Melatonin prevents fibrosis but not hypertrophy development in the left ventricle of NG-nitro-L-arginine-methyl ester hypertensive rats.
OBJECTIVE
Melatonin was shown to reduce blood pressure, enhance nitric oxide availability and scavenge free radicals. There is, however, a shortage of data with respect to the effect of melatonin on pathological left ventricular remodelling associated with haemodynamic overload.


METHODS
We investigated whether melatonin was able to prevent left ventricular hypertrophy (LVH) and fibrosis associated with N(G)-nitro-L-arginine-methyl ester (L-NAME)-induced hypertension.


METHODS
Four groups of male Wistar rats were investigated: control, L-NAME (50 mg/kg per day), melatonin (10 mg/kg per day) and L-NAME plus melatonin. Blood pressure was measured non-invasively each week. After 5 weeks of treatment the animals were killed and nitric oxide synthase (NOS) activity, endothelial and inducible NOS expression, the level of collagenous proteins, hydroxyproline and conjugated dienes in the left ventricle were determined.


RESULTS
The administration of L-NAME inhibited NOS activity, increased conjugated dienes concentration, elevated blood pressure and induced LVH and fibrosis (indicated by increased collagenous proteins and hydroxyproline levels). The addition of melatonin to L-NAME treatment failed to prevent the attenuation of NOS activity and the development of LVH and prevented hypertension only partly. The administration of melatonin, however, completely prevented the increase in conjugated dienes concentration and the development of left ventricular fibrosis. NOS expression was not different among experimental groups.


CONCLUSIONS
Melatonin prevented the development of left ventricular fibrosis and the increase in oxidative load in rats with L-NAME-induced hypertension. The antifibrotic effect of melatonin seems to be independent of its effects on NOS activity and might be linked to its antioxidant properties.
Paulis
Ludovit
L
Center for Cardiovascular Research, Charité-Universitätsmedizin, Berlin, Germany. ludo@lfuk.sk
Pechanova
Olga
O
Zicha
Josef
J
Krajcirovicova
Kristina
K
Barta
Andrej
A
Pelouch
Vaclav
V
Adamcova
Michaela
M
Simko
Fedor
F
D000818:Animals; D001794:Blood Pressure; D005355:Fibrosis / Q000517:prevention & control*; D016166:Free Radical Scavengers / Q000494:pharmacology; D006352:Heart Ventricles / Q000187:drug effects / Q000473:pathology*; D006439:Hemodynamics; D006909:Hydroxyproline / Q000378:metabolism; D006984:Hypertrophy / Q000517:prevention & control*; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D019331:NG-Nitroarginine Methyl Ester / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar
D016166:Free Radical Scavengers; D008550:Melatonin; D006909:Hydroxyproline; D019331:NG-Nitroarginine Methyl Ester