INSULIN IS REQUIRED FOR ANGIOTENSIN II-MEDIATED HYPERTROPHY OF SMOOTH-MUSCLE CELLS

The prevalence of hypertension and atherosclerosis among subjects with hyperinsulinemia supports the premise of a direct metabolic link betw een insulin and angiotensin II at the cellular level. In the present s tudy, the effect of insulin on the angiotensin II-induced growth of A1 0 smooth muscle cells (SMC) was investigated. Treatment of quiescent A 10 cells with angiotensin II caused an increase in RNA synthesis, prot o-oncogene c-fos mRNA levels and cell size dependent upon pretreatment with insulin. The insulin requirement was independent of its actions as a growth factor, since a pre-treatment of al least 24 h with insuli n was essential for growth stimulation by angiotensin II. Using RT-PCR , insulin was shown to regulate AT(2) receptor expression in both quie scent and differentiating cells. These data suggest the AT(2) receptor , which mediates the growth effects of angiotensin II in A10 cells, ma y be the critical target for the effect of insulin.