title: Mitogenic events induced by vasopressin in aortic fibroblasts from spontaneously hypertensive rats.
abstract: 1. To further explore the mechanisms of arterial growth, we investigated the signalling pathways through which arginine-vasopressin acts as a mitogen in cultured adventitial aortic fibroblasts of the spontaneously hypertensive rat, and we examined the mechanisms involved in the hyperresponsiveness to arginine-vasopressin of fibroblasts from spontaneously hypertensive rats compared with fibroblasts from Wistar-Kyoto rats. 2. Arginine-vasopressin-induced [3H]thymidine incorporation was used to determine the peptide mitogenicity. Arginine-vasopressin-triggered hydrolysis of phosphoinositides by phospholipase C was evaluated by measuring [3H]inositol phosphate formation. The role of protein kinase C and protein tyrosine kinases in arginine-vasopressin mitogenicity was assessed by stimulating the cells with arginine-vasopressin in the presence of 12-O-tetradecanoylphorbol 13-acetate and tyrphostin (a tyrosine kinase inhibitor), respectively. 3. Arginine-vasopressin-induced DNA synthesis was completely abolished in confluent cells, whereas [3H]inositol phosphate formation was only reduced. The presence of 12-O-tetradecanoylphorbol 13-acetate markedly decreased arginine-vasopressin-induced [3H]thymidine incorporation in fibroblasts from spontaneously hypertensive rats and was without effect in fibroblasts from Wistar-Kyoto rats. Tyrphostin abolished arginine-vasopressin-induced [3H]thymidine incorporation in a dose-dependent manner and did not affect the formation of inositol phosphates. 4. These results indicate that phospholipase C activation is not sufficient for arginine-vasopressin-induced mitogenesis. They also suggest that (i) tyrosine kinase activation is a necessary step in the transduction of the arginine-vasopressin mitogenic signal, and (ii) protein kinase C participates in the increased mitogenic potency of arginine-vasopressin in spontaneously hypertensive rats.
authors.affiliation: CNRS URA 1482, Université René Descartes, Paris, France.
authors.forename: D L
authors.initials: DL
authors.lastname: Zhu
authors.forename: T
authors.initials: T
authors.lastname: Herembert
authors.forename: P
authors.initials: P
authors.lastname: Marche
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism* / Q000473:pathology; D001127:Arginine Vasopressin / Q000502:physiology*; D002455:Cell Division; D002478:Cells, Cultured; D005347:Fibroblasts / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D006133:Growth Substances / Q000502:physiology*; D006973:Hypertension / Q000378:metabolism* / Q000473:pathology; D008297:Male; D011493:Protein Kinase C / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D015398:Signal Transduction; D013936:Thymidine / Q000378:metabolism; D010738:Type C Phospholipases / Q000378:metabolism
chemical_list: D006133:Growth Substances; D001127:Arginine Vasopressin; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C; D010738:Type C Phospholipases; D013936:Thymidine