EFFECTS OF AMINOGUANIDINE AND N-G-NITRO-L-ARGININE METHYL-ESTER ON VASCULAR-RESPONSES OF AORTAE AND LUNGS FROM STREPTOZOTOCIN-DIABETIC RATS

Aminoguanidine (AG) treatment can prevent the development of some func tional anomalies in experimentally diabetic rats, possibly via the pre vention of a diabetes-induced vascular dysfunction. The acute effects of AG on endothelium-dependent relaxation of aortae in the presence of indomethacin and on presser responses and prostacyclin release in iso lated perfused lungs, were therefore investigated using tissues from c ontrol and streptozotocin-diabetic rats. Endothelium-dependent relaxat ions of aortae were reduced by aminoguanidine (control 20%, and diabet ic 25%). For lungs, angiotensin II-induced presser responses were unaf fected by AG, whereas the nitric oxide synthase inhibitor L-NAME cause d integrated presser responses to be increased in lungs from control a nd diabetic rats (2.0 and 1.8 fold respectively). Individually, AG (1 mM) and L-NAME (10 mu M) did not affect total cumulative prostacyclin release by control lungs, whereas significant increases for both were observed for diabetic lungs. In summary, these studies firstly provide evidence that AG can increase prostacyclin release from tissues in vi tro, with little effect upon endothelium-dependent vasodilatation, and secondly, that the regulation of vasodilator prostanoid release by th e pulmonary circulation of the rat may be altered in experimental diab etes.