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 functional anomalies in experimentally diabetic rats, possibly via the prevention of a diabetes-induced vascular dysfunction. The acute effects of AG on endothelium-dependent relaxation of aortae in the presence of indomethacin and on pressor responses and prostacyclin release in isolated perfused lungs, were therefore investigated using tissues from control and streptozotocin-diabetic rats. Endothelium-dependent relaxations of aortae were reduced by aminoguanidine (control 20%, and diabetic 25%). For lungs, angiotensin II-induced pressor responses were unaffected by AG, whereas the nitric oxide synthase inhibitor L-NAME caused integrated pressor responses to be increased in lungs from control and diabetic rats (2.0 and 1.8 fold respectively). Individually, AG (1 mM) and L-NAME (10 microM) 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 vitro, with little effect upon endothelium-dependent vasodilatation, and secondly, that the regulation of vasodilator prostanoid release by the pulmonary circulation of the rat may be altered in experimental diabetes.
Dewhurst
M
M
Department of Pharmacology, Queen Mary and Westfield College, University of London, UK.
Stevens
E J
EJ
Tomlinson
D R
DR
D000109:Acetylcholine / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D011464:Epoprostenol / Q000378:metabolism; D006146:Guanidines / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014664:Vasodilation / Q000187:drug effects*
D004791:Enzyme Inhibitors; D006146:Guanidines; D000804:Angiotensin II; D010656:Phenylephrine; D011464:Epoprostenol; D000109:Acetylcholine; C004479:pimagedine; D019331:NG-Nitroarginine Methyl Ester