内皮素在低氧性肺动脉高压大鼠肺内表达和水平变化的研究

为了确定在慢性缺氧过程中大鼠肺内内皮素（ＥＴ）－１ｍＲＮＡ是否表达及变化，采取体外转录并用地高辛－ＵＴＰ标记ＥＴ－１和ｃ－ｆｏｓＲＮＡ探针进行组织原位杂交，用放射免疫法测定血浆和肺组织匀浆ＥＴ－１浓度。结果显示，缺氧３周大鼠肺内ＥＴ－１ｍＲＮＡ表达增加，主要阳性反应部位位于血管内皮和支气管上皮细胞。ｃ－ｆｏｓｍＲＮＡ主要位于血管平滑肌和支气管平滑肌细胞。缺氧３周大鼠静脉血浆ＥＴ－１浓度为３．８５±１．５２ｎｇ／Ｌ（与对照组比较，Ｐ＜０．０５），动脉血浆为４．７２±１．６６ｎｇ／Ｌ（Ｐ＜０．０５），肺组织匀浆中为２．０５±０．６８ｎｇ／ｇ（Ｐ＜０．０５）。认为慢性缺氧可引起大鼠肺动脉压力升高，同时伴有肺血管的重建以及右心室的肥厚；随着肺动脉压的改变，其血浆和肺组织匀浆中内皮素水平显著升高。肺内ＥＴ－１的表达和产生主要位于肺血管内皮细胞以及支气管上皮细胞     

消炎痛雾化吸入对慢性支气管炎的疗效观察

采用随机、单盲、安慰剂及正常对照的方法，观察了４８例慢性支气管炎（慢支）急性发作期患者痰及血中６－酮－前列腺素Ｆ１ａ（６－ｋｅｔｏ－ＰＧＦ１ａ）、血栓素Ｂ２（ＴＸＢ２）含量的变化以及它们与疾量，痰干／湿比，肺活量实测值占预计值百分比（ＶＣ％），１秒用力肺活量占用力肺活量百分比（ＦＥＶ１％）的相关性。并观察了消炎痛对它们的影响。结果表明：慢支患者痰及血中６－ｋｅｔｏ－ＰＧＦ１ｕ及ＴＸＢ２均高于正常对照组（Ｐ＜０．０１）。痰及血中６—ｋｅｔｏ－ＰＧＦ１ａ和ＴＸＢ２与痰量和疾干／湿比里正相关（Ｐ＜０．０１）；与ＶＣ％和ＦＥＶ１％呈负相关（Ｐ＜０．０５，Ｐ＜０．０１）。与安慰剂组相比消炎痛雾化吸入可明显降低慢支患者的痰量，痰粘度和血沉（Ｐ＜０．０１）；明显提高ＶＣ％和ＦＥＶ１％（Ｐ值分别小于０．０５，Ｐ＜０．０１）；明显缩短病程（Ｐ＜０．０５）。     

银杏叶抗氧化和抗脂质过氧化损伤效应的探讨

目的探讨银杏叶抗氧化和抗脂质过氧化损伤的效应。方法检测７８例心绞痛患者经银杏叶制剂天保宁治疗前后的血浆维生素Ｃ（Ｐ－ＶＣ）、维生素Ｅ（Ｐ－ＶＥ）、β－胡萝卜素（Ｐ－β－ＣＡＲ）、过氧化脂质（Ｐ－ＬＰＯ）和红细胞超氧化物歧化酶（Ｅ－ＳＯＤ）、过氧化氢酶（Ｅ－ＣＡＴ）、谷胱甘肽过氧化物酶（Ｅ－ＧＳＨ－ＰＸ）、过氧化脂质（Ｅ－ＬＰＯ）值，在Ｃｏｍｐａｑ５８６微机上用ＳＰＳＳ／ＰＣ＋统计软件包分析处理。结果与治疗前比较，治疗后的Ｐ－ＶＣ、Ｐ－ＶＥ、Ｐ－β－ＣＡＲ、Ｅ－ＳＯＤ、Ｅ－ＣＡＴ、Ｅ－ＧＳＨ－ＰＸ平均值皆显著升高（Ｐ＜０．０１），Ｐ－ＬＰＯ、Ｅ－ＬＰＯ平均值皆显著降低（Ｐ＜０．０１）；且均与对照组无显著差异（Ｐ＞０．０５）。结论心绞痛患者体内病理性氧化反应和脂质过氧化反应在治疗后明显减缓，银杏叶制剂具有较强的抗氧化损伤和抗脂质过氧化损伤的作用     

