Modulation of vasoconstrictor and dilator pancreatic metabolites in streptozotocine diabetic rats:: effect of bradykinin blockage and NO inhibition

This study was designed to investigate the effect of HOE 140 (a bradykinin beta(2) receptor antagonist) and N-W-nitro-L-arginine methyl-ester (L-NAME, a nitric oxide synthase inhibitor) on endothelial and P-tell function in induced streptozotocine (Stz) diabetic rats. The decrease in the insulinogenic index after Stz effect (control 286.03 +/- 104.12 and Stz 18.22 +/- 10.77*, *P < 0.001 vs. Control) was partially prevented by L-NAME (46.54 +/- 10.12, P < 0.001) and HOE 140 (105.12 +/- 23.06, P < 0.001). It was observed in diabetic rats: L-NAME increased the pancreatic endothelin-1 (ET-1) production and HOE 140 did not. L-NAME and HOE 140 decreased the nitric oxide (NO) synthesis, increased prostacyclin 1-2 (PGI(2)), and did not modify thromboxane A-2 (TxA(2)). These results indicate that L-NAME and HOE 140 had a protective effect on the development of diabetes in the rat. The protective effect of L-NAME and HOE 140 on the insulinogenic index could be related to ET-1, bradykinin, PGI(2), and NO. (C) 1999 Elsevier Science Inc. All rights reserved.