RESUMO
This study was designed to investigate the alternation of blood vessel relaxation in chronic renal failure (CRF) induced by adenine or partial-nephrectomy. The aorta was employed as the blood vessel material. CRF aorta relaxation in both adenine and partial nephrectomy induced rats increased when treated with glyceryl trinitrate (GTN). In the CRF animals, cGMP levels increased with the severity of CRF status. Aorta cytosolic glutathione S-transferase micro (GSTmicro) activity and enzyme contents increased with CRF. The effect of GTN on aortic vasorelaxation in both CRF statuses completely disappeared by the treatment with sodium nitoprusside. The effects of GTN were observed equally in both adenine- and partial nephrectomy-induced CRF rats. We concluded that alterations of aortic vasorelaxation by GTN in adenine- and partial nephrectomy-induced renal failure rats were caused by the enhancement of nitrogen monoxide production on the aortic blood vessel mediated by the induced GSTmicro in the aorta. This GSTmicro induction is peculiar to CRF since different CRF induction procedures produce the same results.
Assuntos
Hidrocarboneto de Aril Hidroxilases , Sistema Enzimático do Citocromo P-450/metabolismo , Glutationa Transferase/metabolismo , Falência Renal Crônica/fisiopatologia , Nitroglicerina/farmacologia , Oxirredutases N-Desmetilantes/metabolismo , Vasodilatação/efeitos dos fármacos , Adenina , Animais , Aorta/efeitos dos fármacos , Aorta/enzimologia , Nitrogênio da Ureia Sanguínea , GMP Cíclico/biossíntese , Citocromo P-450 CYP3A , Modelos Animais de Doenças , Falência Renal Crônica/enzimologia , Falência Renal Crônica/etiologia , Masculino , Nefrectomia , Nitroprussiato/farmacologia , Ratos , Ratos Sprague-DawleyRESUMO
The systemic availability of nicardipine after different routes of administration has been examined in rats, with particular attention to differentiating oral absorption from intestinal and hepatic metabolism. The quantities of nicardipine and its metabolite were determined by capillary column gas chromatography. A linear relationship was shown between the hepatic first-pass effect and dose after hepato-portal administration of nicardipine; the hepatic first-pass effect was calculated to be approximately 80%. However, the availability after oral and rectal administration was found to be more than twice that observed after hepato-portal administration. Partial avoidance of the hepatic first-pass effect after oral and rectal administration are estimated to be 37.3% and 35.2%, respectively, assuming that all absorbed molecules pass through the liver. These findings suggest that the absorption of nicardipine after oral administration also occurs by routes other than the hepato-portal system.