实验缺氧性肺动脉高压大鼠的内皮素合成和分布

目的研究慢性缺氧性肺动脉高压大鼠内皮素（ＥＴ）的合成和分布。方法应用慢性减压缺氧方法（氧浓度为１０％～１０．５％，缺氧４～１８日）建立肺动脉高压动物模型，然后用放射免疫方法测定对照组和不同缺氧时间组大鼠血浆ＥＴ含量，并用免疫组织化学染色方法观察不同组大鼠肺组织ＥＴ合成和分布。结果缺氧各组大鼠血浆ＥＴ含量较对照组明显增高（Ｐ＜０．０１），但不同缺氧时间组之间ＥＴ含量差异无显著性（（Ｐ＞０．０５）；正常大鼠肺组织有极少量ＥＴ样免疫物质，主要存在于血管内皮细胞，缺氧组大鼠肺血管有大量ＥＴ样免疫物质，且不仅存在于内皮细胞，血管平滑肌细胞亦有染色。结论缺氧可能是促进肺血管内皮细胞及平滑肌细胞合成ＥＴ增加的主要原因。     

一氧化氮对缺氧性肺动脉高压大鼠血浆降钙素基因相关肽？…

目的 探讨一氧化氮（ＮＯ）对缺氧性肺动态高压（ＨＰＨ）大鼠血浆降钙素基因相关肽（ＣＧＲＰ）含量的影响。方法 将Ｗｉｓｔａｒ大鼠４０只分为四组：对照组（ｎ＝１０）,缺氧组（ｎ＝１０）,缺氧＋Ｌ－ＮＡＭＥ组（ｎ＝１０）,缺年头＋Ｌ－Ａｒｇ组（ｎ＝１０）。通过Ｐ５０压力传感器测量定四组大鼠肺动脉平均压（ＰＡＭＰ）,缺氧＋Ｌ－Ａｒｇ组的ＰＡＭＰ显著低于缺氧组（Ｐ〈０．０５）;缺氧组的右室（ＲＶ）干重／左室     

血管利钠肽减弱去甲肾上腺素对心肌生长的刺激作用

本实验目的在于研究血管利钠肽（ Ｖ Ｎ Ｐ）对去甲肾上腺素（ Ｎ Ｅ）促心肌生长作用的影响,并对其机制进行探讨。分离、培养乳鼠心肌细胞,完全随机分为三组:对照组、 Ｎ Ｅ组和 Ｖ Ｎ Ｐ＋ Ｎ Ｅ组。以 Ｍ Ｔ Ｔ法和总蛋白含量测定法观察各组细胞的生长情况。进而采用放射免疫方法研究了 Ｖ Ｎ Ｐ对细胞内ｃ Ｇ Ｍ Ｐ,ｃ Ａ Ｍ Ｐ水平的影响。结果发现: Ｎ Ｅ（１０－ ７ ｍ ｏｌ／ Ｌ～１０－ ５ ｍ ｏｌ／ Ｌ）可以使培养的乳鼠心肌细胞 Ｍ Ｔ Ｔ Ｏ Ｄ值显著升高（ Ｐ＜ ０．０５ ｖｓ 对照组）,并且具有剂量依赖性。 Ｖ Ｎ Ｐ（１０－ ７ ｍ ｏｌ／ Ｌ）可以显著降低 Ｎ Ｅ（１０－ ６ ｍ ｏｌ／ Ｌ） 刺激的心肌细胞 Ｍ Ｔ Ｔ Ｏ Ｄ值和细胞内总蛋白含量（ Ｐ＜０．０５ ｖｓ Ｎ Ｅ组）。对照组和 Ｎ Ｅ组细胞内ｃ Ｇ Ｍ Ｐ,ｃ Ａ Ｍ Ｐ水平无显著差异,而 Ｖ Ｎ Ｐ（１０－ ７ ｍ ｏｌ／ Ｌ）能升高细胞内ｃ Ｇ Ｍ Ｐ水平,降低ｃ Ａ Ｍ Ｐ水平（ Ｐ＜ ０．０５ ｖｓ对照组、 Ｎ Ｅ组）。提示 Ｖ Ｎ Ｐ能减弱 Ｎ Ｅ对心肌生长的刺激作用,其机制可能与ｃ Ｇ Ｍ Ｐ,ｃ Ａ Ｍ Ｐ等信号转导分子有关。     

