[Molecular mechanisms controlling the proliferation of aortic smooth muscle cells in spontaneously hypertensive rats].
In order to define the molecular mechanisms involved in the hypertrophy of the arterial walls observed in essential hypertension, vascular smooth muscle cells were isolated from aortas of spontaneously hypertensive (SHR) and control (WKY) rats, and cultured (until the 4th sub-culture) in the presence of growth factors (foetal calf serum: FCS) and various vasoactive drugs. Growth rate was determined by cell counting and measurement of nuclear thymidine incorporation, and activation of phospholipase C by measurement of the inositol phosphates formed from preincorporated tritiated myo-inositol; the expression of the cellular oncogenes, c-fos and c-myc was visualized by hybridization of Northern blots performed from total RNA. In the presence of low concentrations of FCS (2 p. 100, 5 p. 100) angiotensin II (10(-7)M) and bradykinin (3 X 10(-6)M) increase the growth of both kind of cells. The inositol phosphate formation and the expression of c-fos and c-myc are also dose-dependently stimulated by these vasoactive drugs, and the cultures from SHR are more responsive than those from WKY rats. Phospholipase C hyperreactivity therefore appears to be involved in the increased proliferative ability of vascular smooth muscle cells from SHR. However other molecular processes may be involved, as suggested by the growth inhibition exerted by heparin without any action on PLC activity.
Paquet
J L
JL
INSERM U 7, hôpital Necker, Paris.
Baudouin-Legros
M
M
Meyer
P
P
D000818:Animals; D002455:Cell Division; D002478:Cells, Cultured; D006133:Growth Substances / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000502:physiology; D051381:Rats; D011918:Rats, Inbred SHR; D011919:Rats, Inbred Strains; D010738:Type C Phospholipases / Q000502:physiology*
D006133:Growth Substances; D010738:Type C Phospholipases
Mécanismes moléculaires contrôlant la prolifération des cellules musculaires lisses aortiques de SHR.