These results show that levosimendan effectively and directly decreases the tone of the HUA. The mechanism of this levosimendan-induced relaxation in the HUA appears in part to be due to voltage-gated and large conductance Ca2+-activated K+ channel opening action.

No abstract

We investigated the functional effects of glucagon-like peptide-1 [GLP-1(7-36)] and GLP-1(9-36) and the mechanism(s) playing a role in the effects of these agents in isolated small resistance arteries from control and diabetic rats. Cumulative concentrations of GLP-1(7-36) and GLP-1(9-36) produced concentration-dependent relaxations in endothelium-intact but not endothelium-denuded arteries that were significantly decreased in diabetic rats. GLP-1 receptor antagonist exendin(9-39) significantly inhibited responses to GLP-1 analogs. Nitric oxide/cyclic guanosine monophosphate pathway blockers, but not indomethacin, significantly decreased responses to GLP-1(7-36) or GLP-1(9-36) in control and diabetic rats. 4-Aminopyridine or glibenclamide incubation did not alter relaxations to GLP-1 analogs. GLP-1(7-36)- and GLP-1(9-36)-induced relaxations were blunted significantly and to similar extends by charybdotoxin and apamin combination in control and diabetic rats. Catalase did not affect, whereas superoxide dismutase (SOD) caused a significant increase in relaxations to GLP-1 analogs only in diabetic rats. We provided evidence about the relaxant effects of GLP-1(7-36) and GLP-1(9-36) in resistance arteries that were reduced in diabetic rats. Both calcium-activated potassium channels and endothelium played a major role in relaxations. Increment in certain reactive oxygen species and/or reduction in superoxide dismutase function might play a role in reduced relaxant responses of resistance arteries to GLP-1(7-36) and GLP-1(9-36) in diabetic rats.

Local anaesthetics, opioids and adjuvants are often used for managing labor pain. Some others of these agents are reported to cause alterations on uterine contractility during labor. However, there are controversies and the effects of some others are unknown. In the present study, we aimed to elucidate the effects of opioids such as alfentanyl, meperidine, remifentanyl; local anesthetics such as mepivacaine, ropivacaine, bupivacaine; and adjuvants such as clonidine and midazolam on isolated pregnant rat uterine muscle. Strips of longitudinal uterine smooth muscle obtained from rats pregnant for 18-21 days were suspended in 20 ml organ baths. Isometric tension was continuously measured with an isometric force transducer connected to a computer-based data acquisition system. The effects of cumulative concentrations of alfentanyl, meperidine, remifentanyl, mepivacaine, ropivacaine, bupivacaine, clonidine and midazolam (10(-8) - 10(-4) M, for all) on contractions induced by oxytocin (1 mU/ml) were studied. Alfentanyl (10(-5) M), meperidine (10(-5) M), remifentanyl (10(-4) M), bupivacaine (10(-4) M), ropivacaine (10(-4) M) and midazolam (3 x 10(-5) M) caused significant decreases in contractile responses of uterine strips to oxytocin. Contrastingly, mepivacaine increased (33.1% +/- 7.2%) oxytocin-induced contractions of uterine strips while clonidine exerted no significant effect. The sensitivity of myometrial preparations to tested local anesthetics or opioids did not differ significantly. The findings of the present study demonstrated that some local anesthetics, opioids and adjuvants caused significant and agent-specific alterations on contractility of the pregnant rat myometrium. Therefore, they seemed to have a potential to influence uterine contractility during clinical management of pain during labor. However, further research is needed to extrapolate these finding to clinical practice.