Nowicki P T
Department of Pediatrics, Ohio State University, Columbus, Ohio 43210, USA.
Am J Physiol. 1998 Jun;274(6):G1142-50. doi: 10.1152/ajpgi.1998.274.6.G1142.
Studies were conducted in young postnatal swine to determine if substance P (SP) participates in the regulation of postnatal intestinal hemodynamics and oxygenation. SP was present in homogenates of whole intestine from postnatal swine in an age-dependent manner as follows: 1 day old and never fed, 126 +/- 35; 3 days old and fasted, 148 +/- 30; and 14 days old, 51 +/- 10 pg/mg protein (P < 0.01, 14- vs. 1- or 3-day-olds). Phenylephrine-precontracted rings of mesenteric artery from 3-day-old subjects mounted for tension recording within buffer-filled myographs demonstrated brisk relaxation in response to SP (EC50, 2 x 10(-10) M). This relaxation was eliminated by mechanical removal of the endothelium or blockade with the L-arginine analog NG-monomethyl-L-arginine (L-NMMA) and was significantly attenuated by pretreatment with N-acyl-L-Trp-3,5-bis-(trifluoromethyl) benzyl ester (NATB), a highly selective NK-1 receptor antagonist (pA2 5 x 10(-10) M). Infusion of exogenous SP into the mesenteric artery of innervated in vivo gut loops reduced intestinal vascular resistance 35% and increased tissue oxygen uptake 40% in both 3- and 14-day-old subjects. By contrast, blockade of the NK-1 receptor for SP with NATB increased intestinal vascular resistance 19% in 3-day-old subjects but only 5% in 14-day-old subjects (P < 0.01). SP-induced changes in gut vascular resistance were significantly attenuated by prior coinfusion of NATB or L-NMMA, indicating that the peptide exerted this vascular effect via theNK-1 receptor, which is linked to endothelial cell nitric oxide synthase. Both NATB and L-NMMA attenuated flow-induced dilation within pump-perfused in vitro gut loops from 3-day-old subjects. SP appears to participate in the regulation of the newborn intestinal circulation, especially during the first days after birth.
在新生仔猪中进行了多项研究，以确定P物质（SP）是否参与调节出生后肠道的血流动力学和氧合作用。出生后仔猪全肠匀浆中存在SP，其含量随年龄变化如下：出生1天且未喂食，126±35；出生3天且禁食，148±30；出生14天，51±10 pg/mg蛋白质（P<0.01，14天龄与1天龄或3天龄相比）。对来自3天龄仔猪的肠系膜动脉进行苯肾上腺素预收缩，将其置于充满缓冲液的肌动描记器中记录张力，结果显示对SP有快速舒张反应（半数有效浓度，2×10⁻¹⁰ M）。通过机械去除内皮或用L-精氨酸类似物NG-单甲基-L-精氨酸（L-NMMA）阻断可消除这种舒张反应，而用N-酰基-L-色氨酸-3,5-双-（三氟甲基）苄酯（NATB）预处理可显著减弱这种舒张反应，NATB是一种高度选择性的NK-1受体拮抗剂（拮抗常数5×10⁻¹⁰ M）。将外源性SP注入体内有神经支配的肠袢的肠系膜动脉中，在3天龄和14天龄的仔猪中，均可使肠道血管阻力降低35%，组织氧摄取增加40%。相比之下，用NATB阻断SP的NK-1受体，在3天龄仔猪中可使肠道血管阻力增加19%，而在14天龄仔猪中仅增加5%（P<0.01）。预先同时注入NATB或L-NMMA可显著减弱SP引起的肠道血管阻力变化，表明该肽通过与内皮细胞一氧化氮合酶相关的NK-1受体发挥这种血管效应。NATB和L-NMMA均可减弱3天龄仔猪体外泵灌注肠袢中血流诱导的扩张。SP似乎参与了新生肠道循环的调节，尤其是在出生后的头几天。
