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 microM-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 microM) 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 microM) 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, KCI 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.
Fulton
D J
DJ
Department of Pharmacology, Monash University, Clayton, Victoria, Australia.
Hodgson
W C
WC
Sikorski
B W
BW
King
R G
RG
D000818:Animals; D001013:Aorta, Thoracic / Q000033:anatomy & histology / Q000187:drug effects; D001835:Body Weight / Q000502:physiology; D002122:Calcium Chloride / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D004558:Electric Stimulation; D016232:Endothelins / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000502:physiology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology*; D009929:Organ Size / Q000502:physiology; D011189:Potassium Chloride / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D014661:Vasoconstriction / Q000187:drug effects
D016232:Endothelins; D011189:Potassium Chloride; D002122:Calcium Chloride; D009638:Norepinephrine; D007213:Indomethacin