Attenuated responses to endothelin‐1, KCl and CaCl₂, but not noradrenaline, of aortae from rats with streptozotocin‐induced diabetes mellitus

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. Maximum responses to ET‐1 (0.13–18 nm), KCl (2–20 mm) or CaCl₂ (10 μm–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. Responses to noradrenaline (NA, 0.1 nm‐26 μm) of aortae from STZ‐treated rats were not significantly different from responses of aortae of control rats. 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). 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. Indomethacin (5 μm) did not prevent the reduced maximum responsiveness to ET‐1 in rings from STZ‐treated rats compared with those from controls. 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. 1991 British Pharmacological Society