induced contraction. 4. The stretch-induced response was inhibited by the removal of extracellular Ca2+ or by the addition of 10 nM nicardipine. However, it was unaffected by 1 microM tetrodotoxin, 1 microM atropine or by 10 microM cyclopiazonic acid, an inhibitor of Ca2+-ATPase in intracellular Ca2+ stores. 5. When a stretch of 15-35% of L0 was applied during the relaxation phase of 10 nM oxytocin-induced rhythmic contractions, the first contraction after the stretch occurred earlier than that expected from the control rhythm. However, the frequency of the subsequent rhythm returned to almost the control level even during continued application of stretch, although the half-width of rhythmic contractions was increased during stretch. 6. The present study demonstrates that stretch of uterine muscle induces a transient contraction due to Ca2+ influx, which is myogenic and dependent on the excursion and velocity of stretch. The all-or-none property of the stretch-induced contractions suggests initiation of Ca2+ spikes. Furthermore, stretch modulates the oxytocin-induced rhythmic contractions.

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