Characteristics of Cultured Smooth Muscle Cells from the Aorta of Spontaneously Hypertensive Rats (SHR)

Abstract

SHR is a suitable model for human essential hypertension. Stroke-prone SHR (SHRSP) separated from SHR develop severe hypertension and over 95% of them die of stroke under normal dietary condition. However, they develop hypercholesteroremia and ring like fat deposition in small arteries when fed on a high fat cholesterol diet for 2-3 weeks. Many results suppose that development of hypertension and stroke in these models results from the interaction of genetic and environmental factors. It might contribute greatly to prevention of hypertensive diseases that genetic phenotypes related with them can be predicted.As environmental factors can be controlled in cell cultured system, characteristics of cultured smooth muscle cells from the aorta of SHRSP, SHRSR and Wistar-Kyoto rats (WKY) were examined. Activity of cellular proliferation were increased in SMC of SHRSP and SHRSR than that of WKY and doubling time was shortened in those of SHRSP and SHRSR. SMC from SHRSR and SHRSP showed greater Na+ influx and K+ efflux than that from WKY under 1mM ouabain treatment. Calcium antagonist, diltiazem, reduced [3H] thymidine incorporation in SMC significantly so that the strain difference in the proliferative activity disappeared completely. There was no obvious effect of diltiazem on sodium influx after blocking Na+, K+-ATPase with 1mM ouabain. This result indicates that the effect of diltiazem on sodium influx into the cells, but rather due to its direct effect on Ca influx.The strain difference in the proliferative activity is partly due to difference in transferable rate from Gl stage to S stage of cell cycle. SMC utilize various amino acids when they proliferate. A larger amount of arginine was consumed and formated ornithine in SMC of SHRSP compared to that of WKY. Also, SMC of SHRSP showed abnormalities in lipid metabolism and increased lipid incorporation. These results may contribute to the cellular mechanisms of hypertension and related diseases.