ATTENUATED RESPONSES TO ENDOTHELIN-1, KCL AND CACL2, BUT NOT NORADRENALINE, OF AORTAE FROM RATS WITH STREPTOZOTOCIN-INDUCED DIABETES-MELLITUS

1 This study investigated the responsiveness to vasoconstrictor agents (including endothelin-1, ET-1) of aortic rings from rats with two-week streptozotocin (STZ, 60 mg kg-1, i.v.)-induced diabetes and vehicle-treated control rats. The basal tension was 10 g, which was estimated to be more physiological than the tension of 1-2 g that has been previously used for most studies of aortic rings from diabetic rats. 2 Maximum responses to ET-1 (0.13-18 nM), KCl (2-20 mM) or CaCl2 (10-mu-M-10 mM) were reduced in aortae from STZ-treated rats compared to those from control rats. Such reductions were still evident after removal of the endothelium. 3 Responses to noradrenaline (NA, 0.1 nM-26-mu-M) of aortae from STZ-treated rats were not significantly different from responses of aortae of control rats. 4 Removal of endothelium resulted in a significant reduction in the EC50 values for NA of rings from both STZ-treated rats (6.90 +/- 0.13 and 8.17 +/- 0.35 (-log M) with and without endothelium, respectively, n = 5) and control rats (6.90 +/- 0.15 and 8.37 +/- 0.44 (-log M) with and without endothelium, respectively, n = 5). 5 In calcium-free medium (with 1 mM EGTA), responses to NA and ET-1 were reduced compared with those in normal Krebs solution and maximum responses were less in rings from STZ-treated compared with control rats. 6 Indomethacin (5-mu-M) did not prevent the reduced maximum responsiveness to ET-1 in rings from STZ-treated rats compared with those from controls. 7 This study indicates that changes in vascular responsiveness to ET-1, KCl and CaCl2 (but not NA) occur in aortae of two-week STZ-treated rats. The endothelium does not appear to play a major role in mediating changes in responsiveness to ET-1.