The angiotensin I-converting enzyme inhibitor, cilazapril inhibits the platelet-derived growth factor B chain expression in glomeruli of spontaneously hypertensive rats

Ren Physiol Biochem. 1995 Sep-Oct;18(5):237-45. doi: 10.1159/000173921.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin-Converting Enzyme Inhibitors / pharmacology*
  • Animals
  • Blood Pressure / drug effects
  • Cilazapril / pharmacology*
  • Heart Rate / drug effects
  • Hypertension / metabolism*
  • Hypertension / pathology
  • Kidney Glomerulus / metabolism*
  • Kidney Glomerulus / pathology
  • Platelet-Derived Growth Factor / antagonists & inhibitors*
  • Platelet-Derived Growth Factor / metabolism
  • Proto-Oncogene Proteins / antagonists & inhibitors*
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-sis
  • Rats
  • Rats, Inbred SHR / metabolism*
  • Rats, Inbred WKY
  • Reference Values
  • Transforming Growth Factor beta / metabolism

Substances

  • Angiotensin-Converting Enzyme Inhibitors
  • Platelet-Derived Growth Factor
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-sis
  • Transforming Growth Factor beta
  • Cilazapril