ADENOSINE INHIBITORY EFFECT ON ENHANCED GROWTH OF AORTIC SMOOTH-MUSCLE CELLS FROM STREPTOZOTOCIN-INDUCED DIABETIC RATS

1 There is evidence to suggest that adenosine may regulate arterial sm ooth muscle cell (SMC) growth and proliferation, which is a key event in atherogenesis. This regulation may be mediated via adenylate cyclas e. As diabetes is a known risk factor for atherosclerosis, we investig ated the growth of aortic SMC from diabetic rats in primary culture an d their sensitivity to adenosine and to adenylate cyclase activity. 2 Diabetes was induced with streptozotocin (STZ, 66 mg kg(-1), i.p.) Aor tic SMC primary cultures were prepared from STZ-diabetic and age-match ed rats 5 weeks after the STZ injection. 3 SMC from STZ-diabetic rats grew faster and reached greater densities at confluence than those fro m non-diabetic animals. 4 Adenosine inhibited growth in both control a nd diabetic SMC. However, cells from STZ-diabetic rats were apparently more sensitive to adenosine. 5 Direct activation of adenylate cyclase by forskolin induced a dose-dependent growth inhibition, similar in b oth groups of cells. 6 Cholera toxin, an activator of stimulatory GTP- binding protein (G(s)), induced a similar growth inhibitory response i n non-diabetic and diabetic SMC. Pertussis toxin (PTX), an inactivator of inhibitory GTP-binding protein (G(i)), did not itself affect SMC g rowth. However, PTX increased dose-dependently the growth inhibition i nduced by adenosine in SMC from non-diabetic rats but not in SMC from diabetic rats. 7 These findings suggest a functional abnormality in G( i) activity in SMC from diabetic rats, that would explain the increase d sensitivity to the nucleoside. This impaired inhibitory pathway may reflect changes in the growth regulation of SMC in experimental diabet ic states.