Sofronova Svetlana I, Borzykh Anna A, Gaynullina Dina K, Kuzmin Ilya V, Shvetsova Anastasia A, Lukoshkova Elena V, Tarasova Olga S
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.
Institute for Biomedical Problems, Russian Academy of Sciences, Khoroshevskoe shosse 76A, 123007, Moscow, Russia.
Nitric Oxide. 2016 May 1;55-56:1-9. doi: 10.1016/j.niox.2016.02.005. Epub 2016 Feb 23.
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.
在成熟过程中，血管系统会经历结构和功能重塑。在全身水平上，这会导致出生后个体发育过程中动脉血压逐渐升高。出生后早期发育阶段将血压维持在相对较低水平的机制尚未完全明了。最近我们发现，幼龄（1 - 2周龄）大鼠的后肢动脉表现出增强的内皮型一氧化氮（NO）途径活性，与成年大鼠的动脉相比，其收缩反应性减弱。在此，我们检验了一个假设，即整个血管系统中内皮型NO的持续性生成增加，会导致幼龄大鼠的全身血压水平降低。
从小肠系膜、隐静脉、腓肠和肾内动脉分离出幼龄（2周龄）、幼年（4周龄）和成年（10 - 12周龄）雄性大鼠的血管段，在钢丝等长肌动描记器中进行测试。通过一氧化氮合酶（NOS）抑制剂L - NNA对动脉自发张力和对甲氧明（α1 -肾上腺素能受体激动剂）的收缩反应的影响来评估NO的抗收缩作用。此外，通过定量聚合酶链反应（qPCR）测定动脉标本中内皮型一氧化氮合酶（eNOS）和精氨酸酶 - 2 mRNA的表达，并通过格里斯反应测定血清亚硝酸盐/硝酸盐水平。用颈动脉内导管测量清醒大鼠的血压。
在2周龄大鼠的所有动脉中，除肾动脉外，L - NNA处理导致显著的张力性收缩以及对甲氧明收缩反应的显著增强。L - NNA的作用随年龄增长逐渐减弱，到10 - 12周时，在小肠系膜动脉中的作用变得非常小，在腓肠和隐静脉动脉中则消失。尽管未发现eNOS mRNA表达有差异，但与成年大鼠相比，幼龄大鼠精氨酸酶 - 2 mRNA的含量显著更低。2周龄大鼠血清中NO代谢产物水平比成年大鼠高两倍。与此同时，幼龄大鼠的动脉血压比成年大鼠低一半，但在给予L - NAME后，幼龄大鼠的血压升高比成年大鼠更显著。
在幼龄大鼠中，内皮持续释放NO会显著减弱供应肠道、皮肤和骨骼肌的动脉的收缩反应，这些组织接受了很大比例的心输出量。NO的这种抗收缩作用可能是未成熟循环系统中血压降低的重要机制。
