原发性高血压和妊娠高血压患者血清中钠泵抑制因子免疫活性物的测定

目的为了探讨内源性Na+/K+-ATP酶(钠泵)抑制因子水平与高血压发病之间的关系.方法我们检测了原发性高血压患者48例,正常血压者35例;妊娠高血压患者15例,正常孕妇20例采用反相C18预柱处理及酶联免疫吸附法(ELISA)测定血清中哇巴因样物质(OLC)和前海葱苷原A样物质(PLC)水平.结果原发性高血压患者血清中OLC水平为132±21 pmol/L,PLC水平为5.85±2.59 pmol/L,分别明显高于正常人16.4±5.2 pmol/L和0.42±0.20 pmol/L(P<0.001);妊娠高血压患者血清中OLC和PLC水平分别为34.6±11.12 pmol/L和10.2±5.05 pmol/L,明显高于正常孕妇3.8±0.86 pmol/L和1.2±0.14 pmol/L(P<0.001).结论证明高血压患者血液中的内源性钠泵抑制因子水平升高可能是高血压发病的重要因素之一.     

连续性肾脏替代疗法对多器官功能障碍综合征患者血浆白介素6、10水平的影响

目的观察多器官功能障碍综合征(MODS)患者采用连续性肾脏替代疗法(CRRT)治疗0h,8h,24h和48h后肾功能及血浆白介素6(IL-6)、IL-10水平变化,探讨CRRT治疗MODS的可能机制。方法用CRRT方法治疗MODS患者71例,观察CRRT治疗前及治疗8h、24h和48h后患者肾功能及血浆IL-6、IL-10水平变化。结果MODS患者除尿素氮(BUN)和血肌酐(SCr)异常外,其血浆IL-6和IL-10水平均较正常对照组高(P均<0.01),CRRT治疗8h,24h和48h后MODS患者肾功能得到明显改善的同时[BUN0h/(26.15±13.60),8h/(19.45±8.63),24h/(17.22±6.11),48h/(16.36±7.86)mmol/L,与CRRT0h比较均P<0.01;SCr0h/(552.63±348.44),8h/(386.95±231.96),24h/(328.19±106.53),48h/(369.38±222.98)μmol/L,与CRRT0h比较均P<0.01)],患者血浆IL-6水平较治疗前明显降低[0h/(469.44±288.75),8h/(386.95±231.96),24h/(398.45±98.89),48h/(316.89±60.70)ng/ml,CRRT48h与0h比较P<0.05;而血浆IL-10水平较治疗前明显升高0h/(3.34±2.12),8h/(3.18±1.88),24h/(5.87±4.77),48h/(7.71±5.23)ng/ml)],CRRT24h、48h与0h比较P<0.05。结论CRRT是MODS的有效治疗方法,提示有效清除体内的代谢产物和炎性介质是CRRT治疗MODS的可能机制。     

普伐他汀早期应用对急性冠状动脉综合征血管炎症反应及内皮功能的影响

目的观察普伐他汀在急性冠状动脉综合征患者早期(发病48h以内)应用对患者血浆一氧化氮、内皮素及C反应蛋白的影响。方法60例急性冠状动脉综合征患者随机分为两组。普伐他汀组30例,常规治疗组(未服用他汀类调脂药物)30例,疗程2周,分别于治疗前后测定血浆一氧化氮、内皮素及C反应蛋白水平。结果普伐他汀组血浆C反应蛋白(32.7±10.8μg/L)及内皮素(50.3±17.2μg/L)水平明显下降、血浆一氧化氮(50.3±10.2μmol/L)水平明显上升,与常规治疗组血浆C反应蛋白(44.3±9.7μg/L)、内皮素(72.4±16.4μg/L)及血浆一氧化氮(42.8±8.7μmol/L)水平比较有显著性差异(P<0.01)。结论普伐他汀在急性冠状动脉综合征患者中早期应用能够抑制血管内皮的炎症反应,稳定粥样斑块,改善血管内皮功能,解除冠状动脉痉挛。     

高血压病人不同左室功能与血浆B型钠尿肽及Ⅲ型前胶原的关系

目的探讨原发性高血压患者不同左心室功能状态与血浆B型钠尿肽(BNP)及血清Ⅲ型前胶原(PCⅢ)的相互关系。方法入选原发性高血压患者190例,根据心功能情况分为心功能正常、左室舒张功能不全、左室收缩功能不全三组,另设正常对照组40例,所有患者均行超声心动图检查。用放免法测定血清PCⅢ浓度,干式快速免疫荧光法定量测定血浆BNP浓度。结果(1)高血压患者心功能正常、左室舒张功能不全、左室收缩功能不全三组的BNP与PCⅢ水平分别为:49±18pg/ml,135±31pg/ml,283±96pg/ml;82.3±33.7ug/L,119.4±38.5ug/L,147.4±51.6ug/L;血压正常对照组BNP与PCⅢ水平分别为43±16pg/ml,77.5±23.1ug/L。BNP与PCⅢ水平在高血压患者三组间逐步增高(P<0.05),且以左室收缩功能不全组增高最显著(P<0.05);(2)血浆BNP水平与LVMI、血清PCⅢ水平均呈显著正相关(P<0.05)。结论血浆BNP及组织纤维化血清指标PCⅢ可客观反映高血压患者不同左心室功能状态。     

妊娠高血压患者的血浆促皮质素释放激素升高

妊娠高血压约占孕妇5%,是胎儿及母体发病与死亡率的一个主要原因。但其病因及启动机制尚未明,人类胎盘产生多种激素与下丘脑释放激素及垂体激素相似。妊娠高血压妇女的促皮质素释放激素(CRH)较正常妊娠者高。本文旨在了解妊娠高血压妇女的血浆CRH、ACTH,β-内啡肽与氢化可的松等浓度及其相互关系。病人和方法妊娠高血压妇女14例,年龄20～39岁,孕期32～39周。正常妊娠妇女20名,年龄相同,孕期30～39周作对照。14例收缩压为145～200mmHg,舒张压为90～120mmHg。其中9例同时有蛋白尿,0.5～3g/L。12例在孕期经治疗或产后2周血压恢复正常。结果病例组平均CRH为4257±840ng/L,明显高于对照组的1083±227ng/L(P<0.001)。而ACTH病例组为65.0±6.0ng/L,只稍高于对照组的50.7±2.5ng/L(P<0.025)。β-内啡肽、氢化可的松及人胎盘催乳素则两组差异不大。对照组的     

急性冠状动脉综合征患者血浆中妊娠相关蛋白酶-A及C反应蛋白的变化

目的　研究急性冠状动脉综合征 (ACS)患者血浆中妊娠相关蛋白酶 - A(PAPP- A)和超敏 C反应蛋白 (hs-CRP)的变化及两者之间关系。方法　 6 8例经冠状动脉造影证实的冠心病患者 ,其中 ACS4 3例 ,稳定型心绞痛(SAP) 2 5例 ,2 0例正常健康人为对照组。采用酶联免疫吸附法 (EL ISA)检测其血浆中 PAPP- A,采用超敏免疫透射比浊法测定血浆 hs- CRP水平。结果　 1ACS患者血浆中 PAPP- A和 hs- CRP浓度均显著高于对照组 [PAPP- A :(17.9± 8.7) m IU / L vs (7.1± 4 .2 ) m IU / L ,P<0 .0 1;hs- CRP:(4.31± 0 .38) mg/ L vs (2 .0 1± 0 .14 ) mg/ L ,P<0 .0 1]。 2 ACS患者血浆中 PAPP- A和 hs- CRP均较 SAP组显著增高 [PAPP- A:(17.9± 8.7) m IU / L vs (8.5±5 .6 ) m IU/ L,P<0 .0 1;hs- CRP:(4.31± 0 .38) m g/ L vs(2 .13± 0 .2 8) mg/ L,P<0 .0 5 ]。 3SAP患者与正常对照组之间 PAPP- A与 hs- CRP均无显著性差异 (P>0 .0 5 )。 4直线相关分析发现 hs- CRP与 PAPP- A之间有显著性相关 (r=0 .6 8,P<0 .0 1)。结论　 PAPP- A与 hs- CRP在 ACS患者血浆中均显著增高 ,可作为 ACS患者的诊断敏感性指标之一 ,且 hs- CRP与 PAPP- A之间存在显著相关性。     

高血压病患者血浆内皮素-1浓度的变化及氯沙坦干预的效果

目的:探讨内皮素—1在EH发生中的作用以及氯沙坦干预前、后EH患者内皮素—1水平的变化。方法:76例高血压患者眼用氯沙坦6周(剂量50～100mg/d),部分患者加用双氢氯噻嗪(12.5mg,2次/d),观察氯沙坦治疗前、后血压和血浆内皮素—1的变化。结果:EH组与对照组血浆内皮素—1水平分别为89.13±29.17ng/L、60.13±10.23ng/L,前者显著升高(P<0.05),高血压Ⅲ级者的ET-1水平显著高于高血压Ⅱ级的(P<0.05)。氯沙坦治疗前、后内皮素—1水平分别为89.13±29.17ng/L、65.32±7.19ng/L,治疗后的显著降低(P<0.01)。氯沙坦治疗前收缩压和舒张庄分别为168.34±12.92、112.46±6.09mmHg,治疗后分别为125.71±20.05、80.15±5.11mmHg,均较治疗前明显降低(P<0.01)。结论:内皮素—1在高血压的形成和维持中起者重要的作用,氯沙坦在有效降压时,可以降低血浆内皮素—1水平。     

阿托伐他汀对急性冠状动脉综合征患者血清C反应蛋白的影响

目的探讨阿托伐他汀对急性冠状动脉综合征患者血清C反应蛋白的影响。方法选择急性冠状动脉综合征患者46人,随机分为阿伐他汀组和常规治疗组,阿伐他汀组在常规治疗的基础上加用阿托伐他汀每天40mg,常规治疗组采用常规治疗。分别于治疗前和治疗后两周测定血清C反应蛋白和血脂水平,比较其差异。结果46例急性冠状动脉综合征患者中,不稳定心绞痛17例,急性心肌梗死29例。血清C反应蛋白水平,心绞痛者为1.37±0.52 g/L,心肌梗死者为2.23±0.45 g/L,均高于正常对照组的0.30±0.22 g/L(P<0.05),心肌梗死患者较心绞痛者C反应蛋白升高显著(P<0.05)。阿托伐他汀治疗两周,血清C反应蛋白水平由1.88±0.45 g/L降至0.52±0.22 g/L,治疗前后相比有显著性差异(P<0.05)。常规治疗组血清C反应蛋白水平由1.85±0.50 g/L降至1.77±0.60 g/L,治疗前后相比无显著性差异(P>0.05)。结论C反应蛋白可能参与动脉粥样硬化的形成,短期使用阿托伐他汀即能明显降低急性冠状动脉综合征患者的血浆C反应蛋白水平,提示阿托伐他汀调脂作用之外还有抗炎作用。     

原发性高血压病患者血浆中钠泵抑制因子水平升高的直接证据

本文报告了正常人和原发性高血压病患者血浆中钠泵抑制因子的水平。正常对照组(35例)平均值为42.08±8.86U/L 血浆:高血压病组(42例)平均值为350.12±85.91U/L 血浆。两组间具有显著性统计学差异(P<0.001)。结果提示,钠泵抑制因子水平升高与原发性高血压病之间可能存在着因果关系。     

血清胱抑素C在妊娠期高血压早期肾损害中的意义

目的评价血清胱抑素C(CysC)在妊娠期高血压(GH)早期肾损害中的意义。方法收集GH患者40例、正常妊娠妇女70例(其中早中期妊娠35例,晚期妊娠35例)和30例正常对照者血清,以颗粒增强散射比浊法测定CysC、β2微球蛋白(β2-M),以生化分析法测定尿素氮(BUN)、血肌酐(SCr)、尿酸(UA)含量,并加以比较。结果正常血压晚期妊娠组(1.22±0.19)mg/L与GH组(1.93±0.48)mg/L的CysC水平均明显高于健康体检组[(0.78±0.22)mg/L,P<0.05和P<0.01];同时,GH组CysC水平高于正常血压晚期妊娠组(P<0.05);正常早中期妊娠组CysC水平与正常对照组无明显差异;GH组CysC水平与UA呈正相关(r=0.46,P<0.05)。结论血清CysC是评价妊娠期高血压早期肾功能损害的一项敏感和可靠的指标。     

Atrial natriuretic factor in pregnancy-induced hypertension and preeclampsia: increased plasma concentrations possibly explaining these hypovolemic states with paradoxical hyporeninism

Plasma immunoreactive atrial natriuretic factor 99-126 (ir ANF), plasma volume, plasma renin activity, and plasma aldosterone were measured during pregnancy in 14 normotensive nonpregnant women, 15 normotensive pregnant women, 35 patients with pregnancy-induced hypertension (PIH), and in ten patients with preeclampsia (PE). Repeated measurements were carried out 2 months after delivery in a subgroup of the same patients. The plasma levels of ANF were found to be higher in pregnant normotensive women than in nonpregnant normotensive women, but the decrease of plasma ANF 2 months after delivery was not significant on the basis of seven paired data, so that it cannot presently be stated with certainty that pregnancy per se stimulates ANF secretion. Still higher levels of ANF were found in PIH and, especially, in PE. A positive correlation was found in the pooled population of normotensive and hypertensive pregnant women between plasma ANF and mean arterial pressure. A greater decrease of plasma ANF was found after delivery in the hypertensive patients than in the normotensive controls. This excludes an absolute deficiency of ANF secretion in the pathogenesis of hypertension. These findings suggest a compensatory role of ANF in the prevention of blood pressure increase. Plasma renin activity (PRA) and plasma aldosterone concentrations were higher in normotensive pregnant women than in normotensive nonpregnant women. Compared to normal pregnancy, plasma volume was decreased in PIH (-17%) and in PE (-25%), whereas PRA was less increased in both groups and plasma aldosterone concentration was less increased only in the PE group. The simultaneous high levels of plasma ANF may explain this inappropriate hypostimulation of renin secretion by hypovolemia in these hypertensive states.     

大剂量阿托伐他汀对急性冠状动脉综合征患者血清抗氧化能力的影响

目的探讨大剂量阿托伐他汀对急性冠状动脉综合征患者血清抗氧化能力的影响。方法168例急性冠状动脉综合征患者随机分为大剂量阿托伐他汀治疗组和小剂量阿托伐他汀治疗组,分别检测治疗前、治疗1周和治疗2周后血清超氧化物歧化酶、谷胱甘肽过氧化物酶和丙二醛的含量;同时选择健康体检者50例作为正常对照组。结果急性冠状动脉综合征患者血清超氧化物歧化酶和谷胱甘肽过氧化物酶含量明显低于正常对照组(P<0.01),血清丙二醛含量明显高于对照组(P<0.01)。小剂量阿托伐他汀治疗组血清超氧化物歧化酶、谷胱甘肽过氧化物酶和丙二醛含量在阿托伐他汀治疗1周后无明显变化(P>0.05),治疗2周后血清超氧化物歧化酶和谷胱甘肽过氧化物酶含量开始升高(P<0.05),丙二醛开始下降(P<0.01)。大剂量阿托伐他汀治疗组在阿托伐他汀治疗1周时血清超氧化物歧化酶和谷胱甘肽过氧化物酶含量升高(P<0.05)、丙二醛含量明显降低(P<0.01),治疗2周后超氧化物歧化酶和谷胱甘肽过氧化物酶继续升高(P<0.05),丙二醛继续下降(P<0.01);且其血清超氧化物歧化酶和谷胱甘肽过氧化物酶含量升高幅度和丙二醛下降幅度均大于小剂量阿托伐他汀治疗组。结论短期大剂量阿托伐他汀能提高急性冠状动脉综合征患者血清的抗氧化能力。     

Cholecystokinin in acute alcoholic and biliary pancreatitis

Summary Background. Recent studies have shown that cholecystokinin (CCK) agonist, cerulein can induce acute pancreatitis in animals. The role of CCK in the induction of acute pancreatitis in humans is unclear. We investigated plasma CCK levels in alcoholic and biliary pancreatitis on admission and during the episode of acute pancreatitis. Methods. Plasma CCK concentrations were determined by a specific and sensitive radioimmunoassay using CCK antiserum (Euro-Diagnostica, Malm?, Sweden) in 35 patients with acute alcoholic pancreatitis, in 27 patients with acute biliary pancreatitis, in 34 patients with nonpancreatic acute abdominal pain, and in 43 healthy subjects. The mean time from the first symptoms to the plasma sample was 31 (±3.7) h in alcoholic pancreatitis patients and 25 (±5.1) h in biliary pancreatitis patients. We also determined CCK levels in 20 patients during the episode of acute pancreatitis. Normal fasting level of CCK is ≤1.12 pmol/L according to manufacturer. Results. Basal plasma CCK concentrations were significantly lower both in alcoholic pancreatitis (mean ± SEM, 0.04±0.03 pmol/L, p<0.0001) and biliary pancreatitis patients (0.17±0.13 pmol/L, p<0.0001) than in nonpancreatic acute abdominal pain patients (1.23±0.32 pmol/L) or healthy subjects (1.18±0.20 pmol/L). Plasma CCK levels also remained low until the patient was well-recovering and had started oral diet. Conclusion. Basal plasma CCK concentrations are significantly decreased in acute alcoholic and biliary pancreatitis after the first day from the beginning of the symptoms until the patient was well-recovering.     

Angiotensin-(1-7) in normal and preeclamptic pregnancy

Angiotensin-(1–7) (Ang-[1–7]) is a bioactive component of the renin-angiotensin system, which has depressor, vasodilatory, and antihypertensive actions. In normal pregnancy, we questioned whether the known rise in plasma angiotensin II (Ang II) is counterbalanced by an increase in plasma Ang-(1–7) and whether Ang-(1–7) levels are decreased in preeclampsia and may thus be a factor involved in the development of hypertension. Nulliparous preeclamptic subjects, third-trimester normotensive pregnant subjects, and a nonpregnant group were enrolled (n=15/group). Preeclamptic subjects had no previous history of hypertension or renal, connective-tissue, or metabolic disease, but at the time of delivery had significant hypertension (159±3/98±3 mmHg) and ≥3+ proteinuria. Plasma Ang-(1–7) was increased by 51% in normal pregnancy (p<0.05). Plasma Ang I, Ang II, and renin activity were also significantly elevated in normal pregnancy. In preeclamptic subjects, Ang-(1–7) was significantly decreased (p<0.01) compared with normal pregnant subjects. All other components of the renin-angiotensin-aldosterone system, except serum angiotensin-converting enzyme, were reduced in preeclamptic subjects compared with normal pregnant subjects; only plasma Ang II remained elevated in preeclamptic compared with nonpregnant subjects. These studies demonstrate, for the first time, increased plasma Ang-(1–7) in normal pregnant subjects compared with nonpregnant subjects and decreased Ang-(1–7) in preeclamptic subjects compared with normal pregnant subjects. In preeclampsia the decreased plasma Ang-(1–7) in the presence of elevated Ang II is consistent with the development of hypertension.     

Atrial natriuretic peptide and plasma volume in pregnancy-induced hypertension.

Pregnancy-induced hypertension (PIH) is characterized by a relative decrease in plasma volume and renin and aldosterone concentrations as well as increased capillary permeability compared with normal pregnancy. As many of these features could be explained by the actions of atrial natriuretic peptide (ANP), we examined the relationship between plasma volume and plasma ANP in women with PIH and in normal third trimester pregnant women, and whether ANP responses to alterations in posture were intact in women with PIH. Basal plasma ANP measured after 20 min lateral recumbency in women with PIH was 24.0 (13.9, 33.1) pmol/L (median [25th, 75th percentile]), which was significantly greater than in normal pregnant women (9.9 [6.3, 16.0]), (P less than .05). Plasma ANP did not differ between those with and without proteinuria in the PIH group. Plasma volume was decreased in women with PIH (20.1 [19.0, 23.2] mL/cm) v 23.5 [21.4, 25.3], P less than .05). Plasma renin concentration but not plasma aldosterone concentration was also decreased significantly in women with PIH compared with normal pregnant women (P less than .001) and both were correlated negatively with plasma ANP. Following prolonged lateral recumbency, plasma ANP rose to 26.9 [19.1, 44.1] pmol/L in women with PIH (P less than .05), which was still significantly greater than in normal pregnant women (15.5 [6.7, 21.9] pmol/L) (P less than .05). In a subgroup of these subjects, 30 min head-up tilt decreased plasma ANP by 5.2 [0.9, 22.3] pmol/L in women with PIH and by 6.1 [2.2, 10.3] pmol/L in normal pregnant women, a nonsignificant difference.(ABSTRACT TRUNCATED AT 250 WORDS)     

Plasma and amniotic fluid immunoreactive neuropeptide-Y level changes during pregnancy, labor, and at parturition

This study was designed to determine the presence of and possible changes in plasma and amniotic fluid immunoreactive neuropeptide-Y (irNPY) levels in pregnant women during gestation and at parturition. We studied 127 healthy pregnant and 12 nonpregnant women. The peptide was extracted from plasma or amniotic fluid with a propanolformic acid mixture and measured by RIA. The mean plasma irNPY concentration in 15 pregnant women during the first trimester of gestation was 129 +/- 12 (+/- SE) pmol/L, compared to 40 +/- 8 pmol/L in nonpregnant women (p less than 0.01). The mean values were 144 +/- 13 and 156 +/- 24 pmol/L, respectively, in 15 pregnant women during the second trimester and 33 women during the third trimester. These values did not differ from that during the first trimester. Amniotic fluid irNPY levels were similar to those in plasma and did not vary among the 3 groups of women studied during the various trimesters of gestation. During labor, plasma irNPY levels progressively increased, reaching the highest levels at the most advanced stages of cervical dilatation (greater than 8 cm, 351 +/- 38 pmol/L) and at the time of vaginal delivery (416 +/- 73 pmol/L). Plasma irNPY levels then decreased significantly 2 h after vaginal delivery. The amniotic fluid irNPY levels in women during the early or late stages of labor were similar. Moreover, plasma and amniotic fluid irNPY levels at the time of elective cesarean section also were similar. These results indicate that pregnant women have high plasma and amniotic fluid irNPY levels and that the stress of labor results in a further increase in plasma levels, suggesting a possible role of NPY in human pregnancy and parturition.     

Mineralocorticoids and mineralocorticoid receptors in mononuclear leukocytes in patients with pregnancy-induced hypertension.

To examine the role of mineralocorticoids in the pathophysiology of pregnancy-induced hypertension (PIH), we studied plasma aldosterone and 18-hydroxycorticosterone levels in 25 women with PIH and 25 normal pregnant women, as controls. Furthermore, we evaluated the mineralocorticoid receptor (MR) status in mononuclear leukocytes in the 2 groups. MR count was significantly (P less than 0.0005) decreased in the PIH group (148 +/- 9 binding sites/cell) compared with the control group (300 +/- 17 binding sites/cell; mean +/- SEM). Plasma aldosterone in women with PIH was 281 +/- 61 pmol/L; in normal pregnant women it was 697 +/- 172 pmol/L (P less than 0.025). Plasma 18-hydroxycorticosterone was also significantly (P less than 0.025) lower (PIH, 1071 +/- 149 pmol/L; controls, 1907 +/- 318 pmol/L). These values were determined at the onset of clinical symptoms of PIH. These results cannot be explained by receptor down-regulation due to higher levels of mineralocorticoids in PIH; a hitherto unknown mineralocorticoid may, thus, be responsible for the hypertension and altered MR status.     

