Effects of hypertension on migration and proliferation of smooth muscle in culture.

Abstract

SUMMARY Migratory and proliferative characteristics of explanted rat aortic smooth muscle cells were studied in response to hypertension induced by 4 weeks of deoxycorticosterone-salt administration. Under low serum conditions (0.1% fetal bovine serum), over 80% of aortic medial explants from hypertensive rats yielded smooth muscle cell colonies after 8 days of culture while fewer than 10% of the control explants were positive. Time lapse video analysis of subsequent growth in the presence of 10% serum revealed that interdivision times of smooth muscle cells from hypertensive animals were significantly shorter than those in controls (p < 0.01). Significant differences in proliferative capacity of smooth muscle cells were evident, even after one subculture (p < 0.01). Comparison of these results with data from mechanical injury suggests that 4 weeks of deoxycorticosterone-salt hypertension can potentiate subsequent smooth muscle cell migration and growth in vitro to an extent similar to that observed with the combined effects of total endothelial denudation and wall distention by a balloon catheter. N our earlier studies on the effects of hypertension on the vascular wall, we found that smooth muscle cells (SMC) and blood-borne cellular elements, together with excessive extracellular matrix, were present in the aortic intima in young rats after 4 weeks of deoxycorticosterone (DOC)-salt hypertension.1 Similar intimal changes were observed in normotensive, aged rats.2 The leukocytes originated from the circulating blood, as indicated by the positions of white cells adherent to and between endothelial cells, while the subendothelial SMC appeared to have migrated from the media. 2The present study was designed to investigate the effects of hypertension on SMC by determining migration and growth properties of the selected cells migrating out of aortic explants. We have made use of an explant test that we developed for the assessment of migration of SMC in response to dilating and denuding balloon catheter injury.-1 This assay allows the use of tissue culture methods to study proliferative and mi-

1989 Corcoran lecture: adaptive and maladaptive responses of the arterial wall to hypertension.

“…32 Platelet adherence to the intima is not typically present and neither is endothelial cell loss. We have observed increased motility of SMCs out of aortic explants obtained from hypertensive animals 38 and increased growth potential of such cells. 38 - 39 If similar changes also occur in vivo, then hypertension might stimulate medial SMCs to migrate into the intima where they could proliferate and contribute to the development of intimal thickening.…”

“…We have observed increased motility of SMCs out of aortic explants obtained from hypertensive animals 38 and increased growth potential of such cells. 38 - 39 If similar changes also occur in vivo, then hypertension might stimulate medial SMCs to migrate into the intima where they could proliferate and contribute to the development of intimal thickening. Many of the intimal changes caused by hypertension are broadly similar to those observed with aging or hypercholesterolemia.…”

Kinetic properties of the Na+/H+ antiporter of lymphocytes from the spontaneously hypertensive rat: role of intracellular pH.

“…The K., however, was similar to that of cells from the WKY rat. There is abundant evidence for accelerated growth in culture of VSMC from the SHR (9,35,36), and several studies have shown participation of the Na+/H' antiporter in the initiation of cell growth (3,4,37). It is conceivable that increased growth rate in SHR cells may require recruitment of a greater number of antiporters in the plasma membrane or enhancement oftheir activity.…”

Allograft-induced arterial wall injury and response in normotensive and spontaneously hypertensive rats.

“…Similar results have been reported for deoxycorticosterone acetate salt-induced hypertension, in which environmental conditions rather than genetics lead to an increase in smooth muscle cell proliferative potential. 37 This difference in the physiological activity of smooth muscle cells in primary and secondary hypertension could explain the greater intimal proliferation in SHRs.…”