Original articleMelatonin improves the restoration of endothelium-derived constricting factor signalling and inner diameter in the rat femoral artery after cessation of L-NAME treatmentPaulis, Ludovita,b,c; Pechanova, Olgac,d; Zicha, Josefd; Liskova, Silviad,e; Celec, Peterb,f; Mullerova, Martinab; Kollar, Jakubb; Behuliak, Michalb; Kunes, Jaroslavd; Adamcova, Michaelag; Simko, Fedorb,hAuthor Information aCenter for Cardiovascular Research, Charite-Universitätsmedizin, Berlin, Germany bInstitute of Pathophysiology, Faculty of Medicine, Comenius University, Bratislava, Slovak Republic cInstitute of Normal and Pathological Physiology, Slovak Academy of Sciences, Bratislava, Slovak Republic dInstitute of Physiology and Center of Cardiovascular Research, Academy of Sciences of the Czech Republic, Prague, Czech Republic eInstitute of Pharmacology, Faculty of Medicine, Comenius University, Bratislava, Slovak Republic fInstitute of Molecular Biomedicine, Faculty of Medicine, Comenius University, Bratislava, Slovak Republic gDepartment of Physiology, Faculty of Medicine in Hradec Kralove, Charles University, Hradec Kralove, Czech Republic hThird Clinic of Medicine, Faculty of Medicine, Comenius University, Bratislava, Slovak Republic Correspondence to Ludovit Paulis, Center for Cardiovascular Research, Charite-Univeristätsmedizin, Hessische Str. 3-4, 10115 Berlin, Germany Tel: +49 (0)30 450525294; e-mail: firstname.lastname@example.org Sponsorship: This research was supported by a Marie Curie Intra-European Fellowship 2009-237834 COME-in-CARE within the 7th European Community Framework Programme and partly supported by VEGA 1/0187/09, 2/0178/09, APVV 0538-07, GA AS CR IAA500110902, LPP-0133-06 and 2006/24-UK-03. Conflicts of interest: None. Journal of Hypertension: September 2010 - Volume 28 - Issue - p S19-S24 doi: 10.1097/01.hjh.0000388490.28213.de Buy Metrics Abstract 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 NG-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. Conclusion 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. © 2010 Lippincott Williams & Wilkins, Inc.