[Effect of chronic administration of aminoguanidine on the reactivity of pulmonary vessels in rats with monocrotaline-induced pulmonary hypertension].
Monocrotaline (MCT)-induced pulmonary hepertension (PH) is associated with impaired endothelium-dependent relaxation and increased activity of inducible NO-synthase (iNOS). To examine the role of iNOS in MCT-induced PH, we used iNOS inhibitor: aminoguanidine (AG). The PH was simulated with a subcutaneous injection of 60 mg/kg MCT to Wistar rats; control rats were injected with saline. Then each group was separated into 2 subgroups: the 1st one was given drinking water (MCT-C and C-C groups) whereas the 2nd one was given AG in drinking water (15 mg/(kg(-1) x day(-1)) (MCT-AG and C-AG groups). In 4 weeks, the perfusion pressure (PP) responses of isolated pulmonary arteries to acetylcholine (Ach) and activator of soluble guanylate cyclase (sGC), FPTO, were examined. In the MCT-C group, a decrease of relative PP to perfusion of 1 x 10(-8) M and 5 x 10(-8) M Ach and 1 x 10(-8) M FPTO was diminished. This reduction of relaxant responses in MCT-treated rats was prevented by AG treatment. The findings suggest that AG administration restores the impaired endothelium-dependent and sGC-dependent relaxation of the pulmonary artery at MCT-induced PH.
A P
AP
Bonartsev
A v
Av
Slavutskaia
A B
AB
Postnikov
N A
NA
Medvedeva
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D004730:Endothelium, Vascular / Q000187:drug effects; D006146:Guanidines / Q000008:administration & dosage / Q000494:pharmacology*; D006162:Guanylate Cyclase; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000503:physiopathology*; D017380:Hypertrophy, Right Ventricular / Q000503:physiopathology; D008168:Lung / Q000098:blood supply; D016686:Monocrotaline / Q000633:toxicity; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000502:physiology*; D052247:Nitric Oxide Synthase Type II; D011651:Pulmonary Artery / Q000166:cytology / Q000187:drug effects / Q000503:physiopathology*; D011652:Pulmonary Circulation / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists; D000071756:Soluble Guanylyl Cyclase
D006146:Guanidines; D018160:Receptors, Cytoplasmic and Nuclear; D016686:Monocrotaline; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D006162:Guanylate Cyclase; D000071756:Soluble Guanylyl Cyclase; D000109:Acetylcholine; C004479:pimagedine