INTERACTION BETWEEN EPIDERMAL GROWTH FACTOR AND ARGININE VASOPRESSIN IN RENAL MEDULLARY MEMBRANES

1. Epidermal growth factor is a potent mitogen that causes natriuresis, diuresis and inhibition of arginine vasopressin-induced water reabsorption. 2. The aim of this study was to determine any interaction between epidermal growth factor and the V1 (vascular) and/or V2 (antidiuretic) arginine vasopressin receptor subtypes. 3. Radioligand binding displacement assays demonstrated that although arginine vasopressin related peptides displaced both radioligands from renal medullary membranes at low concentrations epidermal growth factor displaced neither. 4. Arginine vasopressin V2 receptor second messenger cyclic adenosine monophosphate (CAMP) production was inhibited by epidermal growth factor (IC₅₀ 2 ± 10^?7 mol/L) as was sodium fluoride cAMP production but only at much higher concentrations. 5. Therefore the diuretic effect of epidermal growth factor is not via direct antagonism of arginine vasopressin receptors but seems mediated via inhibition of the V2 second messenger system.     

中枢和外周脑钠素(BNP)调节醛固酮分泌的不同作用

将BNP和AT-Ⅱ、ACTH AVP单独或BNP与这3种肽分别合并在大鼠icv或iv注入后观察血Ald浓度的变化。实验结果表明:①iv给予AVP(5μg/3ml·h~(-1))、ACTH(5μg/3ml·h~(-1))和AT-Ⅱ(5 v.g/3 ml·h(-1)),1h后均能增加血Ald的浓度。iv给予BNP(5μg/3ml·h(-1))能明显抑制AVP和ACTH的刺激作用,而不影响AT-Ⅱ的刺激作用。②icv给予BNP(2 Vg/10 pl NS)能降低血Aid浓度。icv给予AVP(2μg/10μl NS)能增加血Aid浓度,但ACTH(2μg/10μl NS)和AT-Ⅱ(2μg/10μl NS)无此种作用。但如脑室同时给予BNP(2μg/10μlNS)却可明显刺激Aid分泌。③icv注入BNP对外周注入的3种多肽的刺激作用无任何影响。从上述的实验结果可看出:脑内BNP可“反常”地增加AT-Ⅱ、ACTH和AVP对Ald分泌的刺激作用,与外周抑制AVP,ACTH的刺激作用不同。而脑内BNP不影响这3种多肽的外周刺激作用。结论是脑内BNP以其独特的方式调节Ald的分泌,控制水盐代谢。     

左旋硝基精氨酸诱导高血压大鼠心肌肥大

一氧化氮合酶（ＮＯＳ）抑制剂Ｎ－左旋硝基精氨酸（Ｎ－ＬＮＡ）诱导持续性高血压大鼠１２只，随机分成２组测右颈动脉压，ＮＯ代谢物亚硝酸盐（ＮＯ２）浓度，心肌组织胶原蛋白含量及丝裂活化蛋白激酶（ＭＡＰＫ）活性，观察左心室心肌病理变化，发现与高血压比较，自然归组大鼠动脉血完全逆转（Ｐ〈０．０１）；ＮＯ２水平及ＭＡＰＫ活性轻度逆转，但均未达到正常对照组水平（Ｐ〈０．０１），胶原蛋白含量，心脏及左心室相对重量     

NIFEDIPINE BLOCKS ACTH AND CORTISOL RELEASE IN MAN

1. The present study investigated the effect of prior administration of nifedipine on AVP-induced ACTH release in seven normal volunteers. Three protocols were used: 20 mg oral nifedipine; 0.14 pressor units intramuscular (i.m.) per kg bodyweight aqueous AVP; oral nifedipine plus i.m. AVP 90 min later. Plasma ACTH and cortisol were measured at intervals for 2.5 h during each test. 2. The mean peak plasma ACTH and cortisol levels and the mean peak changes from basal in these levels were significantly lower in the nifedipine/AVP test than in the AVP alone test. The integrated area under the cortisol time curve was significantly lower for the nifedipine/AVP test than that for the AVP test alone. Nifedipine alone caused no changes in ACTH or cortisol. 3. Acute administration of oral nifedipine caused an inhibition of AVP-stimulated ACTH and cortisol release in normal humans. This effect may be due to blockade of plasma membrane calcium channels normally activated during AVP stimulation of pituitary corticotrophs.     

