An investigation of the effects of H2S on myometrial function. (360G-Wellcome-086736_Z_08_Z)

Recent findings on the biological role of Hydrogen sulphide (H2S) have led to the suggestion that its role may be as significant as that of nitric oxide. In the studies to date made on smooth muscles a relaxant effect has generally been reported. In the field of uterine smooth muscle finding new tocolytic (relaxant) mechanisms and therapeutic targets is a major goal, as premature labour is the principle cause of neonatal mortality and a major cause of handicap. Very little however is known about how H2S can influence myometrial activity. The aims of this project are therefore to: 1) Measure Ca transients and contractility produced spontaneously, by high-K depolarization and via oxytocin stimulation in the presence of increasing amounts of H2S 2) Determine if responses to H2S are altered during pregnancy and labour 3) Examine in myometrium which enzymes are responsible for the production of H2S 4) Informed by the data obtained in the above aim, an investigation will be made into the mechanism by which H2S affects uterine activity by measuring membrane currents and/or myosin light chain phosphorylation, intracellular pH and sarcoplasmic reticular function.