Modification of the ß-Adrenoceptor Stimulation Pathway in Zucker Obese and Obese Diabetic Rat Myocardium.
Crit Care Med
; 43(7): e241-9, 2015 Jul.
Article
en En
| MEDLINE
| ID: mdl-26079096
ABSTRACT
OBJECTIVES:
Although metabolic syndrome is associated with increased sympathetic activity that chronically stimulates ß-adrenoceptors, the ß-adrenoceptor signaling pathway has been poorly studied in this situation. We studied the ß-adrenoceptor signaling pathway in Zucker lean, obese, and obese diabetic rats.DESIGN:
Experimental, prospective study.SETTING:
University medical research laboratory.SUBJECTS:
Adult male Zucker lean (control), obese, and obese diabetic rats.INTERVENTIONS:
The effects of ß-adrenoceptor stimulation were investigated in vitro in isolated left ventricular papillary muscles in control, obese, and obese diabetic rats. ß1-, ß2-, and ß3-adrenoceptors and multidrug resistance-associated protein 4 were quantified by Western Blotting. Triglyceride, cholesterol, leptin, adiponectin, and C-peptide plasma concentrations were measured. Data are mean ± SD. MEASUREMENTS AND MAINRESULTS:
Hyperlipidemia, high leptin, and C-peptide concentrations were observed in obese and obese diabetic strains, whereas hyperglycemia occurred only in the diabetic strain. The positive inotropic effect of isoproterenol was slightly reduced in obese rats (183% ± 11% of baseline; p = 0.003; n = 7) and markedly reduced in obese diabetic rats (137% ± 18% of baseline; p < 0.001; n = 10) when compared with control rats (210% ± 17% of baseline; n = 9). ß1-adrenoceptors were down-regulated in obese (-41%; p = 0.02) and diabetic (-54%; p = 0.003) when compared with control rats, whereas ß3-adrenoceptors and multidrug resistance-associated protein expression remained unchanged. Direct stimulation of adenylate cyclase with forskolin or administration of 3',5'-cyclic adenosine monophosphate suggests that subtle impairments also occurred beside the down-regulation of ß1-adrenoceptor.CONCLUSIONS:
The positive inotropic effect of ß-adrenoceptor stimulation is slightly decreased in Zucker obese rats and was more markedly decreased in Zucker diabetic rats. These decreases are mainly related to ß1-adrenoceptor down-regulation.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Transducción de Señal
/
Receptores Adrenérgicos beta
/
Diabetes Mellitus Experimental
/
Miocardio
/
Obesidad
Tipo de estudio:
Observational_studies
/
Risk_factors_studies
Límite:
Animals
Idioma:
En
Revista:
Crit Care Med
Año:
2015
Tipo del documento:
Article