The nitric oxide donor nitroprusside intraperitoneally affects peritoneal permeability in CAPD.
The nitric oxide donor nitroprusside intraperitoneally affects peritoneal permeability in CAPD.
复制标题
腹腔内一氧化氮供体硝普钠影响 CAPD 的腹膜通透性。
DOI：
10.1038/ki.1997.257
复制
发表时间：
1997
影响因子：
19.6
通讯作者：
R. Krediet
中科院分区：
文献类型：
--
作者：
C. Douma;D. D. de Waart;D. Struijk;R. Krediet
硝普苷是一氧化氮（NO）供体。为了研究硝普苷对腹膜通透性和灌注的影响，进行了标准的腹膜通透性分析。10例稳定型CAPD患者在一周内两次使用葡萄糖为基础的透析液（1.36% Dianeal），加硝普苷4.5 mg/l和不加硝普苷。计算CO2的传质面积系数（MTAC）来估计腹膜血流量。测定血浆和透析液中NO的稳定代谢物硝酸盐和NO合成的第二信使cGMP。硝普苷（NP）对低分子量溶质的mtac高于对照(C)：肌酐中位数14.1 （NP）比9.9 ml/min (C)，尿素中位数21.7 （NP）比18.5 ml/min (C)，尿酸中位数10.5 （NP）比8.6 ml/min (C)（均P < 0.05）。这表明硝普塞增加了有效腹膜表面积。此外，低分子量溶质的限制系数从1.28 (C)降低到1.23 (NP) (P = 0.02)，表明对这些溶质的尺寸选择性也有一定的影响。硝普塞对血清蛋白清除率的影响更为明显。硝普苷增加β 2微球蛋白34%，白蛋白70%，IgG 77%， α 2巨球蛋白143%。对大分子的限制系数从2.29 (C)降至1.86 (NP), P < 0.01。这表明腹膜的固有渗透性增加。利用计算机模拟的动力学模型，根据孔隙理论，使用对流模型和扩散模型来分析这些影响。硝普塞导致大孔半径和小孔半径以及扩散距离的无限制面积增加。这些影响在扩散模型中更为明显。MTAC CO2没有差异：NP 76.9和C 84.1 ml/min。在两次停留期间，硝酸盐的mtac均不大于根据分子量计算的预期值。加入硝普苷后cGMP的透析液/血浆（D/P）比为0.36，范围为0.21 ~ 0.77 (C), 0.74，范围为0.23 ~ 2.50 (NP), P = 0.02。硝普苷组cGMP的D/P比根据其分子量计算的值大（P < 0.001）。这表明加入硝普苷后cGMP的局部生成是由NO诱导的。硝普苷对透析液中前列腺素（PG） PGE2、6-酮- pgf1 α和血栓素B2的浓度无显著影响。4 h内经毛细血管超滤率和净超滤率与硝普苷无显著差异。综上所述，硝普苷可增加大鼠腹膜有效表面积和固有通透性，但对腹膜血流量无影响。cGMP的D/P比大于预期表明硝普苷在NO诱导下局部生成cGMP。
Nitroprusside is a nitric oxide (NO) donor. To investigate effects of nitroprusside i.p. on peritoneal permeability and perfusion, standard peritoneal permeability analyses were performed. Ten stable CAPD patients were studied twice within one week with glucose based dialysate (1.36% Dianeal) with and without addition of nitroprusside 4.5 mg/liter. Mass transfer area coefficients (MTAC) of CO2 were calculated to estimate peritoneal blood flow. Nitrate, a stable metabolite of NO, and cGMP, a second messenger of NO synthesis, were measured in plasma and dialysate. The MTACs of low molecular weight solutes were greater with nitroprusside (NP) compared to the control dwell (C): creatinine median 14.1 (NP) versus 9.9 ml/min (C), urea 21.7 (NP) versus 18.5 ml/min (C) and urate 10.5 (NP) versus 8.6 ml/min (C) (P < 0.05 for all). This points to an increased effective peritoneal surface area with nitroprusside. Furthermore, the restriction coefficient for the low molecular weight solutes decreased from 1.28 (C) to 1.23 (NP) (P = 0.02), suggesting some effect also on the size selectivity to these solutes. The effect of nitroprusside on the clearances of serum proteins was more pronounced. The increase with nitroprusside was 34% for beta 2-microglobulin, 70% for albumin, 77% for IgG and 143% for alpha 2-macroglobulin. This reduction in size selectivity was reflected in a decrease in the restriction coefficient for macromolecules from 2.29 (C) to 1.86 (NP), P < 0.01. This implies an increase in the intrinsic permeability of the peritoneal membrane. Kinetic modeling, using computer simulations, was done to analyze these effects in terms of the pore theory, using a convection model and a diffusion model for the transport of macromolecules. Nitroprusside led to an increase of both the large pore radius and the small pore radius and of the unrestricted area over diffusion distance. These effects were more pronounced with the diffusion model. The MTAC CO2 was not different: NP 76.9 and C 84.1 ml/min. MTACs of nitrate were not greater than expected on the basis of the molecular weight during both dwells. The dialysate/plasma (D/P) ratio of cGMP was greater after addition of nitroprusside: 0.36, range 0.21 to 0.77 (C) and 0.74, 0.23 to 2.50 (NP), P = 0.02. With nitroprusside the D/P ratio of cGMP was greater than expected on the basis of its molecular weight (P < 0.001). This points to local generation of cGMP after the addition of nitroprusside, induced by NO. No differences were found in the dialysate concentrations of the prostaglandins (PG) PGE2 and 6-keto-PGF1 alpha and thromboxane B2 after addition of nitroprusside. The transcapillary ultrafiltration rate and the net ultrafiltration rate during four hours were not different with nitroprusside. In conclusion, nitroprusside i.p. increased the effective peritoneal surface area and the intrinsic permeability, but the peritoneal blood flow did not change. The greater than expected D/P ratios of cGMP point to local generation of cGMP with nitroprusside, induced by NO.