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P. MORSING A. STENBERG D. CASELLAS A. MIMRAN C. MÜLLER-SUUR C. THORUP L. HOLM A. E. G. PERSSON 《Acta physiologica (Oxford, England)》1992,146(3):393-398
Atrial natriuretic peptide (ANP), injected at physiological concentrations, is known to induce both natriuresis and diuresis. It has been suggested by some investigators that these changes result from an increasing glomerular filtration rate (GFR), but others have been unable to demonstrate an increased GFR. The tubuloglomerular feedback (TGF) mechanism is an important regulator of GFR, and the sensitivity of TGF is decreased during ANP administration. Furthermore, resetting of TGF is, in most instances, related to changes in renal interstitial hydrostatic and oncotic pressures. It is also known that ANP may increase capillary permeability which may change renal interstitial pressure. The present study was performed to examine renal interstitial pressures and the TGF mechanism during ANP infusion. In accordance with previous studies, TGF sensitivity was found to be decreased. The tubular flow rate which elicited half the maximal drop in stop-flow pressure (Psf) was increased from 18.5 to 25.7 nl min-1. In contrast, ANP infusion resulted in a decreased interstitial hydrostatic pressure and an increased interstitial oncotic pressure. From previous experiments, such changes in interstitial pressures would be expected to increase TGF sensitivity. The changes in interstitial pressure cannot, therefore, directly explain the resetting of the feedback mechanism. In conclusion, the present paper shows a decreased renal net interstial pressure after intravenous administration of ANP. 相似文献
64.
蝎毒多肽对大鼠纤溶系统的作用 总被引:1,自引:0,他引:1
从蝎毒中获取具有多种药理活性的肽类混合物(简称SVP),用下肢血管灌流和整体给药的动物模型,观察对血管灌流液内纤溶酶原激活物(PA)活性、血浆优球蛋白纤溶活性(EFA)、纤溶酶(PL)活性的影响。结果:1~20μg/ml灌流3min和0.8,1.6mg·kg-1ipSVP1h血浆中PA活性与对照组相比明显升高(P<0.05或P<0.01),这可能与血管内皮细胞释放PA活性增加有关。 相似文献
65.
Lundin Pål D. P. Lundin Stefan Olsson Håkan Karlsson Börje W. Weström Björn R. Pierzynowski Stefan G. 《Pharmaceutical research》1995,12(10):1478-1482
Purpose. The present investigation was done to study the intestinal absorption of three oxytocin peptide analogues and to elucidate the role of pancreatic juice on their absorption.
Methods. In conscious chronically catheterized pigs (6–8 weeks of age) plasma concentration of the peptides, [Mpa1, D-Tyr(Ethyl)2, Thr4, Orn8]-oxytocin (F314), [Mpa1, D-Tyr(Ethyl)2, Val4, D-Arg8]-oxytocin (CAT), and [Mpa1, D-Tyr(Ethyl)2, Thr4, Orn8, desGly9, carba6]-oxytocin (F327) after intraduodenal administration, during presence or diversion of the pancreatic juice via a pancreatic duct catheter, were determined by radioimmunoassay. The stability of the peptides to degradation was determined in vitro by incubation with activated pancreatic juice, chymotrypsin or trypsin, followed by reversed phase HPLC analyses.
Results. All peptides were absorbed with a bioavailability of about 0.5% in the presence of pancreatic juice, but increased to 1.0%, 2.1%, and 13.5% for F314, CAT, and F327, respectively, when the pancreatic juice was diverted from the intestine. After incubation with pancreatic juice 95% of F314, 98% of F327, and 100% of CAT was found intact. When incubated with trypsin CAT remained intact while F314 and F327 were degraded by 54% and 46%, respectively. Incubation with purified chymotrypsin did not degrade the test peptides.
Conclusions. The results indicate that the increased absorption of peptides observed under conditions of diverted pancreatic juice cannot only be explained by the absence of pancreatic enzymes, but also by changed absorptive properties in the gastrointestinal tract. 相似文献
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67.
