Melatonin improves the restoration of endothelium-derived constricting factor signalling and inner diameter in the rat femoral artery after cessation of L-NAME treatment.
OBJECTIVE
Melatonin is suggested to be beneficial in several pathological conditions including arterial hypertension. One of the mechanisms proposed for its antihypertensive action is the protection against endothelial dysfunction. We investigated whether melatonin can accelerate the recovery from N(G)-nitro-L-arginine-methyl ester (L-NAME)-induced hypertension after the cessation of L-NAME administration.


METHODS
Male adult Wistar rats (n=40) were randomized into 3 treated groups: 5-week L-NAME, 5-week L-NAME + 3-week vehicle, 5-week L-NAME + 3-week melatonin and into 2 age-matched control groups. The blood pressure was measured in the carotid artery. The NO-signalling was represented by NO-synthase activity and expression in the aorta and NO-mediated relaxations of femoral and mesenteric arteries. The endothelium-derived-constricting factor (EDCF)-signalling was represented by aortic cyclooxygenase-2 expression and femoral EDCF-mediated contractions. Oxidative load was determined in the aorta based on conjugated dienes concentration and inner diameter was measured in femoral arteries.


RESULTS
L-NAME caused hypertension, reduced NO-signalling and arterial diameter and increased oxidative load and EDCF-signalling. While the NO-signalling was restored spontaneously 3 weeks after L-NAME cessation, the EDCF-signalling, oxidative load and arterial remodeling were completely restored only when melatonin treatment was administered during the recovery period. The blood pressure regression was comparable between spontaneous and melatonin recovery.


CONCLUSIONS
Although melatonin did not accelerate blood pressure reduction, it attenuated EDCF-contractions and oxidative load and enlarged arterial diameter. These effects may be beneficial for cardiovascular protection.
Paulis
Ludovit
L
Center for Cardiovascular Research, Charite-Universitätsmedizin, Hessische Strasse 3-4, Berlin, Germany. ludo@lfuk.sk
Pechanova
Olga
O
Zicha
Josef
J
Liskova
Silvia
S
Celec
Peter
P
Mullerova
Martina
M
Kollar
Jakub
J
Behuliak
Michal
M
Kunes
Jaroslav
J
Adamcova
Michaela
M
Simko
Fedor
F
D000818:Animals; D001011:Aorta / Q000201:enzymology; D001794:Blood Pressure / Q000187:drug effects; D016232:Endothelins / Q000378:metabolism*; D005263:Femoral Artery / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism; D006352:Heart Ventricles / Q000187:drug effects; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects*
D016232:Endothelins; D019001:Nitric Oxide Synthase; D011451:Prostaglandin-Endoperoxide Synthases; D008550:Melatonin; D019331:NG-Nitroarginine Methyl Ester