Possible mechanisms of sudden death and hemoconcentration induced by endothelin-1 and big endothelin-1 in mice.
Biol Pharm Bull
; 17(5): 645-50, 1994 May.
Article
en En
| MEDLINE
| ID: mdl-7920424
ABSTRACT
We investigated the profiles of sudden death and hemoconcentration induced by endothelin-1 (ET-1) and big endothelin-1 (big ET-1) in mice using various compounds as pharmacological tools. In ET-1-induced sudden death (5 nmol/kg, i.v.), pretreatment with the Ca(2+)-channel blockers, diltiazem, nifedipine or verapamil at a dose of 2 mg/kg, i.v. significantly inhibited the mortality and prolonged the latency to death. These Ca(2+)-channel blockers, however, failed to inhibit the rise in hematocrit (Ht), namely hemoconcentration, induced by ET-1 (2.5 nmol/kg). A beta-adrenoceptor agonist, isoproterenol (1 mg/kg) tended to prolong the latency, whereas, a beta-adrenoceptor blocker, propranolol (2 mg/kg), and an alpha- and beta-adrenoceptor blocker, labetalol (5 mg/kg), aggravated the sudden death. Esculetin (10 mg/kg) and fenbufen (10 mg/kg), which are enzyme inhibitors in the arachidonate cascade, prevented only the hemoconcentration. Anti-arrhythmic drugs, lidocaine (1 mg/kg) and disopyramide (20 mg/kg) did not improve any parameters. Big ET-1 also caused sudden death (20 and 25 nmol/kg, i.v.) and hemoconcentration (10 nmol/kg, i.v.). Of several proteinase inhibitors, only a metalloproteinase inhibitor, phosphoramidon (2 mg/kg i.v.), prevented the sudden death and the hemoconcentration induced by big ET-1 but not by ET-1. Ca(2+)-channel blockers exerted their protective effects only when a lower dose of big ET-1 was employed. These results indicate that the sudden death caused by both peptide is mainly due to myocardial ischemia and respiratory disorder, and that hemoconcentration caused by them is due to their vasoconstrictor action but to their effects on the vascular permeability via secondary endogenous factors.
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Bases de datos:
MEDLINE
Asunto principal:
Precursores de Proteínas
/
Endotelinas
/
Muerte Súbita
Límite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
Biol Pharm Bull
Asunto de la revista:
BIOQUIMICA
/
FARMACOLOGIA
Año:
1994
Tipo del documento:
Article
País de afiliación:
Japón