Role of NO-cGMP pathway in ovine cervical relaxation induced by Erythroxylum caatingae Plowman

Erythroxylum caatingae Plowman has a myorelaxing effect on smooth muscle tissue. We investigated the effect of the crude ethanolic extract of E. caatingae Plowman (Ec-EtOH) on the contractility of the ovine cervix. In an isometric system, circular strips were subjected to 90mM potassium (K(+)) or 30μM carbamylcholine (CCh)-induced contraction. We then exposed the tissue to cumulative concentrations of Ec-EtOH (1-729 μg/ml). In other bath solutions, the tissues were exposed to l-NG-nitroarginine methyl ester (l-NAME; 100μM), l-NAME (100μM)+l-arginine (300μM), 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, ODQ; 5μM), 4-aminopyridine (4-AP; 3mM), tetraethylammonium (TEA; 0.3mM), glybenclamide (1μM), atosiban (10μM) or verapamil (3μM), followed by the addition of Ec-EtOH (1-729 μg/ml). We also evaluated the effect of cervical Ec-EtOH infusion (2mg) on cervical contractility in vivo. Ec-EtOH decreased cervical contractility induced by K(+) or CCh, and 729 μg/ml Ec-EtOH decreased 85.4±5.1% the amplitude of basal contractility in vitro, with an EC50 of 17.9±3.7 μg/ml. This effect of Ec-EtOH was prevented by l-NAME or ODQ. l-arginine impaired the blunting effect of l-NAME on cervical relaxation caused by Ec-EtOH. However, the potassium channel blockers 4-AP, TEA, and glybenclamide did not modify this myorelaxation triggered by Ec-EtOH. Ec-EtOH also decreased acetylcholine-induced contractions in tissue preincubated with verapamil. In addition, Ec-EtOH decreased ovine cervical contractions in vivo. Thus, Ec-EtOH had a relaxant effect on ovine cervical contractions. This may involve the nitric oxide signal, mediated by cGMP cellular transduction, and be related to intracellular calcium sequestration.