Increased proliferation of adventitial fibroblasts from spontaneously hypertensive rat aorta.

By using aortic adventitial fibroblasts in culture as a model, we first demonstrated that cells derived from spontaneously hypertensive rats (SHR), when compared with Wistar-Kyoto (WKY)-derived cells, possessed an increased capacity to proliferate and to synthesize DNA in response to vasoactive agents. At this early stage of culture, SHR fibroblasts exhibited a higher specific growth rate. Then, to gain insight into the mechanisms which could be responsible for the difference observed, signalling pathways involved in the transduction of the mitogenic signal were analysed in cells cultured for 3 days. Results indicated that, in SHR-derived fibroblasts, an increased phospholipase C activity could account for the higher mitogenic response to thrombin or vasopressin. However, this enzymatic activity, which did not differ when fibroblasts from the two rat strains were stimulated by serum, could not be responsible for the enhanced proliferation rate of SHR-derived cells. Moreover, neither protein kinase C nor pertussis toxin-sensitive G proteins appeared to contribute to the hyperresponsiveness exhibited by SHR fibroblasts. Our results indicate that the mechanism(s) responsible for such a difference vary according to the stimulus; they also suggest that adventitial fibroblasts may participate in the modified reactivity of vascular wall associated with hypertension.