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 beta2 receptor antagonist) and N(w)-nitro-L-arginine methyl-ester (L-NAME, a nitric oxide synthase inhibitor) on endothelial and beta-cell 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 (PGI2), and did not modify thromboxane A-2 (TxA2). 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, PGI2, and NO.
Ortiz
M A
MA
Department of Endocrinology, Hospital Santa Creu i Sant Pau, Barcelona, Spain.
Roselló
J
J
Xaus
C
C
Peralta
C
C
Mato
E
E
Pou
J M
JM
D000818:Animals; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology; D065168:Bradykinin Receptor Antagonists; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000503:physiopathology; D016232:Endothelins / Q000096:biosynthesis; D004791:Enzyme Inhibitors / Q000494:pharmacology; D011464:Epoprostenol / Q000096:biosynthesis; D007328:Insulin / Q000096:biosynthesis; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors*; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D043782:Receptor, Bradykinin B2; D013311:Streptozocin; D013928:Thromboxane A2 / Q000096:biosynthesis; D014661:Vasoconstriction; D014664:Vasodilation
D065168:Bradykinin Receptor Antagonists; D016232:Endothelins; D004791:Enzyme Inhibitors; D007328:Insulin; D043782:Receptor, Bradykinin B2; D009569:Nitric Oxide; D013928:Thromboxane A2; D013311:Streptozocin; C065679:icatibant; D011464:Epoprostenol; D001920:Bradykinin; D019331:NG-Nitroarginine Methyl Ester