The angiotensin I-converting enzyme inhibitor, cilazapril inhibits the platelet-derived growth factor B chain expression in glomeruli of spontaneously hypertensive rats.
To clarify whether in vivo expression of growth factors in the glomerulus is induced in a hypertensive animal model, we investigated the expression of platelet-derived growth factor (PDGF) B chain, transforming growth factor beta (TGF-beta), and angiotensin II (Ang II) type 1 receptors in glomeruli of spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats. We also investigated the effects of treatment with cilazapril, and angiotensin I-converting enzyme inhibitor, on this expression. First, the expression of PDGF B chain, TGF-beta, and Ang II receptors from the glomerulus were investigated using the reverse-transcriptase polymerase chain reaction in SHR and WKY rats. Although there was no significant difference in PDGF B chain, TGF-beta, and Ang II receptors from the glomerulus were investigated using the reverse-transcriptase polymerase chain reaction in SHR and WKY rats. Although there was no significant difference in PDGF B chain, TGF-beta or Ang II receptor expression between SHR and WKY rats at the age of 7 weeks, the PDGF B chain expression of 16-week-old SHR was significantly higher (4.4-fold) than that of age-matched WKY rats. Next, we administered oral cilazapril at a dose of 10 mg/kg to 13-week-old SHR daily for 3 weeks. The systolic blood pressure in SHR treated with cilazapril was significantly lower than that in control SHR. After administration of cilazapril for 3 weeks, we examined the in vivo expression of growth factors and Ang II receptors in the glomerulus. The PDGF B chain expression was suppressed by treatment with cilazapril (2.5-fold) as compared with nontreated SHR. No alteration in TGF-beta or Ang II receptor expression was detected. We did not find any histological changes in the kidneys of SHR, WKY rats or cilazapril-treated SHR, and cilazapril treatment did not suppress the glomerular size. These findings indicate that the expression of PDGF B chain in the glomerulus preceded the appearance of histological changes in SHR and that the administration of cilazapril inhibited the expression of PDGF B chain without affecting the glomerular size. This suggests that angiotensin I-converting enzyme inhibitors directly suppress the Ang II-induced PDGF B chain promotion in the glomerulus of SHR at the established hypertensive stage.
Yamauchi
T
T
3rd, Department of Internal Medicine, Okayama University Medical School, Japan.
Ogura
T
T
Oishi
T
T
Omiya
T
T
Ota
Z
Z
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D017315:Cilazapril / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000378:metabolism* / Q000473:pathology; D007678:Kidney Glomerulus / Q000378:metabolism* / Q000473:pathology; D010982:Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D020574:Proto-Oncogene Proteins c-sis; D051381:Rats; D011918:Rats, Inbred SHR / Q000378:metabolism*; D011921:Rats, Inbred WKY; D012016:Reference Values; D016212:Transforming Growth Factor beta / Q000378:metabolism
D000806:Angiotensin-Converting Enzyme Inhibitors; D010982:Platelet-Derived Growth Factor; D011518:Proto-Oncogene Proteins; D020574:Proto-Oncogene Proteins c-sis; D016212:Transforming Growth Factor beta; D017315:Cilazapril