Is the regulation of apoptosis altered in smooth muscle cells of adult spontaneously hypertensive rats?

Hypertension. 1997 Mar;29(3):776-80. doi: 10.1161/01.hyp.29.3.776.

Abstract

Whereas the protein product of the Bcl-2 gene inhibits apoptosis, the protein product of the Bax gene acts as a promoter of apoptosis. To gain insight into the regulation of apoptosis in vascular smooth muscle cells in arterial hypertension, we investigated the expression of the proteins Bcl-2 and Bax in small intramyocardial arteries of 36-week-old normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). In addition, 16-week-old SHR were treated for 20 weeks with the angiotensin-converting enzyme inhibitor quinapril and killed at 36 weeks of age. We measured the percentages of smooth muscle cells expressing these proteins using monoclonal antibodies and the avidin-biotin immunoperoxidase method. Compared with WKY, untreated SHR exhibited increased (P<.001) Bcl-2 expression and similar Bax expression. Values of Bcl-2 measured in quinapril-treated SHR were significantly lower than values measured in untreated SHR and similar to values measured in WKY. Quinapril-treated SHR showed higher (P<.001) Bax expression than WKY and untreated SHR. Bcl-2 expression was directly correlated with systolic pressure. Inverse correlations were found between the expression of Bax and the activities of both cardiac and circulating angiotensin-converting enzyme. These findings suggest that smooth muscle cell apoptosis might be inhibited in small arteries of adult SHR as a consequence of an excess of the protein Bcl-2. In addition, our results suggest that chronic angiotensin-converting enzyme inhibition might restore the susceptibility to apoptosis in these cells through stimulation of the protein Bax.

Publication types

  • Comparative Study

MeSH terms

  • Angiotensin-Converting Enzyme Inhibitors / pharmacology*
  • Animals
  • Apoptosis / drug effects
  • Apoptosis / genetics*
  • Genes, bcl-2 / physiology*
  • Hypertension / metabolism*
  • Isoquinolines / pharmacology*
  • Muscle, Smooth, Vascular / drug effects*
  • Muscle, Smooth, Vascular / pathology*
  • Quinapril
  • Rats
  • Rats, Inbred SHR
  • Rats, Inbred WKY
  • Reproducibility of Results
  • Species Specificity
  • Tetrahydroisoquinolines*

Substances

  • Angiotensin-Converting Enzyme Inhibitors
  • Isoquinolines
  • Tetrahydroisoquinolines
  • Quinapril