title: Pharmacological activity of novel 2-hydroxyacetophenone isatin derivatives on cardiac and vascular smooth muscles in rats.
abstract: Isatin (1H-indole-2,3 dione) is an endogenous compound with biological activities. Many of its derivatives have pharmacological effects, including inhibition of cyclic guanosine monophosphate levels in cardiac tissue; sedative-hypnotic profiles; anticonvulsant, analgesic, antithermic, and anti-inflammatory activities; and anxiolytic, antimicrobial, and proapoptotic effects. Carbamates derived from isatin have a vasorelaxant profile. This study investigated the activity of 2 novel 2-hydroxyacetophenone derivatives of isatin (named MB101 and MB130) on the contractility of rat aorta and papillary muscles. Both compounds induced a concentration-dependent relaxation (5-100 μM) in the endothelium-intact aorta that was abolished by N-nitro-L-arginine methyl ester. Atropine, a muscarinic receptor antagonist, significantly prevented vasodilatation of 100 μM MB101. In contrast, atropine caused no significant alteration in MB130-induced vasorelaxation. Naloxone, a nonselective opioid receptor antagonist, completely prevented the relaxing effect of MB101 and MB130 at all concentrations. In papillary muscles, only MB130 induced a significant depression, and this contractile response was not altered by propranolol and atropine. Both the compounds reduced systolic and diastolic pressures in a dose-dependent manner in anesthetized rats. The 2-hydroxyacetophenones produced direct effects on vascular tonus through either muscarinic or opioid pathways. MB130 produced cardiac depression by opioid receptors and bradykinin because pretreatment HOE140 or with naloxone, an antagonist of type-2, bradykinin were able to partially block the decrease in twitch amplitude in papillary muscles induced by MB130. These findings provide information for designing new strategies for the treatment of cardiovascular disorders.
authors.affiliation: Programa de Desenvolvimento de Fármacos, Universidade Federal do Rio de Janeiro, Instituto de Ciências Biomédicas, Rio de Janeiro, Brazil.
authors.forename: Daniele
authors.initials: D
authors.lastname: Gabriel
authors.forename: Luana Braga
authors.initials: LB
authors.lastname: Pontes
authors.forename: Jaqueline Soares
authors.initials: JS
authors.lastname: da Silva
authors.forename: Roberto Takashi
authors.initials: RT
authors.lastname: Sudo
authors.forename: Marilza Baptista
authors.initials: MB
authors.lastname: Corrêa
authors.forename: Angelo C
authors.initials: AC
authors.lastname: Pinto
authors.forename: Simon John
authors.initials: SJ
authors.lastname: Garden
authors.forename: Gisele
authors.initials: G
authors.lastname: Zapata-Sudo
mesh_terms: D000098:Acetophenones / Q000494:pharmacology*; D000818:Animals; D058633:Antipyretics / Q000378:metabolism; D001120:Arginine / Q000494:pharmacology; D001920:Bradykinin / Q000378:metabolism / Q000494:pharmacology; D006152:Cyclic GMP / Q000378:metabolism; D006321:Heart / Q000187:drug effects*; D007510:Isatin / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000378:metabolism / Q000494:pharmacology
chemical_list: D000098:Acetophenones; D058633:Antipyretics; D014665:Vasodilator Agents; C087908:2'-hydroxyacetophenone; D007510:Isatin; D001120:Arginine; D006152:Cyclic GMP; D001920:Bradykinin