DECREASE OF BRADYKININ-INDUCED GLOMERULAR CONTRACTION IN DIABETIC RAT- A NEW CELLULAR INTERPRETATION

The contractile response to bradykinin (BK), measured by the reduction of the planar surface area, was studied in glomeruli and mesangial ce lls (MC) isolated from diabetic rats (D) one week after diabetes induc tion,vith injection of streptozotocin (STZ; 60 mg kg(-1), i.p.). Resul ts were compared with age and weight-matched untreated rats (N) and we re expressed by two parameters of cell activity, the mean maximum cont raction (MMC) and the proportion of contractile cells (PCC). Glomerula r and mesangial contraction were found to be clearly reduced in diabet ic rats in response to 100 nM BK. The lower contractile response was a ssociated with a decrease of both glomerular calcium uptake and mesang ial cell intracellular calcium mobilization. The fact that cell pretre atment with two protein kinase C (PKC) inhibitors, phorbol 12-13 myris tate acetate and calphostin, lowered normal cell contraction at the le vel of that found in diabetic MC,without any significant effect in the latter, suggests the involvement of a PKC pathway, perhaps by a decre ase of activatable PKC in diabetes. In addition, our results led to th e first description of a possible role of the kallikrein-kinin system in the early glomerular hemodynamic changes occurring in diabetes. Ins ulin (1-200 nM) increased the contractile response of cultured diabeti c cells (MMC), and in this case, it also increased the PCC. It must be stressed that the effect of 1 nM insulin on the former (88 % increase ) was very much smaller than its effect on the latter (103 % increase) . The combination of the two parameters (contraction index, CI) provid ed a realistic evaluation of the contractile capacities of the cell po pulation of the cultures as a whole. The differences in this index bet ween normal and diabetic cell populations, in the absence or presence of insulin, were strictly parallel to those found in intact glomeruli. Finally; our results further confirm (Ouardani ct al., Biol. Cell 86, 127, (1996)) the limit of the first five cell passages within which c ultured MC can be reasonably used for tile study of contractile abnorm alities occurring in the early steps of diabetic state.