肝动脉栓塞致胃粘膜损伤的实验研究

目的研究肝动脉栓塞致胃粘膜损伤的机制．方法日本大耳白兔３２只，随机分为３组：正常组８只，假手术对照组８只，肝动脉栓塞组１６只．用超液态碘油制兔部分肝动脉栓塞模型．在手术前后，用放免法测定其血浆中内皮素（ＥＴ）水平，直接穿刺门静脉测压，激光多谱勒血流仪测定其胃粘膜血流量（以电压Ｖ表示），并观察胃粘膜组织形态学改变．结果肝动脉栓塞术后３ｄ和６ｄ兔血浆ＥＴ（ｎｇ／Ｌ，２１５±３５，２１５±４７）显著高于假手术对照组（１５５±２８，１４６±２８，Ｐ＜００１）．肝动脉栓塞术后６ｄ，其门静脉压力（ｋＰａ，１０９±０１０）明显高于对照组（０８５±００７，Ｐ＜００５）．胃粘膜血流量（３６４Ｖ±０７７Ｖ）显著低于正常组（４８１Ｖ±０４２Ｖ，Ｐ＜００５）和假手术对照组（４６５Ｖ±０３２Ｖ，Ｐ＜００５）．胃粘膜损害发生率（６８８％）显著高于对照组（２５０％，Ｐ＜００５）．结论肝动脉栓塞可使其血浆ＥＴ水平明显升高，门静脉压力增加，胃粘膜血流量下降，从而导致胃粘膜损伤     

经皮二尖瓣球囊扩张术前后血浆内皮素－1水平的对比研究

采用放射免疫分析法（ＲＩＡ）测定了３８例二尖瓣狭窄（ＭＳ）患者经皮球囊二尖瓣扩张术（ＰＢＭＶ）前后血浆内皮素－１（ＥＴ－１）水平，并与二尖瓣面积（ＭＶＡ）、左房内径（ＬＡＤ）及血液动力学参数作相关分析。结果显示：术前血浆ＥＴ－１水平较对照组显著升高（Ｐ＜０．００１），术后显著降低（与术前比Ｐ＜０．００１），但仍高于对照组（Ｐ＜０．００２）。血浆ＥＴ－１水平与平均肺动脉压、平均左房压和ＬＡＤ呈显著正相关（ｒ＝０．７８３，０．５１２和０．３５２，Ｐ＜０．００１，０．００２和０．０５），与其它血液动力学参数无明显相关关系。研究表明，ＥＴ－１在ＭＳ引起的病理生理改变中起重要作用，测定其变化，有可能作为判定病清程度及ＰＢＭＶ疗效的一个指标。     

大鼠孤束核内牛磺酸对新福林升压反应的影响及机制探讨

目的：采用核团微量注射和荧光分光光度测定的方法，探讨了孤束核牛磺酸对大鼠血压的影响及其可能的机制。　结果：（１）侧脑室注射牛磺酸可致血压降低，并呈现量效依赖关系（ Ｐ＜ ０．０１）；（２）孤束核微量注射牛磺酸，可使静脉注射新福林所致升压反应显著减弱（ Ｐ＜ ０．０１）；（３）孤束核注射牛磺酸后，静脉注射新福林，测得孤束核内去甲肾上腺素含量明显增加（ Ｐ＜ ０．０１）。　结论：大鼠孤束核内牛磺酸可能参与压力感受性反射的调节过程，易化该反射的交感抑制成分，其作用机制可能与去甲肾上腺素的合成或释放有关。     

