Effect of melatonin, captopril, spironolactone and simvastatin on blood pressure and left ventricular remodelling in spontaneously hypertensive rats.
OBJECTIVE
Melatonin was shown to reduce blood pressure, oxidative load and to increase nitric oxide bioavailability predisposing melatonin to have antiremodelling potential.


METHODS
The aim of this study was to show whether melatonin can reverse left ventricular remodelling in spontaneously hypertensive rats (SHR) and to compare this potential protective effect with captopril, spironolactone, or simvastatin.


METHODS
Six groups of 3-month old rats (eight per group) were treated for 5 weeks: control untreated Wistar rats, control SHR, SHR plus melatonin (10 mg/kg per 24 h), SHR plus captopril (100 mg/kg per 24 h), SHR plus spironolactone (200 mg/kg per 24 h) and SHR plus simvastatin (10 mg/kg per 24 h). Their systolic blood pressure (SBP) was measured by the tail-cuff method. The relative weights of the left ventricle, nitric oxide synthase (NOS) activity, endothelial NOS and nuclear factor kappa B (NF-kappaB) protein expression, conjugated dienes concentration, level of collagenous proteins and hydroxyproline were measured.


RESULTS
SBP was reduced by all drugs investigated but most prominently by captopril in SHR. The activity of NOS and endothelial NOS expression increased in the left ventricles of SHR compared with controls. Melatonin and spironolactone further increased NOS expression. Left ventricular oxidative load, estimated by NF-kappaB expression and conjugated dienes concentration, increased in SHR. Only melatonin reduced NF-kappaB expression and decreased conjugated diens concentration. Only captopril reduced left ventricular hypertrophy in SHR, whereas melatonin reduced collagenous protein concentration and hydroxyproline content in the left ventricle.


CONCLUSIONS
It is concluded that although melatonin, in comparison with captopril, did not reverse left ventricle hypertrophy, it reversed left ventricular fibrosis. This protection by melatonin may be caused by its prominent antioxidative effect.
Simko
Fedor
F
Department of Pathophysiology, School Medicine, Comenius University, Bratislava, Slovak Republic. fedor.simko@fmed.uniba.sk
Pechanova
Olga
O
Pelouch
Vaclav
V
Krajcirovicova
Kristina
K
Mullerova
Martina
M
Bednarova
Kristina
K
Adamcova
Michaela
M
Paulis
Ludovit
L
D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use; D000975:Antioxidants / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects*; D002216:Captopril / Q000627:therapeutic use*; D017379:Hypertrophy, Left Ventricular / Q000188:drug therapy; D007668:Kidney / Q000187:drug effects*; D008297:Male; D008550:Melatonin / Q000378:metabolism / Q000627:therapeutic use*; D000451:Mineralocorticoid Receptor Antagonists / Q000627:therapeutic use; D016328:NF-kappa B / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D019821:Simvastatin / Q000627:therapeutic use*; D013148:Spironolactone / Q000627:therapeutic use*; D020257:Ventricular Remodeling
D000959:Antihypertensive Agents; D000975:Antioxidants; D000451:Mineralocorticoid Receptor Antagonists; D016328:NF-kappa B; D013148:Spironolactone; D002216:Captopril; D019821:Simvastatin; D008550:Melatonin