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-sized arteries has not already been demonstrated, we examined the effect of growth factors on secreted and membrane-bound PG synthesis by cultured mesenteric vascular smooth muscle cells (VSMC) from spontaneously hypertensive rats (SHR) and Wistar rats. After 48 hours of stimulation with angiotensin II (Ang II), platelet-derived growth factor (PDGF-BB), and 10% fetal calf serum (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 label method with both [(3)H]-glucosamine and [(35)S]-sodium sulfate, which are incorporated into all complex carbohydrates or only into sulfated disaccharides, respectively. VSMC from SHR displayed a significantly lower level of synthesis of M-ECM [(3)H]-PGs than those of Wistar rats in all the experimental groups, including the control group (0. 1% FCS), but no differences in M-ECM [(35)S] uptake were found in any case. In the P-ECM, Ang II was the only factor that produced a lesser effect on [(3)H]-glucosamine and a greater effect on [(35)S]-sodium sulfate uptakes in VSMC from SHR than from Wistar rats. The most prominent change seen in VSMC from SHR was an increased sulfation, assessed by [(35)S]/[(3)H] ratio, in nonstimulated cells and in response to 10% FCS and Ang II but not to PDGF-BB compared with VSMC from Wistar rats. These data indicate the existence of changes in PG modulation in the resistance vessels of SHR, which suggests that PGs may contribute to the development of structural and functional modifications in hypertensive states.
Castro
C M
CM
Laboratory of Cell Culture, School of Medicine-Universidad Nacional de Cuyo, Mendoza, Argentina.
Cruzado
M C
MC
Miatello
R M
RM
Risler
N R
NR
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D000077214:Becaplermin; D002478:Cells, Cultured; D006973:Hypertension / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D008638:Mesenteric Arteries / Q000378:metabolism / Q000503:physiopathology; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000503:physiopathology; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D011509:Proteoglycans / Q000096:biosynthesis*; D020574:Proto-Oncogene Proteins c-sis; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D014655:Vascular Resistance / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D010982:Platelet-Derived Growth Factor; D011509:Proteoglycans; D020574:Proto-Oncogene Proteins c-sis; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D000077214:Becaplermin