EFFECTS OF CGMP AND THE NITRIC-OXIDE DONORS GLYCERYL TRINITRATE AND SODIUM-NITROPRUSSIDE ON CONTRACTIONS IN-VITRO OF ISOLATED MYOMETRIAL TISSUE FROM PREGNANT-WOMEN

The purpose of this study was to determine the relaxant effects in vit ro of two nitric oxide donors, glyceryl trinitrate and sodium nitropru sside, which are currently available for use in vivo, on contract-ions of non-labouring myometrium from pregnant women. Since nitric oxide a lso mediates relaxation by increasing the concentration of cGMP, sensi tivity to 8-bromo-cGMP (a cGMP analogue) was also determined. The effe cts of the K+-channel opener lemakalim and of the Ca2+-channel blocker nifedipine were studied for comparison. After the addition of glycery l trinitrate (0.1-100 mu mol l(-1)), sodium nitroprusside (0.1-100 mu mol l(-1)) or 8-bromo-cGMP (0.001-3 mmol l(-1)), the spontaneous rhyth mic contractility of myometrial strips was inhibited in a concentratio n-dependent manner: the maximum inhibition produced by the highest tes ted concentration of each drug was 40 +/- 7%, 53 +/- 8% and 39 +/- 8% of the original degree of contraction, respectively. Myometrial contra ctions were completely abolished by lemakalim and by nifedipine and ve rapamil at concentrations of greater than or equal to 10(-5) mol l(-1) . The nitric oxide donors, glyceryl trinitrate and sodium nitroprussid e, attenuate myometrial contractions and are therefore useful as tocol ytic agents. However, at equimolar concentrations in vitro, the abilit y of glyceryl trinitrate and sodium nitroprusside to attenuate myometr ial contractions is less than that of lemakalin, nifedipine and verapa mil. Controlled trials are required to determine the side-effects and clinical efficacy of each of these agents in vivo.