肝硬化大鼠内脏血管组织内皮素及其基因表达的研究

目的探讨肝硬化大鼠内脏血管组织中,内皮素（ＥＴ）及其基因表达量的变化在门静脉高压形成机制中的意义。方法用放射免疫法分别测定大鼠血浆以及门静脉（ＰＶ）和肠系膜上动脉（ＳＭＡ）组织中ＥＴ含量,采用ＲＴ－ＰＣＲ技术分析ＰＶ和ＳＭＡ组织中ＥＴｍＲＮＡ表达量的变化。结果ＰＶ和ＳＭＡ组织中ＥＴ及其ｍＲＮＡ表达量,肝硬化组均显著高于正常对照组（均为Ｐ＜０．００１）;而肝硬化大鼠血管组织ＥＴ含量及ＥＴｍＲＮＡ表达量,则为ＰＶ明显高于ＳＭＡ（＜０．０５）,但正常对照组动静脉之间差异无显著性（Ｐ＞００５）。另外,内脏动静脉血管ＥＴ含量之差与门静脉压力呈显著的正相关。结论ＥＴ可能通过更多的收缩内脏静脉特别是门静脉,增加门静脉血流阻力而参与门静脉高压的形成。     

Estrogens modulate the circadian rhythm of hypothalamic beta-endorphin contents in female rats

The aim of the present study was to evaluate the changes in the diurnal rhythm of the hypothalamic beta-endorphin (beta-EP) contents in female rats as a function of circulating estrogens. With this purpose we evaluated the diurnal hypothalamic beta-EP changes (1) during the estrous cycle, and (2) in ovariectomized rats with and without acute and chronic estrogen replacement. Ovariectomized rats were treated either acutely with 10 micrograms of estradiol benzoate (EB) or chronically with 2 micrograms/day of EB for 15 days. beta-EP concentrations were measured in acid extracts of medial basal hypothalamus by a specific radioimmunoassay. During the estrous cycle, hypothalamic beta-EP concentrations showed a significant nocturnal increase, with no difference between the 4 days of the cycle. On the day of estrus, beta-EP concentrations between 12.00 and 18.00 h resulted significantly lower than in the other days of the cycle. After ovariectomy, the night-related changes in hypothalamic beta-EP disappeared. The acute administration of EB induced a significant increase in hypothalamic beta-EP after 21 h (18.00 h). On the other hand, the chronic replacement restored the nocturnal peak of hypothalamic beta-EP (18.00, 21.00, 24.00 h). The present data emphasize the role of central beta-EP in regulating the reproductive functions. Moreover, the effect of estrogen in modulating the circadian changes in hypothalamic beta-EP supports the important role of estrogens in brain function.     

Estradiol regulation of proopiomelanocortin gene expression and peptide content in the hypothalamus.

Previous studies have shown that the hypothalamic concentrations of beta-endorphin (beta-EP) and other proopiomelanocortin (POMC)-derived peptides change in the female rat following castration and gonadal steroid replacement. In this study we have measured POMC mRNA by solution hybridization assay in the medial basal hypothalamus (MBH) of ovariectomized rats treated with a regimen of estradiol (E2) that we have previously shown alters brain beta-EP peptide content. In addition the effect of progesterone (P) was also studied. In the first experiment the concentration of beta-EP and alpha-melanocyte-stimulating hormone (alpha-MSH) in the MBH of castrated rats decreased significantly after 3 weeks of E2 treatment compared to castrated unreplaced rats: beta-EP decreased from 6.00 +/- 0.46 to 4.32 +/- 0.38 ng/mg protein and alpha-MSH decreased from 3.00 +/- 0.23 to 2.35 +/- 0.15 ng/mg protein (p less than 0.05). A similar decrease in peptide content was noted in the anterior hypothalamus/preoptic area. A parallel reduction in the concentration of POMC mRNA was measured in the MBH of the E2-replaced animals: 1.17 +/- 0.14 vs. 0.72 +/- 0.08 pg/microgram RNA (p less than 0.02). In a second study castrated rats were studied after 2 weeks of E2 or E2 plus P treatment. After 2 weeks, POMC peptide levels did not change significantly in the MBH of either the E2- or E2 plus P-treated rats. POMC mRNA, however, was significantly reduced from 1.10 +/- 0.10 pg/micrograms RNA in the unreplaced rats to 0.58 +/- 0.05 and 0.61 +/- 0.06 pg/microgram RNA after E2 or E2 plus P, respectively (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of steroid hormones and antihormones on hypothalamic beta-endorphin concentrations in intact and castrated female rats

