Influence of autonomic nervous system on relaxant action of bisphenol A in porcine myometrium

The mechanism of action of bisphenol A (BPA) in the myometrium has not been fully understood, which is why an attempt was made to determine the involvement of the key mechanisms (cholinergic, adrenergic and non-cholinergic/non-adrenergic) that regulate the uterine contractile activity in the relaxant effect of this BPA in cyclic gilts. Strips of myometrium were incubated for 15 min with the Krebs-Ringer solution (K-Rs), acetylcholine (ACh), atropine, epinephrine, phentolamine, bupranolol, sodium nitroprusside (SNP), methylene blue (MB) or N-ω-nitro L-arginine methyl ester hydrochloride (L-NAME), and then incubated for 15 min with increasing (10-8-10-2 M) BPA concentrations. BPA administered at concentrations of 10-5-10-2 M, 10-3-10-2 M and 10-2 M after incubation with K-Rs, SNP and ACh and L-NAME, respectively, significantly reduced the uterine tension compared to the period before treatment. The amplitude of contractions was significantly reduced in myometrium pretreated with SNP and thereafter stimulated with BPA at concentrations of 10-3-10-2 M and pretreated with K-Rs, ACh, epinephrine, phentolamine, L-NAME and MB, and stimulated with BPA at a concentration of 10-2 M compared to the period before treatment. BPA administered after incubation with ACh, atropine and SNP significantly reduced the frequency of uterine contractions at concentrations of 10-7-10-2 M, after epinephrine and bupranolol at concentrations of 10-6-10-2 M, after MB at concentrations of 10-5-10-2 M, after K-Rs and phentolamine at concentrations of 10-3-10-2 M, and after L-NAME at a concentration of 10-2 M compared to the period before treatment. BPA at concentrations of 10-4-10-2 M significantly reduced the AUC value after prior administration of atropine, SNP and L-NAME, and at a concentration of 10-2 M after incubation with K-Rs, ACh, epinephrine, phentolamine, bupranolol and MB compared to the period before treatment. The results indicate that BPA's mechanism of action in the porcine myometrium is complex and that the final response to BPA's action results from multiple overlapping mechanisms of action. The autonomic system may slightly modify the action of BPA, with the nitrergic mechanism appearing to perform a more important role but with the guanyl cyclase/c-GMP mechanism being omitted.