Plasma renin activity and urinary kallikrein excretion in response to intravenous furosemide in diabetic patients

Summary The responsiveness of renin-angiotensin and kallikrein-kinin systems to furosemide challenge has been investigated in forty-six diabetic patients (34 NIDDM/12 IDDM), subdivided into Group I (uncomplicated DM), Group II (DM with hypertension), Group III (DM with nephropathy), Group IV (DM with hypertension and nephropathy) and a control group of 10 healthy volunteers. Plasma renin activity (PRA) was estimated by radioimmunoassay in blood samples drawn before and 10 min after furosemide administration (0.5 mg/kg i.v.). Urinary kallikrein levels were measured by bioassay using estrogenized rat uterus preparation in 4h urine samples collected before and after the diuretic. Urinary Na⁺ and K⁺ were also measured. The basal PRA in diabetics was not significantly different from controls, whereas, urinary kallikrein levels were markedly low in all patients. Both PRA and kallikrein levels increased after furosemide in controls while in diabetics this response was severely blunted. In a subset of Group I, a paradoxical fall in PRA and kallikrein levels was noted after furosemide, an effect similar to that observed in patients with nephropathy (Group III). This response in absence of clinical and biochemical parameters of nephropathy indicates early derangement of renal hemodynamic mechanisms heralding the onset of nephropathy.     

氯沙坦及氯沙坦与双氢克尿噻合剂对原发性高血压患者肾素活性影响的比较

目的比较血管紧张素Ⅱ受体拮抗剂氯沙坦及氯沙坦与双氢克尿噻合剂对原发性高血压患者的降压疗效和肾素活性水平的影响。 方法坐位舒张压95～115mmHg(1mmHg=0.133kPa)的76例原发性高血压患者,经1周药物洗脱期,2周安慰剂期后,随机服用氯沙坦50mg(氯沙坦组,n=37),每日1次或氯沙坦50mg与双氢克尿噻12.5mg合剂(氯沙坦+双氢克尿噻合剂组,n=39),每日1次。4周末坐位舒张压≥90mmHg者,剂量分别加倍,继续服用4周。于安慰剂期末及服药8周末测量诊室坐位血压和测定立位血浆肾素活性水平。 结果服药8周末平均坐位舒张压氯沙坦组(n=35)下降10.1±9.1mmHg;氯沙坦+双氢克尿噻合剂组(n=33)下降14.6±7.5mmHg(组间比较P＜0.05);同时服用末次药24小时后氯沙坦组的平均血浆肾素活性从1.6ng/(ml*h)增加至5.4ng/(ml     

Renal kallikrein in diabetic patients with hypertension accompanied by nephropathy

Summary We measured the 24-h excretion of urinary kallikrein in 27 patients with Type 2 (non-insulin-dependent) diabetes and in 10 normal control subjects. Mean (± SD) kallikrein excretion in diabetic patients with nephropathy (6.2±2.4 naphthyl units (NU)/day,n=13) was significantly lower than in control subjects (12.8±3.4NU/day,p<0.01) and in diabetic patients without nephropathy (9.4±3.4NU/day,n=14,p<0.05). Kallikrein excretion in hypertensive diabetic patients with nephropathy (5.1±1.6 NU/day,n=8) was significantly lower (p<0.05) than in normotensive patients with nephropathy (8.3±2.1 NU/day,n=5). There were no significant differences in kallikrein excretion rate (24-h excretion of urinary kallikrein/24-h creatinine clearance) among control subjects (9.9±4.3 NU/ml), diabetic patients with (9.0±3.2 NU/ml) and without (9.3±3.5 NU/ml) nephropathy. However, kallikrein excretion rate in hypertensive diabetic patients with nephropathy (7.7±3.3 NU/ml) was significantly lower (p<0.05) than in normotensive diabetic patients with nephropathy (11.8 ±2.0 NU/ml,n=10). Respective basal and post-stimulated (with intravenous furosemide 40 mg plus 60 min ambulation) plasma aldosterone concentrations measured in control subjects and in hypertensive diabetic patients with nephropathy were similar and increased to the same extent in the 2 groups (5.5±3.2 versus 5.3±3.2 and 9.3±2.6 versus 10.5±3.4 ng/ml), although the respective plasma renin activity tended to be lower in diabetic patients than in control subjects (0.7±0.6 versus 1.3±0.9 and 1.8±1.8 versus 3.0±2.6 ng⁻¹ · ml⁻¹ · h⁻¹). The results indicate that urinary kallikrein excretion is decreased in hypertensive diabetic patients with nephropathy, and that the decrease might not be attributable to an altered renin-aldosterone system.     