The aim of the present study was to evaluate the effects of estrogens and androgens on hypothalamic beta-endorphin (beta-EP) concentrations. Intact or castrated female rats were chronically (2 weeks) treated with estrogen (estradiol benzoate) and/or antiestrogens (clomiphene, cyclophenil or epimestrol), and with androgens (dihydrotestosterone or dehydroepiandrosterone sulphate) and/or antiandrogen (cyproterone acetate). A group of rats treated with vehicle were studied as comparison. The beta-EP concentrations were measured by radioimmunoassay on acidic extracts of rat hypothalami. The administration of clomiphene and cyclophenil significantly reduced hypothalamic beta-EP concentrations in intact rats, while both drugs or estradiol benzoate increased the peptide concentration in castrated rats. Both intact and castrated rats treated with epimestrol showed hypothalamic beta-EP concentrations higher than vehicle treated rats. The estradiol-induced increase of beta-EP was not changed by the concomitant administration of antiestrogens. The administration of dihydrotestosterone significantly decreased beta-EP concentrations in both intact and castrated female rats, while the treatment with dehydroepiandrosterone sulphate only slightly decreased beta-EP levels in intact female rats. The cyproterone acetate-chronically treated rats showed higher beta-EP concentrations than vehicle-treated rats and these changes were reversed by the concomitant addition of dihydrotestosterone or dehydroepiandrosterone sulphate. These results showed that estrogens play a positive role while androgens negatively influence the hypothalamic beta-EP concentrations in female rats, supporting the view that central beta-EP might be a target of gonadal steroid feedback signals.     

Brain beta-endorphin during pregnancy, parturition, and the postpartum period

Brain beta-endorphin (beta-EP) was measured in the rat during pregnancy, parturition, and the postpartum period. beta-EP increased in the hypothalamus, midbrain, and amygdala during gestation and remained elevated through delivery until 1-2 days postpartum. The concentration of beta-EP increased in the hypothalamus from 31.8 +/- 1.4 (+/- SE) ng/mg protein in nonpregnant controls to 41.4 +/- 1.8 and 39.2 +/- 1.9 during early (8-10 days) and late (18-20 days) pregnancy, respectively, and in the midbrain from 3.20 +/- 0.17 to 5.21 +/- 0.30 and 5.25 +/- 0.64 ng/mg protein (P less than 0.01). In another experiment, the brain content of beta-EP expressed as nanograms per region, increased from 12.6 +/- 0.29 to 14.7 +/- 0.33 in the hypothalamus, from 4.09 +/- 0.44 to 6.03 +/- 0.34 in the midbrain, and from 0.93 +/- 0.11 to 1.32 +/- 0.06 ng in the amygdala at 16-17 days of gestation compared with that in nonpregnant controls (P less than 0.01). When hypothalamic beta-EP was measured 1 week postpartum in lactating and nonlactating rats, a significant decline in the beta-EP concentration of both groups was noted compared with that measured during pregnancy; beta-EP levels were similar in the lactating and nonlactating rats. We conclude that pregnancy and parturition are associated with significant changes in brain beta-EP and suggest that beta-EP of central rather than peripheral origin may mediate changes in pain perception and maternal behavior during pregnancy.     

