The XXXX /Soluble Cyclic Guanylase/Cyclic Guanosine Monophosphate Pathway Is Involved in the Cardiovascular Effects of a Novel a1- and b-Adrenoceptor Antagonist.

@entity3773 @entity1405 @entity842 @entity460 @entity35 @entity551 @entity15497
UNASSIGNED: The compound MH-78 ((+/-)-1-(2,6-dimethylphenoxy)-3-{4-[2-(2-methoxyphenoxy)ethyl]-piperazin-1-yl}propan-2-ol dihydrochloride) contains structural elements that are typical for a1- and b-blockers. This study aimed to investigate the @entity551 activity as well as the in vitro and in vivo cardiovascular effects of a novel a1- and b-adrenoceptor antagonist (MH-78) and compare it with @entity1405 and @entity3773 . The procedures were performed on aortic rings of normotensive anesthetized @entity35 . MH-78 decreased the blood pressure and heart rate after intravenous and oral administration. MH-78 possesses both a1- and b-adrenoceptor blocking activity, which was confirmed in the in vivo study. In biofunctional assays, MH-78 displayed vasorelaxant activity due to a1-adrenoceptor antagonism and @entity460 channel blocking properties. Moreover, in endothelium-intact aortic rings, pretreatment with N  -nitro-L-arginine methyl ester (L-NAME) and @entity15497 (ODQ) reduced the MH-78-induced vasorelaxation to a level that is characteristic for MH-78 affinity to a1-adrenoceptors. Our results demonstrated that MH-78 possesses a1- and b-adrenoceptor blocking properties and induces potent @entity551 and vasorelaxant effects. Moreover, it relaxes vascular smooth muscle not only due to a1-adrenoceptor blocking activity, but also via the endothelium-dependent @entity842 /soluble guanylyl cyclase/cyclic guanosine monophosphate signalling pathway.    2014 S. Karger AG, Basel.
