Effects of haemoglobin 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 microM) 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 microM to 0.1 mM for 5-HT-constricted rings, and 0.1 microM 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.
Sikorski
B W
BW
Department of Pharmacology, Monash University, Clayton, Victoria, Australia.
Hodgson
W C
WC
King
R G
RG
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001835:Body Weight / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D006454:Hemoglobins / Q000494:pharmacology*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D019335:Nitroarginine; D009638:Norepinephrine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects*
D006454:Hemoglobins; D012702:Serotonin Antagonists; D019335:Nitroarginine; D012701:Serotonin; D001120:Arginine; D000109:Acetylcholine; D009638:Norepinephrine; D007213:Indomethacin