Secretion of beta-endorphin into the maternal circulation by uteroplacental tissues in response to hypoglycaemic stress

The placenta has been shown to contain ACTH and beta-endorphin but the roles of these peptides are unknown. To investigate whether they are released into the maternal circulation from the placenta in response to physiological stimuli the effects of hypoglycaemic stress were investigated. Plasma samples were collected from the femoral artery (FA) and uterovarian (UV) vein of nine pregnant sheep before and during hypoglycaemia induced by intravenous insulin (100U). Plasma concentrations of ovine beta-endorphin (o beta-EP) were measured by radioimmunoassay. Concentrations of o beta-EP rose in both vessels by 60 min after insulin. The peak concentrations of o beta-EP (pmol/l) were 122 +/- 29 (mean +/- SEM, n = 8) in the UV and 96 +/- 24 (n = 9) fmol/ml in the FA 60 min after insulin injection. There was no difference between the concentrations of o beta-EP in the vessels before insulin injection but at 60 and 120 min after insulin the concentrations of o beta-EP were significantly higher in the UV than FA (P less than 0.02, analysis of variance). This indicates that the pregnant uterus or placenta can respond to hypoglycaemia by secreting beta-EP into the maternal circulation. It is therefore possible that placental pro-opiomelanocortin (POMC) peptides may have a role in maternal endocrinology and metabolism.     

gamma-Aminobutyric acid inhibits beta-endorphin secretion from the anterior pituitary but not the neurointermediate lobe in the rat

We have evaluated the role of gamma-aminobutyric acid (GABA) in the neuroendocrine control of beta-endorphin (beta-EP) secretion in the rat. Plasma beta-EP and beta-lipotropin (beta-LPH) levels and beta-EP-like immunoreactivity (beta-EPLI) in the anterior pituitary (AP) and neurointermediate lobe (NIL) were determined after administration of GABA antagonist or agonist drugs in male rats under resting conditions or after potent physical stresses. Bicuculline (0.1-0.8 mg/kg BW ip), a GABA receptor antagonist, induced a dose-related rise in plasma beta-EP and beta-LPH levels and a concomitant decrease in beta-EPLI concentrations in the AP but not in the NIL. Muscimol, a potent GABA-mimetic drug, did not alter baseline plasma beta-EP and beta-LPH levels, whether given systemically (1.0-2.0 mg/kg BW ip) or intracerebroventricularly (500 ng/kg BW), but prevented the effect of bicuculline on plasma and AP-beta-EP and beta-LPH concentrations. Administration of foot shock or restraint stress induced a clear-cut activation of the AP-related beta-EP secretion, an effect that was prevented by pretreatment with muscimol. Together, these data show that GABA-ergic mechanisms, probably operating at a central nervous system level, exert an inhibitory action on resting and stimulated beta-EP and beta-LPH secretion. Since no alterations in beta-EP concentrations in the NIL occurred after manipulations with GABA-ergic drugs or stress, and these were detected only in the AP, an interaction between GABA-ergic neurons and CRF neurons is the most likely explanation for the reported findings.     

Chemical respiratory control in chronically hyperoxic cats

Chemical control of respiration in cats after chronic normobaric hyperoxia (NH; inhalation of 100% O2 for 60-67 h) was compared with that of control rats, anesthetized with pentobarbital. After chronic hyperoxia, induction of moderate hypoxia (PaO2 = 50-60 Torr) increased inspiratory time (TI) often without increasing tidal volume (VT). More intense hypoxia (PaO2 = 40-50 Torr) depressed tidal volume and further increased TI, diminishing the respiratory drive (VT/TI). Hypercapnia, on the other hand, increased tidal volume and shortened respiratory cycle time; but these responses were subnormal. The normal stimulatory effects of intravenous nicotine and inhibitory effect of dopamine on carotid chemo-receptor activity and ventilation were preserved in the NH cats. Cyanide, however, did not stimulate carotid chemoreceptor activity and ventilation. Thus, the changes in the carotid and aortic chemosensory activities elicited appropriate reflex ventilation responses, indicating that the central component of the chemoreflex was not impaired. The ventilatory depression during hypoxia despite an active chemosensory input is consistent with the lack of carotid chemosensory response to and a central depressant effect of hypoxia in the NH cats, and was presumably associated in part with an increased responsiveness of airway reflexes. We conclude that chronic hyperoxia selectively attenuated carotid chemosensory and chemoreflex responses to hypoxia.     

