| Popis: |
This study was designed to evaluate the protective effects of efonidipine, an L- and T-type calcium channelblocker, against hypertensive renal injuries in spontaneously hypertensive rats( SHR) chronically treatedwith N-nitro-L-arginine methyl ester( L-NAME), a nitric oxide synthase inhibiter. Four groups of seventeen-week-old male SHR were treated for as follows:the control group, the L-NAME group given80 mg/L L-NAME in drinking water, and the groups given 5( low-dose) or 20( high-dose) mg/kg/day efonidipineby gavage as well as 80 mg/L L-NAME in drinking. After three weeks, the rats were sacrificedand the degrees of renal injuries were compared. The L-NAME group developed renal dysfunction and renaltissue lesions such as glomerulosclerosis, arterial wall thickening and perivascular fibrosis and cell infiltrationwith the aggravation of hypertension. The high-dose efonidipine improved the renal function and alleviatedthe renal tissue lesions in SHR given L-NAME as well as lowering blood pressure. On the otherhand, the low-dose efonidipine also exhibited such renoprotective effects without causing significant changesof blood pressure in L-NAME-treated SHR. Renal cortical mRNA expressions of transforming growthfactor-b 1 (TGF-b 1) and peroxisome proliferator-activated receptor-g (PPAR-g) were increased and decreased,respectively, in SHR given L-NAME. Such changes in the mRNA expressions were mitigated byeither the low-dose or the high-dose efonidipine treatment. It is suggested that efonidipine is effective in inhibitingthe progression of hypertensive renal injuries and the renoprotective effects are mediated by themechanism independent of blood pressure reduction as well as by the antihypertensive action. |
