Cardiovascular effects of the K-ATP channel blocker U-37883A and structurally related morpholinoguanidines.
Methods Find Exp Clin Pharmacol
; 18(4): 247-60, 1996 May.
Article
em En
| MEDLINE
| ID: mdl-8803957
ABSTRACT
The cardiovascular effects of the K-ATP channel blocker U-37883A and 5 related morpholinoguanidines were determined in 6 experimental preparations. In anesthetized dogs, U-37883A (0.5-8.0 mg/kg i.v.) increased mean arterial pressure (MAP; +18%) and left ventricular (LV) effective refractory period (ERP; +35%), and decreased LV contractility (-41%). Higher doses of U-37883A (16-32 mg/kg) fatally reduced MAP (-84%), heart rate (HR; -57%) and LV contractility (-72%). In anesthetized rats, U-37883A (1.0-50 mg/kg i.v.) also maximally reduced MAP, HR and LV contractility by 68, 77 and 48%, respectively. U-37883A and its analogs were diuretic in conscious rats (1.5-15 mg/kg i.v.) and blocked pinacidil in rabbit mesenteric artery (EC50 = 0.5-50 microM). In rabbit papillary muscle, 50 microM U-37883A significantly reduced force of contraction (-33%) and prolonged conduction time (+244%). Milder papillary effects were seen with the N'-OH analog U-45194A, which did not depress LV contractility in intact rats. In conscious dogs, oral U-45194A (50 mg/kg) was diuretic but reduced LV stroke volume and increased peripheral vascular resistance. These studies characterize U-37883A's systemic cardiovascular and direct myocardial effects, and identify U-45194A as a less cardiac depressant analog having U-37883A-like diuretic and functional K-ATP channel blocking activities.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Adamantano
/
Canais de Potássio
/
Morfolinas
/
Diuréticos
Idioma:
En
Revista:
Methods Find Exp Clin Pharmacol
Ano de publicação:
1996
Tipo de documento:
Article
País de afiliação:
Estados Unidos