Enhanced Proliferating Activity of Cultured Smooth Muscle Cells From SHR

In order to explore the cellular mechanisms responsible for the vascular abnormalities observed in hypertension, smooth muscle cells (SMC) were cultured after enzymatic digestion of aortas from both normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). These cultures were performed in the presence of fetal calf serum (FCS) and stimulated by vasoactive agents (angiotension II, serotonin, bradykinin). Growth rate was determined by cell counting and measurement of nuclear-tritiated thymidine incorporation and phospholipase C (PLC) activation by measurement of 3h-inositol mono-, di-, tri-, and tetra-phosphates formed from preincorporated 3h-myo-inositol. Cells from SHR proliferate more actively than control ones in the presence of 10% FCS but don't significantly differ at lower concentrations. In the presence of 5% FCS angiotensin II (10(-7) mol/L), 5-HT (10(-6) mol/L) and bradykinin (10(-6) mol/L) enhance cell proliferation and their effect is more important in cultures from SHR. The phospholipase C activation induced by these drugs was also more important in these SHR cultures than in control ones. The PLC hyperreactivity observed in SHR cells may therefore be involved in their enhanced proliferating activity evidenced in culture and in the vascular abnormalities described in vivo.