PLASMA IMMUNOREACTIVE β-ENDORPHIN IS ELEVATED IN URAEMIA

Plasma immunoreactive-(IR) beta-endorphin (beta-EP) and beta-lipotrophin (beta-LPH) levels were measured in 15 adult uraemic patients on chronic haemodialysis. The presence of immunoreactivity eluting in the position of beta-EP was demonstrated following submission of pooled extracts of uraemic plasma to gel permeation chromatography on Sephadex G-50. To separate beta-EP from beta-LPH, pre-dialysis plasma extracts from six individual patients, and three pools of three patients each, were submitted to sequential immune-affinity chromatography and levels were measured by radioimmunoassay. In all cases, plasma IR beta-EP concentrations were markedly increased compared with normal subjects (m +/- SEM fmol/ml; 64.4 +/- 13.7 vs. 2.3 +/- 0.2). IR beta-LPH concentrations were also increased (m +/- SEM fmol/ml; 55.7 +/- 13.2 vs. normal 6.1 +/- 0.8). In addition, post-dialysis concentrations of plasma IR beta-EP and beta-LPH were lower than pre-dialysis levels (n = 4).     

Ventilatory effects of almitrine bismesylate in congenital central hypoventilation syndrome

Patients with congenital central hypoventilation syndrome (CCHS) lack hypercapnic and hypoxic stimulation of ventilation but have demonstrated carotid body function in response to hyperoxia and to pharmacological stimulation with doxapram. This study investigated the ventilatory effects of almitrine bismesylate, a carotid body stimulant, in 12 patients with CCHS. Measurements of minute ventilation, tidal volume (VT), respiratory rate (RR) and transcutaneous PO2 (TCPO2) were taken before and after administration of 4.5 mg/kg and 6 mg/kg of almitrine. Twenty-four hour pharmacokinetic studies were performed in 7 patients who received 4.5 mg/kg and in 6 patients who received 6 mg/kg almitrine. There was no significant improvement in ventilatory and gas exchange parameters at either dose of almitrine despite appropriate peak serum concentration of the drug at the time of the studies. These results suggest that almitrine is not a useful ventilatory stimulant in children with CCHS.     

Involvement of vasopressin in the cardiovascular effects of intracerebroventricularly administered alpha 1-adrenoceptor agonists in the conscious rat

To determine the interaction between central adrenergic and vasopressinergic mechanisms in the regulation of cardiovascular function, the effects of intracerebroventricular (i.c.v.) administration of the alpha 1-agonists, methoxamine and phenylephrine, in conscious Long-Evans (LE) rats were compared with those in Brattleboro rats with hereditary hypothalamic diabetes insipidus (DI). In LE rats, both i.c.v. methoxamine and phenylephrine increased mean arterial pressure (MAP) and decreased heart rate (HR) in a dose-related manner, while they had no effect on MAP and HR in DI rats within the dose range of 3-30 micrograms/kg. Both i.c.v. methoxamine (10 micrograms/kg) and phenylephrine (30 micrograms/kg) also increased plasma levels of arginine vasopressin (AVP) in LE rats from 2.6 +/- 0.4 (n = 9) to 22.4 +/- 3.5 (n = 6, P less than 0.01) and 37.0 +/- 4.0 pg/ml (n = 6, P less than 0.01), respectively, without affecting plasma renin activity (PRA) and plasma angiotensin II (ANG II) levels. Central alpha 1-adrenoceptor stimulation increases vasopressin release from the posterior pituitary, which in part is responsible for the hypertensive and bradycardic responses. However, central vasopressinergic pathways have also been shown to be involved in these cardiovascular effects. Neither i.c.v. nor intravenous (i.v.) infusion of AVP restored the cardiovascular response to i.c.v. alpha 1-agonists in DI rats. In LE rats, however, i.v. pretreatment with the specific vascular antagonist to the pressor effect of AVP, d(CH2)5Tyr(Me)AVP (VP-ANT; 10 micrograms/kg), significantly attenuated, but did not completely block the hypertensive and bradycardic effects of i.c.v. methoxamine and phenylephrine.(ABSTRACT TRUNCATED AT 250 WORDS)