Effects of arginine, S-adenosylmethionine and polyamines on nerve regeneration

Introduction - Axon growth and axon regeneration are complex processes requiring an adequate supply of certain metabolic precursors and nutrients. Material and methods - This article reviews the studies examining some of the processes of protein modification fundamental to both nerve regeneration and to the continuous and adequate supply of specific factors such as arginine, S-adenosylmethionine and polyamines. Results - The process of arginylation notably increases following nerve injury and during subsequent regeneration of the nerve, with the most likelyfunction of arginine-modification of nerve proteins being the degradation of proteins damaged through injury. It appears that defective methyl group metabolism may be one of the leading causes of demyelination, as suggested by the observation of reduced cerebrospinal fluid concentrations of s-adenosylmethionine (SAMe) and 5-methyltetrahydrofolate, the key metabolites in methylation processes, in patients with a reduction in myelination of corticospinal tracts. Polyamine synthesis, which depends strongly on the availability of both SAMe and arginine, markedly increases in neurons soon after an injury. This "polyamine-response" has been found to be essential for the survival ofthe parent neurons after injury to their axons. Polyamines probably exert their effects through involvement in DNA, RNA and protein synthesis, or through post-translational modifications that areindicated as the most relevant events of the "axon reaction." Conclusions - Nerve regeneration requires the presence of arginine, s-adenosylmethionine, and polyamines. Further studies are needed to explore the mechanisms involved in these processes.     

ACUTE EFFECT OF ETHANOL ON RENAL ELECTROLYTE TRANSPORT IN THE RAT

1. Despite human and animal studies, the direct effect of ethanol on renal water and electrolyte transport is poorly understood. The acute effect of increasing plasma concentrations of ethanol was evaluated in a water diuretic anaesthetized rat model which inhibits endogenous arginine vaso-pressin (AVP) release. 2. Ethanol at a plasma concentration of 1.69 ±0.28 mmol/L produced an immediate increase in urine flow (174 ± 11 μL/min pre-ethanol and 189 ± 13 and then 206 ± 12 μL/min during the ethanol infusion; P<0.001) as well as an increase in fractional sodium excretion (0.17 ± 0.04 to 0.28 ± 0.05 and 0.27 ± 0.05%; P<0.001). There was also a brief phosphaturia. These increases in electrolyte excretion had returned to control values by 20 min despite a further increase in the plasma ethanol concentration. 3. The urinary excretion of potassium, calcium and magnesium was not altered nor was glomerular filtration rate or renal plasma flow. 4. Ethanol at a mean concentration of 1.60 mmol/L did not alter the action of a maximal concentration of AVP (75 ng/kg) on water or electrolyte transport. However, the antidiuretic effect of a submaximal concentration of AVP (7.5 ng/kg) was augmented by ethanol at concentrations of 1.63 and 0.98 mmol/L. 5. These studies suggest that the ethanol induced diuresis commonly ascribed to inhibition of AVP secretion may also be due to other intrarenal effects of ethanol, possibly acting within the proximal tubule. These results also confirm recent in vitro findings that while ethanol does not inhibit the action of a maximal concentration of AVP, it does modulate the effects of lower AVP concentrations.     

