tretinoin and candesartan

Topics: Alitretinoin; Androgens; Angiotensin Receptor Antagonists; Animals; Benzimidazoles; Biphenyl Compounds; Cholecalciferol; DNA-Binding Proteins; Drug Design; Genistein; Humans; Male; Neoplasms, Hormone-Dependent; Prostatic Neoplasms; Receptor, Angiotensin, Type 1; Receptors, Angiotensin; Telomerase; Tetrazoles; Tretinoin

We previously demonstrated that all-trans retinoic acid (RA) preserves glomerular structure and function in anti-Thy1.1 nephritis (Wagner J, Dechow C, Morath C, Lehrke I, Amann K, Floege J, and Ritz E. J Am Soc Nephrol 11: 1479-1489, 2000). Because the renin-angiotensin system (RAS) contributes to renal damage, we 1) studied retinoid-specific effects on its components and 2) compared the effects of all-trans-RA with those of the AT(1)-receptor blocker candesartan. Rats were pretreated for 3 days before injection of the OX-7 antibody and continued with treatment with either vehicle or daily injections of 10 mg/kg all-trans-RA only (study 1) or 10 mg/kg body wt all-trans-RA, 1 mg/kg candesartan, or both (study 2) for an additional 7 days. The blood pressure increase observed in anti-Thy1.1 nephritic rats was equally normalized by all-trans-RA and candesartan (P < 0.05). In nephritic rats, mRNAs of angiotensinogen and angiotensin-converting enzyme (ACE) in the kidney were unchanged, but renin mRNA was lower (P < 0.01). Renal and glomerular AT(1)-receptor gene and protein expression levels were higher in anti-Thy1.1 nephritic rats (P < 0.05). In the renal cortex of nephritic rats, pretreatment with all-trans-RA significantly reduced mRNAs of all the examined RAS components, but in the glomeruli it increased ACE gene and protein expression (P < 0.01). In nephritic rats, candesartan reduced the number of glomerular cells and mitoses (P < 0.05) less efficiently than all-trans-RA (P < 0.01). Both substances reduced cellular proliferation (proliferating cell nuclear antigen) significantly (P < 0.05). No additive effects were noted when both compounds were combined. In conclusion, all-trans-RA influences the renal RAS in anti-Thy1.1 nephritis by decreasing ANG II synthesis and receptor expression. The beneficial effect of retinoids may be explained, at least in part, by reduction of RAS activity.

Topics: Angiotensin II; Angiotensin Receptor Antagonists; Angiotensinogen; Animals; Antibodies; Benzimidazoles; Biphenyl Compounds; Blood Pressure; Kidney; Kidney Glomerulus; Male; Nephritis; Peptidyl-Dipeptidase A; Proto-Oncogene Proteins c-fos; Rats; Rats, Wistar; Receptor, Angiotensin, Type 1; Receptors, Mineralocorticoid; Renin; Renin-Angiotensin System; RNA, Messenger; Tetrazoles; Thy-1 Antigens; Tretinoin