Pharmacokinetics and pharmacodynamics of a nitric oxide-releasing derivative of enalapril in male beagles

dc.creatorOkuyama, CE
dc.creatorMendes, GD
dc.creatorFaro, R
dc.creatorRezende, VM
dc.creatorLagos, RM
dc.creatorAstigarraga, REB
dc.creatorAntunes, E
dc.creatorDe Nucci, G
dc.date2007
dc.dateAPR
dc.date2014-11-16T01:20:22Z
dc.date2015-11-26T16:31:14Z
dc.date2014-11-16T01:20:22Z
dc.date2015-11-26T16:31:14Z
dc.date.accessioned2018-03-28T23:12:17Z
dc.date.available2018-03-28T23:12:17Z
dc.identifierClinical And Experimental Pharmacology And Physiology. Blackwell Publishing, v. 34, n. 4, n. 290, n. 295, 2007.
dc.identifier0305-1870
dc.identifierWOS:000244227000007
dc.identifier10.1111/j.1440-1681.2007.04559.x
dc.identifierhttp://www.repositorio.unicamp.br/jspui/handle/REPOSIP/59400
dc.identifierhttp://www.repositorio.unicamp.br/handle/REPOSIP/59400
dc.identifierhttp://repositorio.unicamp.br/jspui/handle/REPOSIP/59400
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/1270156
dc.description1. Pharmacological compounds that release nitric oxide (NO) have been useful tools in the evaluation of the broad role of NO in physiopathology and therapeutics. The present study compared the pharmacokinetics and pharmacodynamics of enalapril and an NO-releasing enalapril molecule (NCX899) in conscious male beagles. The effects of both enalapril and NCX899 in the arterial hypertension and bradycardia induced by acute NO inhibition in anaesthetized dogs were also investigated. 2. Dogs received either NCX899 (4 mu mol/kg, i.v.) or enalapril (4 mu mol/kg, i.v.), after which plasma concentrations of the analytes and metabolites were quantified by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). 3. In the NCX899 group, the area under the time-course curve (AUC(0-24h)) was 29.18 +/- 4.72, 229.37 +/- 51.32 and 5159.23 +/- 514.88 mu g.h/L for the analytes nitro-enalapril, enalapril and enalaprilat, respectively. In the enalapril group, the AUC(0-24h) was 704.53 +/- 158.86 and 4149.27 +/- 847.30 mu g.h/L for the analytes enalapril and enalaprilat, respectively. Statistical analysis of data from both groups showed a significant difference for the analyte enalapril, but not for enalaprilat. Moreover, NCX899 and enalapril were equally effective in inhibiting the activity of serum angiotensin-converting enzyme. 4. In anaesthetized dogs, i.v. administration of the NO synthase (NOS) inhibitor N-G-nitro-L-arginine methyl ester (L-NAME; 0.1-10 mg/kg) significantly elevated arterial blood pressure, with concomitant bradycardia. The compound NCX899 significantly attenuated both arterial hypertension and bradycardia, whereas enalapril had no significant effect. 5. In conclusion, the present results showed that the NO-releasing derivative of enalapril NCX899 presents a pharmacokinetic/pharmacodynamic relationship similar to its parent compound enalapril. Moreover, NCX899 (but not enalapril) was effective in protecting against the cardiovascular changes induced by acute NOS inhibition.
dc.description34
dc.description4
dc.description290
dc.description295
dc.languageen
dc.publisherBlackwell Publishing
dc.publisherOxford
dc.publisherInglaterra
dc.relationClinical And Experimental Pharmacology And Physiology
dc.relationClin. Exp. Pharmacol. Physiol.
dc.rightsfechado
dc.sourceWeb of Science
dc.subjectangiotensin-converting enzyme
dc.subjecthypertension
dc.subjectnitro-enalapril
dc.subjectConverting-enzyme-inhibitor
dc.subjectRenin-angiotensin System
dc.subjectArginine Methyl-ester
dc.subjectAnesthetized Dogs
dc.subjectVascular-resistance
dc.subjectS-nitrosocaptopril
dc.subjectCardiac-output
dc.subjectHypertension
dc.subjectRats
dc.subjectDrugs
dc.titlePharmacokinetics and pharmacodynamics of a nitric oxide-releasing derivative of enalapril in male beagles
dc.typeArtículos de revistas


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