L-精氨酸对高原肺水肿患者血液流变学的作用

目的：探讨雾化吸入左旋精氨酸（L-Arg）对高原肺水肿患者血液流变学的影响。方法：在海拔3700m高原，采用氧气驱动雾化吸入L-Arg，治疗高原肺水肿（HAPE）患者9例（L-Arg组），将吸入低浓度一氧化氮（NO）混合气治疗的另外8例高原肺水肿患者（NO组）作对照，分别测定患者的红细胞压积（HCT）、血液粘度（ηb）、血浆粘度（ηp）、还原粘度（ηr）、红细胞刚性指数（IR）、红细胞变形系数（TK）、红细胞聚集系数（VAI）和血栓形成系数（TFL）等血液流变学指标。结果：NO组和L-Arg组治疗后较治愈前ηb、ηp、ηr、VAI、TFL均降低显著（P〈0．05～0．01），而HCT、TK、IR无统计学差异（P〉0．05）；NO组与L-Arg组比较，各指标均无统计学差异（P〉0．01）。结论：L-Arg治疗HAPE有效，通过提高NO水平而改善血液循环，且经济简便，易于推广应用。     

左旋精氨酸对兔肺缺血再灌注损伤的保护作用

目的 :观察左旋精氨酸对在体兔肺缺血再灌注损伤的影响。方法 :复制在体兔肺缺血再灌注损伤模型。 30只日本雄性大耳兔 ,随机分为三组 :假手术组 ,缺血再灌注组 (IR组 )和左旋精氨酸 +缺血再灌注组(Larg组 )。对比观察各组血浆SOD活力 ,NO、MDA含量 ,肺组织湿干重比 (W /D) ,肺损伤组织学定量评价指标 (IQA)及光镜和电镜下的组织形态学改变。结果 :缺血再灌注后Larg组血浆NO含量和SOD活力较S组、IR组明显升高 (P <0 .0 1) ,MDA、W/D、IQA较IR组明显降低 (P <0 .0 5 ,P <0 .0 5 ,P <0 .0 1) ;IR组镜下见有肺组织水肿 ,肺泡损伤严重 ,内皮细胞线粒体水肿或空泡化 ,毛细血管内炎性细胞浸润 ;而Larg组肺组织上述改变明显减轻。结论 :在体兔肺缺血前预先用L Arg处理 ,可减轻随后的缺血再灌注损伤 ;其机制之一可能与L Arg抗氧自由基作用有关     

反相高压液相色谱法测定血清中部分氨基酸

目的：建立测定血清中精氨酸含量的方法。方法：反相高压液相色谱法。ＨｙｐｅｒｓｉｌＢＤＳ柱，邻苯二甲醛柱前衍生化、萤光检测法检测。结果：精氨酸线性范围为３８３μｍｏｌ／Ｌ～４７８９μｍｏｌ／Ｌ，８种氨基酸的最低检测限为２μｍｏｌ／Ｌ，日内变异系数为２７５％～１１９３％，日间变异系数为７０５％～１２３９％，５种氨基酸的回收率为９６３３％～１００７８％。正常人血清精氨酸水平为９２７７±１７９０μｍｏｌ／Ｌ，糖尿病患者血清精氨酸水平则为７８６１±３３０３μｍｏｌ／Ｌ（Ｐ＞００５）。结论：本方法简单易行，方法学实验结果满意，适用于临床测定相关氨基酸的需要     

精氨酸对创伤大鼠免疫调节作用的研究

研究了腹部创伤大鼠免疫功能的变化及精氨酸对创伤大鼠的免疫调节作用。结果显示：腹部创伤大鼠脾脏自发性抑制性Ｔ淋巴细胞活性明显增强，脾脏淋巴细胞白细胞介素２生成能力明显下降；应用精氨酸治疗能够明显地降低自发性抑制性Ｔ淋巴细胞活性，促进脾脏淋巴细胞白细胞介素２的产生。结果表明：创伤大鼠免疫功能明显下降，应用精氨酸治疗能够明显改善创伤大鼠的免疫功能，有助提高其抗感染力．