ABSTRACT
We performed correction of endothelial dysfunction with phenol derivatives KUD-259 and KUD-974 containing heteroatomic and heterocyclic structures. Pharmacological activity of KUD-259 and KUD-974 surpassed that of L-norvaline, a non-selective arginase inhibitor.
Subject(s)
Arginase/antagonists & inhibitors , Phenol/chemistry , Thrombin/chemistry , Animals , Endothelium, Vascular/drug effects , Endothelium, Vascular/metabolism , Male , NG-Nitroarginine Methyl Ester/pharmacology , Nitric Oxide/pharmacology , Rats , Rats, Wistar , Signal Transduction/drug effects , Valine/analogs & derivatives , Valine/pharmacologyABSTRACT
L-arginine (200 mg/kg), vitamin B(6) (2 mg/kg), and folic acid (0.2 mg/kg) exert a protective effect on endothelial function in L-NAME-induced NO deficiency in male and pregnant female Wistar rats. Combined administration of these agents effectively prevented the development of endothelial dysfunction and L-NAME-induced preeclampsia.
Subject(s)
Arginine/pharmacology , Endothelium/physiopathology , Folic Acid/pharmacology , Nitric Oxide/deficiency , Placenta/blood supply , Vitamin B 6/pharmacology , Animals , Arginine/therapeutic use , Drug Therapy, Combination , Endothelium/drug effects , Endothelium/metabolism , Female , Folic Acid/therapeutic use , Male , Microcirculation/drug effects , NG-Nitroarginine Methyl Ester , Nitric Oxide Synthase Type III/metabolism , Placenta/drug effects , Placenta/metabolism , Pre-Eclampsia/chemically induced , Pre-Eclampsia/drug therapy , Pre-Eclampsia/metabolism , Pregnancy , Rats , Rats, Wistar , Vitamin B 6/therapeutic useABSTRACT
Intragastric methionine (3 g/kg daily for 7 days) elevates homocysteine concentration and increases the endothelial dysfunction coefficient. This protocol of methionine treatment is an adequate model of hyperhomocysteine-induced endothelial dysfunction and can be used for studies of the endothelio- and cardioprotective effects of drugs.
Subject(s)
Endothelium, Vascular/pathology , Hyperhomocysteinemia/physiopathology , Vascular Diseases/physiopathology , Animals , Endothelium, Vascular/drug effects , Hyperhomocysteinemia/complications , Hyperhomocysteinemia/drug therapy , Methionine/therapeutic use , Rats , Vascular Diseases/drug therapy , Vascular Diseases/etiologyABSTRACT
Experimental NO deficiency induced by L-NAME injection led to the development of arterial hypertension, endothelial dysfunction, and cardiomyocyte hypertrophy and reduced blood content of nitrates and nitrites. Impaza, NO donors, activators of NO-synthase, antioxidants, and antihypertensive preparations produced endothelium-protective effect of different degree.