测定7例心力衰竭患儿及44例健康儿童血浆心钠素浓度,发现心力衰竭患儿血浆心钠素浓度较健康儿童增加,且与病情轻重有关,心力衰竭程度越重,心钠素浓度越高,此系心脏通过降低心脏前、后负荷以改善心功能的代偿机制。2个月至12岁健康儿童血浆心钠素水平不受性别及年龄的影响。 相似文献
68.
In an attempt to establish an in vitro/in situ correlation of intestinal permeability data, the permeability coefficients (P
app) for a series of model peptides, which were determined using an in situ perfused rat ileum model, were compared to the permeability coefficients (P
mono) determined using an in vitro cell culture model (Caco-2). The model peptides, which were all blocked on the N-terminal (acetyl, Ac) and the C-terminal (amide, NH2) ends, consisted of D-phenylalanine (F) residues (e.g., AcFNH2, AcFFNH2, AcFFFNH2). To alter the degree of hydrogen bonding potential, the nitrogens of the amide bonds were sequentially methylated [e.g., AcFF(Me)FNH2, AcF(Me)F(Me)FNH2, Ac(Me)F(Me)F(Me)FNH2, Ac-(Me)F(Me)F(Me)FNH(Me)]. These peptides were shown not to be metabolized in the in situ perfused rat ileum system. The results of the transport experiments showed that there were poor correlations between the apparent permeability coefficients (P
app) determined in an in situ perfused rat ileum model and the octanol–water partition coefficients (r = 0.60) or the hydrogen bonding numbers (r = 0.63) of these peptides. However, good correlations were observed between the in situ
P
app values for these peptides and their partition coefficients in heptane–ethylene glycol (r = 0.96) and the differences in their partition coefficients between octanol–water and isooctane–water (r = 0.86). These results suggest that lipophilicity may not be the major factor in determining the intestinal permeability of these peptides and that hydrogen bonding potential may be a major contributing factor. A good correlation (r = 0.94) was also observed between the P
app values determined for these peptides in the in situ perfused ileum model and those P
mono values determined in the in vitro cell culture model (Caco-2) (Conradi et al., Pharm. Res. 8:1453–1460, 1991). These results suggest that the permeability values determined in the Caco-2 cell culture model may be a good predictor of the intestinal permeability of peptides. 相似文献
69.
The synthesis is of Tyr(P)-containing peptides by the use of Fmoc-Tyr(PO3Me2)-OH in Fmoc/solid phase synthesis is complicated since, firstly, piperidine causes cleavage of the methyl group from the -Tyr(PO3 Me2)-residue during peptide synthesis and, secondly, harsh conditions are needed for its final cleavage. A very simple method for the synthesis of Tyr(P)-containing peptides using t-butyl phosphate protection is described. The protected phosphotyrosine derivative, Fmoc-Tyr(PO3tBu2)-OH was prepared in high yield from Fmoc-Tyr-OH by a one-step procedure which employed di-t-butyl N,N-diethyl-phosphoramidite as the phosphorylation reagent. The use of this derivative in Fmoc/solid phase peptide synthesis is demonstrated by the preparation of the Tyr(P)-containing peptides, Ala-Glu-Tyr(P)-Ser-Ala and Ser-Ser-Ser-Tyr(P)-Tyr(P). 相似文献
70.
目的研究鞘内注射吗啡对大鼠中脑导水管周围灰质(PAG)、海马和脊髓μ阿片受体(MOR)mRNA表达的影响,探讨大鼠鞘内注射吗啡免疫功能抑制的机制。方法清洁级成年雄性SD大鼠,鞘内置管成功的16只大鼠随机分为2组(n=8):生理盐水组(NS组)和吗啡组(M组)。M组鞘内持续输注吗啡10μg/h 7 d(生理盐水稀释),NS组给予等体积的生理盐水。输注7 d后断头处死大鼠,取出大鼠PAG、海马和脊髓标本,采用巢式RT-PCR测定MOR mRNA的表达。结果与NS组比较,M组PAG和海马MOR mRNA表达下调(P〈0.05或0.01),脊髓MOR mRNA表达无统计学意义(P〉0.05)。结论大鼠PAG和海马MOR表达下调可能是鞘内注射吗啡导致免疫功能抑制的机制之一。 相似文献