title: Endothelial nitric oxide weakens arterial contractile responses and reduces blood pressure during early postnatal development in rats.
abstract: During maturation the vascular system undergoes structural and functional remodeling. At the systemic level it results in a gradual increase of arterial blood pressure during postnatal ontogenesis. The mechanisms of maintaining the blood pressure at a comparatively low level during the early postnatal development are not completely understood. Recently we showed that the hindlimb arteries of young (1-2 wk-old) rats exhibited an enhanced endothelial NO-pathway activity, which weakened their contractile responsiveness compared to the arteries of adult rats. Here we tested the hypothesis that an increased tonic endothelial NO production can take place in the whole vascular system leading to a decreased level of systemic blood pressure in young rats.
  
  
  
  Segments of small mesenteric, saphenous, sural and intrarenal arteries were isolated from the young (2 wk-old), juvenile (4 wk-old) and adult (10-12 wk-old) male rats and tested in a wire isometric myograph. Anticontractile effect of NO was evaluated by the effects of NOS inhibitor L-NNA on both arterial spontaneous tone and constrictor responses to methoxamine (α1-adrenoceptor agonist). In addition, eNOS and arginase-2 mRNA expression in arterial preparations by qPCR and serum nitrite/nitrate levels by Griess reaction were estimated. Blood pressure with an intra-carotid artery catheter was measured in conscious rats.
  
  
  
  In all arteries of 2 wk rats except the renal ones, L-NNA exposure resulted in a considerable tonic contraction and a remarkable enhancement of contractile responses to methoxamine. The effect of L-NNA gradually decreased with age and by 10-12 weeks became very small in the mesenteric arteries and disappeared in the sural and saphenous arteries. Although no difference in eNOS mRNA expression was found, the content of arginase-2 mRNA was significantly lower in young rats compared to adults. Serum levels of NO metabolites were two-fold higher in 2 wk-old rats than in adult rats. Along with that, arterial blood pressure was by half lower but rose more prominently after administration of l-NAME in young rats than in adults.
  
  
  
  In young rats, tonic release of NO by the endothelium considerably weakens contractile responses of arteries supplying intestine, skin and skeletal muscles, which receive a high proportion of the cardiac output. Such anticontractile effect of NO can be an important mechanism responsible for the blood pressure reduction in immature circulatory system.
authors.affiliation: Faculty of Biology, M.V. Lomonosov Moscow State University, Leninskie Gory 1-12, 119234, Moscow, Russia; Institute for Biomedical Problems, Russian Academy of Sciences, Khoroshevskoe shosse 76A, 123007, Moscow, Russia. Electronic address: sofronova.mailbox@gmail.com.
authors.forename: Svetlana I
authors.initials: SI
authors.lastname: Sofronova
authors.affiliation: Institute for Biomedical Problems, Russian Academy of Sciences, Khoroshevskoe shosse 76A, 123007, Moscow, Russia.
authors.forename: Anna A
authors.initials: AA
authors.lastname: Borzykh
authors.affiliation: Faculty of Biology, M.V. Lomonosov Moscow State University, Leninskie Gory 1-12, 119234, Moscow, Russia; Institute for Biomedical Problems, Russian Academy of Sciences, Khoroshevskoe shosse 76A, 123007, Moscow, Russia; Department of Physiology, Russian National Research Medical University, Ostrovitianova str. 1, 117997, Moscow, Russia.
authors.forename: Dina K
authors.initials: DK
authors.lastname: Gaynullina
authors.affiliation: Faculty of Biology, M.V. Lomonosov Moscow State University, Leninskie Gory 1-12, 119234, Moscow, Russia; Institute for Biomedical Problems, Russian Academy of Sciences, Khoroshevskoe shosse 76A, 123007, Moscow, Russia.
authors.forename: Ilya V
authors.initials: IV
authors.lastname: Kuzmin
authors.affiliation: Faculty of Biology, M.V. Lomonosov Moscow State University, Leninskie Gory 1-12, 119234, Moscow, Russia; Institute for Biomedical Problems, Russian Academy of Sciences, Khoroshevskoe shosse 76A, 123007, Moscow, Russia.
authors.forename: Anastasia A
authors.initials: AA
authors.lastname: Shvetsova
authors.affiliation: Institute for Biomedical Problems, Russian Academy of Sciences, Khoroshevskoe shosse 76A, 123007, Moscow, Russia; Institute of Experimental Cardiology, Russian Cardiology Research Center, 3rd Cherepkovskaya Street 15a, 121552, Moscow, Russia.
authors.forename: Elena V
authors.initials: EV
authors.lastname: Lukoshkova
authors.affiliation: Faculty of Biology, M.V. Lomonosov Moscow State University, Leninskie Gory 1-12, 119234, Moscow, Russia; Institute for Biomedical Problems, Russian Academy of Sciences, Khoroshevskoe shosse 76A, 123007, Moscow, Russia.
authors.forename: Olga S
authors.initials: OS
authors.lastname: Tarasova
mesh_terms: D000367:Age Factors; D000818:Animals; D001119:Arginase / Q000235:genetics / Q000378:metabolism; D062186:Arterial Pressure / Q000187:drug effects*; D001158:Arteries / Q000187:drug effects / Q000502:physiology; D004730:Endothelium, Vascular / Q000378:metabolism*; D006834:Hydrazines / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism; D009573:Nitrites / Q000097:blood; D019335:Nitroarginine / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D017208:Rats, Wistar
chemical_list: D006834:Hydrazines; D009566:Nitrates; D020030:Nitric Oxide Donors; D009573:Nitrites; D012333:RNA, Messenger; D019335:Nitroarginine; D009569:Nitric Oxide; C084012:1,1-diethyl-2-hydroxy-2-nitrosohydrazine; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C113162:Arg2 protein, rat; D001119:Arginase; D019331:NG-Nitroarginine Methyl Ester
keywords: Arterial pressure; Endothelium; Nitric oxide; Postnatal development; Resistance arteries; eNOS