Objectives: A number of reports have shown that exogenous b-NAD+ inhibits spontaneous contractions and smooth muscle tone in the human urinary bladder (1). The purpose of the study was to investigate the effect of exogenous b-NAD+ on human myometrium contraction in vitro. Materials and Methods: Human myometrial tissue was obtained from non-pregnant and pregnant women after hysterectomy and caesarean section respectively. Myometrial strips (8-12 mg) were used for isometric tension recording. The effect of b-NAD+ was tested on spontaneous as well as on oxytocin induced contractions. Total RNA was extracted from the tissue, and followed by cDNA synthesis. PCR was performed using specific primers for small-conductance Ca2+ activated potassium channels (SK channels) SK2 and SK3. Results: We observed spontaneous uterine contractions in both experimental groups. b-NAD+ caused a concentration dependent decrease in spontaneous contractions as well as in oxytocin induced contractions. Apamin (1 mM), an inhibitor of SK channels, led to an increase in myometrial contractility in non pregnant myometrial strips. However, in the presence of apamin, the reduction of contractility caused by b-NAD+ was significantly lower than in spontaneous and oxytocin induced groups. PCR showed the presence of mRNA for SK2 and SK3 channels in the myometrium of both pregnant and non-pregnant women. Conclusions: Our data show for the first time that exogenous b-NAD+ induces a significant reduction in spontaneous and oxytocin induced myometrial contractility. In the presence of apamin, the effect of b-NAD+ was decreased significantly. We also show the presence of SK2 and SK3 channels in human myometrium. We conclude that b-NAD+ induced muscle relaxation is probably due to hyperpolarization of the cell membrane through activation of SK channels. However, the precise mechanism responsible for this effect has yet to be determined. 1) Breen LT, et al. Am J Physiol Renal Physiol. 2006 Feb;290(2): F486-95.