Intrinsic factors involved in vascular smooth muscle cell proliferation in hypertension.
The exaggerated response to growth factors of vascular smooth muscle cells from spontaneously hypertensive rats when compared to cells from normotensive control Wistar-Kyoto rats persists in culture, indicating an intrinsic/genetic defect. The time course of 3H-thymidine incorporation shows that synchronized vascular smooth muscle cells from spontaneously hypertensive rats start to synthesize new DNA earlier after mitogenic stimulation than cells from normotensive rats. Flow cytometry demonstrates that in cell populations growing in 10% calf serum for three d there is a higher proportion of cells from spontaneously hypertensive rats in the S phase of the cell cycle. The same proportions in the G2 + M phase of growing, as well as synchronized cells from normotensive and hypertensive rats indicate no difference in polyploidy. Forward light scatter analysis reveals no difference in cell size. These results suggest that the growth kinetic of vascular smooth muscle cells from normotensive and spontaneously hypertensive rats are different. Since the defect seems to be in the prereplicative phase of the cell cycle susceptible to regulation by extrinsic factors, we studied the effect of the calmodulin inhibitor, W-7, on DNA synthesis. The comparable IC50 of W-7 to inhibit cell growth of vascular smooth muscle cells of both origins indicates that the defect may not be due only to calmodulin, and furthermore suggests the involvement of a previously-reported calmodulin activator in hypertension.
Hadrava
V
V
Centre de Recherche Hôtel-Dieu de Montréal, Quebec.
Tremblay
J
J
Hamet
P
P
D000818:Animals; D002455:Cell Division; D004247:DNA / Q000096:biosynthesis; D005434:Flow Cytometry; D016193:G1 Phase; D006973:Hypertension / Q000378:metabolism / Q000473:pathology*; D007700:Kinetics; D008297:Male; D008938:Mitosis; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D016192:Resting Phase, Cell Cycle; D016196:S Phase; D013449:Sulfonamides / Q000494:pharmacology
D013449:Sulfonamides; C017967:W 7; D004247:DNA