Melatonin interactions with blood pressure and vascular function during L-NAME-induced hypertension.
The mechanisms responsible for the antihypertensive effect of melatonin are not completely understood. To elucidate the possible role of the nitric oxide (NO) pathway in the hemodynamic actions of melatonin, the effects of this indolamine on vascular function during hypertension induced by the NO-synthase (NOS) inhibitor, N(omega)-nitro-L-arginine-methyl ester (L-NAME) were investigated. Four groups of male adult Wistar rats were employed: control, L-NAME (40 mg/kg), melatonin (10 mg/kg) and L-NAME + melatonin for 5 wks. Systolic and diastolic blood pressure were measured invasively in the carotid artery. Conjugated dienes concentration (an oxidative load marker), NOS RNA expression and its activity and RNA expression of cyclooxygenase-(COX)-1 and COX-2 were determined in the aorta. Acetylcholine-induced responses and their NO-mediated component were evaluated in femoral and mesenteric artery. Moreover, endothelium-derived constricting factor (EDCF)-dependent vasoconstriction and inner diameter were determined in the femoral artery. Chronic L-NAME treatment induced hypertension, elevated the oxidative load and inhibited NOS activity. Moreover, impaired NO-dependent relaxation, augmented EDCF-constriction, increased COX-2 expression and reduced arterial inner diameter were observed. Melatonin added to L-NAME treatment completely prevented elevation of the oxidative load in the aorta. However, melatonin was not able to prevent NOS activity decline, elevation of COX-2 expression or the impairment of vascular responses (except moderate improvement in relaxation of small mesenteric arteries) and it exerted only slight antihypertensive effect. In conclusion, in addition to the reduction of the oxidative load, the restoration of the NO pathway seems to play an important role in the antihypertensive effect of melatonin.
Paulis
Ludovit
L
Center for Cardiovascular Research, Charite-Universitatsmedizin, Berlin, Germany. ludo@lfuk.sk
Pechanova
Olga
O
Zicha
Josef
J
Barta
Andrej
A
Gardlik
Roman
R
Celec
Peter
P
Kunes
Jaroslav
J
Simko
Fedor
F
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000096:biosynthesis; D016232:Endothelins / Q000494:pharmacology; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology*; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D019331:NG-Nitroarginine Methyl Ester; D019001:Nitric Oxide Synthase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014664:Vasodilation / Q000187:drug effects*
D000959:Antihypertensive Agents; D016232:Endothelins; D019001:Nitric Oxide Synthase; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; D008550:Melatonin; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester