This study was designed to investigate the role of vasopressin and angiotensin II in the pathogenesis of focal glomerulosclerosis (FGS). A non- peptide vasopressin V1 antagonist (OPC-21268) and an angiotensin converting enzyme inhibitor (ACE-I) were administered either alone or in combination for 15 weeks to FGS, spontaneously hypercholesterolaemic rats. Treatment with the V1 antagonist (1% OPC-21268) suppressed the rise in systolic blood pressure (SBP), serum triglyceride (TG), blood urea nitrogen (BUN) and serum creatinine (S-Cr) levels, but not the elevations of urinary protein excretion (UPE) or serum total cholesterol (TC) levels. Morphologically, V1 antagonist significantly prevented an increase in the index of glomerular sclerosis (IS) and relative interstitial volume (RIV). In the low dose/high dose of V1 antagonist supplementation, the administration of 0.2% OPC-21268 failed to suppress any increase in the SBP and TG levels, but significantly preserved renal function and attenuated renal lesions. In the combination study, rats were divided into four groups: (i) V1 antagonist (1% OPC-21268); (ii) ACEI (imidapril, 5 mg/kg/per day); (iii) both treated groups; and (iv) an untreated control group. Angiotensin-converting enzyme inhibitor significantly suppressed increases in SBP, UPE, TC, BUN, and S-Cr levels compared with V1 antagonist. The combination therapy significantly enhanced these effects. Both agents significantly reduced IS and RIV, and combination therapy further reduced these levels. The results indicated that vasopressin, as well as angiotensin II, via the V1 receptor cause hypertension and renal injury in FGS rats. V1 antagonist and ACEd have antihypertensive and renoprotective effects in this FGS model, and enhanced their beneficial effects when used as combination therapy.
|Number of pages||11|
|Publication status||Published - 1997|
- Angiotensin converting enzyme inhibitor
- Focal glomerulosclerosis
- Spontaneously hypercholesterolaemic rat
- Vasopressin V1 antagonist
ASJC Scopus subject areas