Proteoglycan production by vascular smooth muscle cells from resistance arteries of hypertensive rats

Extracellular matrix (ECM) modifications in the vascular wall contribute to the narrowing of arteries in hypertension. Because direct evidence for the role of proteoglycans (PGs) in the pathological process of resistance-size d arteries has not already been demonstrated, we examined the effect of gro wth factors on secreted and membrane-bound PG synthesis by cultured mesente ric vascular smooth muscle cells (VSMC) from spontaneously hypertensive rat s (SHR) and Wister rats. After 48 hours of stimulation with angiotensin II (Ang II), platelet-derived growth factor (PDGF-BB), and 10% fetal calf seru m (FCS) or 0.1% FCS as control, PG synthesis (in dpm/ng DNA) was evaluated in the medium (M-ECM) and in the cell layer (P-ECM) by a double-isotopic la bel method with both [H-3]-glucosamine and [S-35]-sodium sulfate, which are incorporated into all complex carbohydrates or only into sulfated disaccha rides, respectively. VSMC from SHR displayed a significantly lower level of synthesis of M-ECM [H-3]-PGs than those of Wistar rats in all the experime ntal groups, including the control group (0.1% FCS), but no differences in M-ECM [S-35] uptake were found in any case. In the P-ECM, Ang II was the on ly factor that produced a lesser effect on [H-3]-glucosamine and a greater effect on [S-35]-sodium sulfate uptakes in VSMC from SHR than from Wistar r ats. The most prominent change seen in VSMC from SHR was an increased sulfa tion, assessed by [S-35]/[H-3] ratio, in nonstimulated cells and in respons e to 10% FCS and Ang II but not to PDGF-BB compared with VSMC from Wistar r ats. These data indicate the existence of changes in PG modulation in the r esistance vessels of SHR, which suggests that PGs may contribute to the dev elopment of structural and functional modifications in hypertensive states.