EFFECTS OF HEMOGLOBIN AND N-NITRO-L-ARGININE ON CONSTRICTOR AND DILATOR RESPONSES OF AORTIC RINGS FROM STREPTOZOTOCIN-DIABETIC RATS

This study investigated the effects of N-nitro-L-arginine and haemoglobin on responses of aortic rings (10 g resting tension) from 2-week streptozotocin-diabetic and control rats. N-Nitro-L-arginine (0.1 mM) or haemoglobin (10 muM) potentiated constrictor responses of aortae from both groups of rats to 5-hydroxytryptamine (5-HT) or noradrenaline. They also overcame the tachyphylaxis which occurred on the second exposure to 5-HT. Following constriction of aortae with 5-HT or noradrenaline, acetylcholine produced concentration-dependent relaxation. At concentrations of acetylcholine of 0.1 muM to 0.1 mM for 5-HT-constricted rings, and 0.1 muM for noradrenaline-constricted rings, the specific component of relaxation attributable to acetylcholine was significantly less for aortae from diabetic rats than for those from controls. For aortae from both groups, N-nitro-L-arginine (or haemoglobin) inhibited relaxation in the presence of acetylcholine (noradrenaline or 5-HT-constricted rings), and N-nitro-L-arginine (or N-nitro-L-arginine with haemoglobin) partially inhibited spontaneous relaxation of 5-HT-constricted rings. These results suggest that NO may play a role in tachyphylaxis to 5-HT, and that acetylcholine-induced output of endothelium-derived relaxing factor/nitric oxide (EDRF/NO) (or responsiveness to EDRF/NO) may be reduced in noradrenaline- and 5-HT-constricted aortic rings from 2-week diabetic rats.