Effects of OPC-21268, a vasopressin V1-receptor antagonist, on expression of growth factors from glomeruli in spontaneously hypertensive rats.
To assess the chronic in vivo effects of OPC-21268, a vasopressin-V1 receptor antagonist, on renal injury, we investigated the mRNA expressions of platelet-derived growth factor (PDGF) B-chain, transforming growth factor (TGF)-beta1 and proliferating cell nuclear antigen (PCNA) in the glomeruli of spontaneously hypertensive rats (SHR) treated with OPC-21268 for 3 weeks. SHR aged 10 weeks were given 2% NaCl in drinking water for 3 weeks. The OPC group was fed a 0.5% OPC-21268-containing diet for 3 weeks and the control group was given a normal diet. There were no significant changes in the time course of systolic blood pressure, heart rate, urine volume, or urinary sodium, protein and N-acetyl-beta-glucosaminidase (NAG) excretion between the two groups. Serum electrolytes, protein and creatinine levels also did not differ between the groups. The mRNA expressions of PDGF B-chain, TGF-beta1 and PCNA in the glomerulus were examined using reverse transcriptase-polymerase chain reaction (RT-PCR) methods. The mRNA expressions of PDGF B-chain and PCNA among these were significantly suppressed in the OPC group. No significant differences in renal histology including the organ weights were found between the two groups; however, the glomerular size tended to be enlarged in the OPC group. These findings suggest that chronic V1-receptor blockade directly inhibits the glomerular proliferative injury of salt-loaded SHR at the established hypertension stage.
Otsuka
F
F
Department of Medicine III, Okayama University Medical School, Japan.
Ogura
T
T
Yamauchi
T
T
Oishi
T
T
Hashimoto
M
M
Mimura
Y
Y
Makino
H
H
D000118:Acetylglucosaminidase / Q000652:urine; D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D006133:Growth Substances / Q000096:biosynthesis* / Q000235:genetics; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000378:metabolism*; D007678:Kidney Glomerulus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D010880:Piperidines / Q000494:pharmacology*; D010982:Platelet-Derived Growth Factor / Q000096:biosynthesis / Q000235:genetics; D016133:Polymerase Chain Reaction; D018809:Proliferating Cell Nuclear Antigen / Q000096:biosynthesis / Q000235:genetics; D011507:Proteinuria; D015363:Quinolones / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D011897:Random Allocation; D051381:Rats; D011918:Rats, Inbred SHR; D012964:Sodium / Q000652:urine; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000235:genetics; D014556:Urine
D065092:Antidiuretic Hormone Receptor Antagonists; D006133:Growth Substances; D010880:Piperidines; D010982:Platelet-Derived Growth Factor; D018809:Proliferating Cell Nuclear Antigen; D015363:Quinolones; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; C068644:OPC 21268; D012964:Sodium; D000118:Acetylglucosaminidase