[Study of mechanisms responsible for hyperproliferation of aortic cells in spontaneously hypertensive rats].
In order to determine the mechanisms which could be responsible for the hypertrophy of vascular wall associated with primary hypertension, we have investigated the mechanisms involved in the proliferation of aortic cells from spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) controls. In this study we have examined the role of phospholipase C which is responsible for the formation of second messengers, the function of protein kinase C and that of GTP-binding proteins (G proteins) which couple membrane receptors to phospholipase C. The adventitial fibroblasts from thoracic aorta were chosen as cell model in culture. The capacity of proliferation in response to 10% serum was analyzed by cell number determination and by measuring the incorporation of 3H-thymidine into newly synthesized DNA. Our results showed that SHR-derived fibroblasts proliferated more rapidly and incorporated more 3H-thymidine than WKY-derived fibroblasts. However, the phospholipase C activity, measured by the serum-stimulated production of 3H-inositol phosphates in cells prelabeled with 3H-inositol, did not differ between SHR- and WKY-derived cells. The desensitization of protein kinase C, by long term (2 d) treatment with high dose (300 nM) of phorbol 12-myristate, 13-acetate (TPA), markedly augmented, but to the same extent, the 3H-thymidine incorporation into DNA of SHR- and WKY-derived fibroblasts. Moreover, protein kinase C activation by TPA caused a parallel reduction (25-30%) of the incorporation of 3H-thymidine into DNA of SHR- and WKY-derived cells. Under the same experimental conditions, the growth of SHR- and WKY-derived fibroblasts was reduced by TPA in a dose-dependent manner (up to 20%) to the same extent.(ABSTRACT TRUNCATED AT 250 WORDS)
Zhu
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DL
Groupe INSERM de pharmacologie vasculaire, hôpital Necker, Paris.
Herembert
T
T
Marche
P
P
D000818:Animals; D001011:Aorta; D005347:Fibroblasts / Q000201:enzymology / Q000473:pathology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000503:physiopathology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D010738:Type C Phospholipases / Q000378:metabolism
C029152:G-substrate; D009419:Nerve Tissue Proteins; D011493:Protein Kinase C; D010738:Type C Phospholipases
Etude des mécanismes impliqués dans l'hyperprolifération des cellules aortiques du rat génétiquement hypertendu.