[Decrease of nitric oxide (NO)-cGMP-dependent vasodilatation in the vessels of lesser circulation in endothelial dysfunction].
Inducible NO-synthase inhibitor aminoguanidine (AG) was used for investigation into enhanced nitric oxide (NO) production influence on elevated pressure in the pulmonary circulation (pulmonary hypertension, PH) under endothelial dysfunction. PH was simulated by subcutaneous injection of 60 mg/kg MCT to Wistar rats. Experimental groups were given AG in drinking water (15 mg/(kg x day)), and control groups were given drinking water. Rate of nitrite/nitrate excretion (RENOx) with urine was measured. The RENOx was elevated since second week as long as through the PH development. Chronic AG administration led to RENOx and soluble guanylate cyclase (sGC) NO-dependent activity restoration, and also it led to partial restoration of the right ventricular pressure. AG administration restored the perfusion pressure responses of isolated pulmonary arteries to acetylcholine. These results suggest that chronic inducible NO-synthase inhibition restores the impaired endothelium-dependent and sGC-dependent relaxation of pulmonary artery in MC-induced PH.
Medvedeva
N A
NA
Bonartsev
A P
AP
Postnikov
A B
AB
Slavutskaia
A V
AV
D'iakonov
K B
KB
D000818:Animals; D006152:Cyclic GMP / Q000378:metabolism*; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology*; D008168:Lung / Q000098:blood supply / Q000378:metabolism; D016686:Monocrotaline / Q000494:pharmacology; D009566:Nitrates / Q000652:urine; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D052247:Nitric Oxide Synthase Type II; D009573:Nitrites / Q000652:urine; D011652:Pulmonary Circulation / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D014664:Vasodilation / Q000502:physiology*
D004791:Enzyme Inhibitors; D006146:Guanidines; D009566:Nitrates; D009573:Nitrites; D009569:Nitric Oxide; D016686:Monocrotaline; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D006152:Cyclic GMP; C004479:pimagedine