Characteristics of impaired endothelium-dependent relaxation of rat aorta after streptozotocin-induced diabetes

AIM: To study whether impaired endothelium-dependent relaxation (EDR) in ea rly diabetic mellitus in response to different receptor-mediated and nonrec eptor-mediated vasodilators ran parallel and its possible mechanism. METHOD S: Isometric tension recording in aortic rings from streptozotocin (Str)ind uced diabetic and age-matched nondiabetic rats. RESULTS: EDR induced by rec eptor agonist acetylcholine (ACh), histamine (His) or bradykinin (BK) were all significantly reduced in diabetic rings compared with control rings, wh ereas nonreceptor agonist calcimycin-induced EDR was well reserved in diabe tic rings [IC50 control: (0.13 +/- 0.7) mu mol L-1 diabetic: (0.14 +/- 0.06 ) mu mol.L-1, P > 0.05, n = 7]. Cyclopiazonic acid (CPA) which also is a no nreceptor mediated endothelium-dependent vasorelaxant and cells' capacitati ve Ca2+ entry stimulant, failed to trigger EDR in diabetic rings. Pretreatm ent with N-w-nitro-L-arginine methylester;( L-NAME, 0.3 mmol L-1) not only abolished all of the EDR elicited by above mentioned vasodilators in either of diabetic or control rings, but also leveled responses triggered by each of the agonists between diabetic and control rings. Upon the maximal. EDR induced by ACh (1 mol L-1) or CPA (3. mu mol.L-1) in phenylephrine (1 mu mo l L-1) precontracted rings, calcimycin (1 mu mol.L-1) further relaxed diabe tic rings, but contracted control preparations. When endothelium was denude d, relaxation evoked by sodium nitroprusside and contractions triggered by CPA or His were all identical between diabetic and control rings. CONCLUSIO N: Receptor agonists but not nonreceptor agonists-induced EDR are commonly impaired in 4-wk Str-induced diabetic rat aorta, and this defective effect is attributable to the low formation of EDRF/NO which is related to impaire d capacitative Ca2+ entry pathway in endothelium.