Document Detail

The effect of N-acetylcysteine and melatonin in adult spontaneously hypertensive rats with established hypertension.
MedLine Citation:
PMID:  17321519     Owner:  NLM     Status:  MEDLINE    
The attenuated nitric oxide (NO) formation and/or elevated production of reactive oxygen species are often found in experimental and human hypertension. We aimed to determine possible effects of N-acetylcysteine (1.5 g/kg/day) and N-acetyl-5-methoxytryptamine (melatonin, 10 mg/kg/day) in adult spontaneously hypertensive rats (SHR) with established hypertension. After a six-week-treatment, blood pressure was measured and NO synthase (NOS) activity, concentration of conjugated dienes, protein expression of endothelial NOS, inducible NOS and nuclear factor-kappaB (NF-kappaB) in the left ventricle were determined. Both treatments improved the NO pathway by means of enhanced NOS activity and reduced reactive oxygen species level as indicated by decreased conjugated diene concentrations and lowered NF-kappaB expression. N-acetylcysteine (but not melatonin) also increased the endothelial NOS protein expression. However, only melatonin was able to reduce blood pressure significantly. Subsequent in vitro study revealed that both N-acetylcysteine and melatonin lowered the tone of phenylephrine-precontracted femoral artery via NO-dependent relaxation. Nevertheless, melatonin-induced relaxation also involved NO-independent component which was preserved even after the blockade of soluble guanylate cyclase by oxadiazolo[4,3-a]quinoxalin-1-one. In conclusion, both N-acetylcysteine and melatonin were able to improve the NO/reactive oxygen species balance in adult SHR, but blood pressure was significantly lowered by melatonin only. This implies that a partial restoration of NO/reactive oxygen species balance achieved by the antioxidants such as N-acetylcysteine has no therapeutic effect in adult rats with established hypertension. The observed antihypertensive effect of melatonin is thus mediated by additional mechanisms independent of NO pathway.
Olga Pechánová; Josef Zicha; Ludovít Paulis; Woineshet Zenebe; Zdenka Dobesová; Stanislava Kojsová; Lýdia Jendeková; Martina Sládková; Ima Dovinová; Fedor Simko; Jaroslav Kunes
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-02-01
Journal Detail:
Title:  European journal of pharmacology     Volume:  561     ISSN:  0014-2999     ISO Abbreviation:  Eur. J. Pharmacol.     Publication Date:  2007 Apr 
Date Detail:
Created Date:  2007-03-26     Completed Date:  2007-05-22     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  1254354     Medline TA:  Eur J Pharmacol     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  129-36     Citation Subset:  IM    
Institute of Normal and Pathological Physiology, Slovak Academy of Sciences, Bratislava, Slovak Republic.
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MeSH Terms
Acetylcysteine / pharmacology*,  therapeutic use
Antioxidants / pharmacology*,  therapeutic use
Blood Pressure / drug effects
Blotting, Western
Free Radical Scavengers / pharmacology*,  therapeutic use
Hypertension / drug therapy*
Melatonin / pharmacology*,  therapeutic use
NF-kappa B / drug effects,  metabolism
Nitric Oxide / biosynthesis
Nitric Oxide Synthase / drug effects,  metabolism
Nitric Oxide Synthase Type II / drug effects,  metabolism
Nitric Oxide Synthase Type III / drug effects,  metabolism
Rats, Inbred SHR
Rats, Inbred WKY
Reactive Oxygen Species / metabolism
Vasoconstriction / drug effects
Reg. No./Substance:
0/Alkadienes; 0/Antioxidants; 0/Free Radical Scavengers; 0/NF-kappa B; 0/Reactive Oxygen Species; 10102-43-9/Nitric Oxide; 616-91-1/Acetylcysteine; 73-31-4/Melatonin; EC Oxide Synthase; EC Oxide Synthase Type II; EC Oxide Synthase Type III

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