M. Ouardani et al., DECREASE OF BRADYKININ-INDUCED GLOMERULAR CONTRACTION IN DIABETIC RAT- A NEW CELLULAR INTERPRETATION, European journal of cell biology, 73(3), 1997, pp. 232-239
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.