Follow up of patients with postpartum thyroiditis: a population-based study

In this survey we studied the prevalence of permanent hypothyroidism and prognostic factors for its occurrence 3–5 yr after postpartum thyroiditis (PPT); 54 of 120 women with PPT and 50 of 920 healthy women from among 1040 women followed 4–5 yr earlier for PPT were recalled. Demographic information, signs, and symptoms of thyroid disorders and results of physical exams were documented. Serum T₃, T₄, RT₃U, TSH, and antithyroperoxidase (antiTPO ab) and antithyrogluboline (antiTg ab) antibodies were measured. Twenty-two percent of the cases and four percent of the control group had permanent hypothyroidism, p<0.01. Based on the TSH level we divided the case group into two subgroups: PPT-Hypothyroidism (PPT-Hypo) and PPT-Eutyhroidism (PPT-EU); PPT-Hypo had greater titer of antiTPO ab than PPT-Eu (437±283 vs 126±221 IU/mL, p<0.001). Comparison of mean peak serum TSH level and antiTPO ab during the postpartum thyroiditis phase between PPT-Hypo and PPT-Eu in the case group was significant (56±24 vs 23±28 mU/L, p<0.001, and 1960±1270 vs 640±959 IU/L, p<0.001, respectively). Results of this survery show a high prevalence of permanent hypothyroidism following PPT in Tehran. High titers of antiTPOAb and TSH levels at postpartum period are prognostic factors for occurrence of permanent hypothyroidism.     

Endogenous Inhibition of Red Blood Cell Na,K-ATPase in Essential and Pregnancy-Induced Hypertension

Digoxin-like inhibitors of Na, K-ATPase have been implicated in the pathophysiology of essential(EH) and pregnancy-induced hypertension(PIH). A technique that enhances dissociation of digoxin from red blood cells(RBC) was used to displace endogenous digoxin-like substances from RBCs. RBC membranes were preincubated in Na and ATP(Release) or Na, K, Mg and ATP (Retention) prior to measuring ATPase activity. Groups studied were: 39 men with EH and 34 controls plus 10 women with PIH and 17 normotensive controls. All displayed similar increases in Na, K-ATPase activity (24.0±7.9%) following Release. Plasma digoxin immunoreactivity(DI) was measured in pregnant women, m= 0.25±0.07 ng/ml. No DI was detected in nonpregnant women, but RBCs from these women demonstrated the same increase in Na, K-ATPase activity after Release. The 24% increase in activity achieved by Na and ATP preincubation can be reversed by adding K and Mg to the Release suspension. However, after RBC-bound digoxin is displaced by Release preincubation, addition of K and Mg cannot promote renewed binding and pump inhibition. Thus, the observed endogenous inhibition is not due to displacement of a digoxin-like substance but probably is related to alteration of the enzyme-membrane interaction. Furthermore, even though pregnant women demonstrate DI, an inhibitory susbstance with digoxin-like binding could not be recognized using theis technique.     

Responses to corticotropin-releasing hormone and its bound and free forms in pregnant and nonpregnant women

Plasma CRH levels are considerably higher in women during the third trimester of pregnancy than in non-pregnant women. Most of plasma CRH in pregnant women is bound to CRH-binding protein (CRH-BP). To gain further insight into CRH physiology during pregnancy, we measured the responses of plasma ACTH and cortisol and the changes in bound and free forms of CRH in plasma after human CRH administration (2 micrograms/kg) in five pregnant (39-40 weeks of pregnancy) and five nonpregnant women. The mean basal plasma ACTH and cortisol levels in the pregnant women were higher than those in the nonpregnant women. However, the maximum increments in plasma ACTH and cortisol levels and the integrated ACTH and cortisol responses, after subtraction of the basal levels after CRH administration, were similar in the two groups. The plasma CRH half-time in the pregnant group was similar to that in the nonpregnant group. The mean basal plasma CRH level in the nonpregnant women was 1.5 +/- 0.2 (+/- SE) pmol/L, and that in the pregnant women was 360 +/- 35 pmol/L. On gel filtration chromatography, almost all of the CRH in the plasma was protein bound (320 +/- 30 pmol/L) in the pregnant women; no CRH peaks were detected in nonpregnant women because of the low plasma CRH levels. After CRH administration, the level of the bound form of plasma CRH was highest at 5 min, and then declined to a plateau at 15 min and 30 min in the pregnant women. In the nonpregnant women, protein-bound CRH also was highest at 5 min, but it progressively declined thereafter. The disappearance rate of the bound CRH in plasma from the nonpregnant women was similar to that of the second compartment of the plasma decay curves of the free CRH from both groups. We conclude that the plasma ACTH and cortisol responses to exogenous CRH are similar in pregnant and nonpregnant women, the effect of CRH-BP on the disappearance of plasma CRH is minimal, and plasma CRH-BP in pregnant women has the capacity to bind additional CRH.