Single Oral Administration of Captopril may not bring an Improvement in Screening of Primary Aldosteronism

Plasma renin activity (PRA) and plasma aldosterone concentration (PAC) were measured in 19 cases with primary aldosteronism (PA) and 72 with essential hypertension (EHT) to differentiate the two disorders in the following conditions: 1) after overnight recumbency (basal state) and 2) after oral administration of captopril. Screening criteria were determined in order to pick up all of PA patients as positive. After the captopril administration, the specificity of a criterion based on the combination of PAC and PAC/PRA ratio was 93 % and positive predictive value 79 %. This criterion was superior to other conventional screening methods. However, higher specificity (97 %) and positive predictive value (90 %) were obtained from a combination criterion based on the basal PAC and PAC/PRA ratio. The single oral administration of captopril may not bring an improvement in the screening of PA.     

Urinary Excretion of Renal Prostaglandins,Kallikrein, Vasopressin and Aldosterone in Essential Hypertension

To assess the relationship between pressor and depressor factors in essential hypertension, the urinary excretion rates of prostaglandins E2 and F2α, kallikrein, vasopressin and aldosterone were compared between 53 untreated hypertensive patients and 53 age- and sex-matched normotensive controls. Mean basal levels of plasma renin activity and of urinary prostaglandins, vasopressin and aldosterone were similar in both groups, but urinary kallikrein was significantly lower in the hypertensive patients. A weak relationship was found in the hypertensives between diastolic blood pressure, and vasopressin or aldosterone, and between vasopressin and prostaglandin E2, and in the normotensives between vasopressin and prostaglandin F2α. In conclusion, these results do not provide evidence for an important imbalance between pressor and depressor factors in essential hypertension, as reflected by the urinary excretion of the major humoral factors and hormones involved in the regulation of blood pressure.     

醛固酮合酶基因多态性与原发性高血压及血浆醛固酮水平的关系

目的　探索武汉地区汉族人群中醛固酮合酶 (CYP11B2 )基因 3 44C/T多态性与原发性高血压 (EH)的相关性 ,及高血压人群醛固酮合酶CYP11B2基因 3 44C/T多态性与血浆醛固酮(pAldo)水平的相关性。方法　应用PCR RELP技术对 2 0 4例CYP11B2基因 3 44C/T多态性进行分析 ,应用放射免疫法测定 10 6例EH组的血浆醛固酮水平。结果　CYP11B2基因 3 44C/T多态性以TT和CT为主要基因型 ,与EH无明显相关性 (P >0 .0 5 )。高血压患者血浆醛固酮水平在CYP11B2基因 3 44C/T的 3个不同基因型组比较差异有显著性 (P <0 .0 1)。结论　武汉地区汉族人群CYP11B2基因 3 44C/T多态性频率与EH没有明显相关性。高血压人群的血浆醛固酮水平与CYP11B2基因 3 44C/T多态性相关     

The Utility of Renin Profiling in Childhood Hypertension

Criteria to categorize children as having hypertension associated with high, low or normal PRA as determined by the technique of renin sodium indexing; or with PRA responsiveness which was normal, suppressed or excessive after acute volume depletion induced by a loop diuretic were established in 30 normotensive adolescents. Four hour upright PRA corrected for daily sodium excretion was elevated in 16% of 43 and 84% of 25 children with essential and renal related hypertension. Low PRA was found in 5 of 43 and 0 of 25 children. In 36 children with essential hypertension evaluated after acute volume depletion, 4 and 5 had hyperand hypo- responsive PRA compared to the 30 normotensive children. The application of these two approaches enables the renin angiotensin system to be systematically categorized in hypertensive children.     

Hypertension in Hypothyroidism: Arterial Pressure and Hormone Relationships

To investigate the regulation of arterial pressure and vaso-active hormones in hypothyroidism associated with hypertension, we measured intra-arterial pressure and hourly venous hormones (renin, angiotensin II, aldosterone, catecholamines and cortisol) for 24 hours in five hypertensive patients with primary hypothyroidism before commencing treatment, and again after three to six months of thyroxine replacement therapy. Arterial pressure fell significantly after thyroxine replacement in four patients. Thyroxine treatment was associated with a fall in plasma norepinephrine levels together with a decline in slopes of norepinephrine/arterial pressure regression lines which suggests that the sympathetic system may contribute to the hypertension in hypothyroidism. Variability of heart rate, blood pressure and plasma norepinephrine fell with thyroxine replacement consistent with impaired damping of swings in sympathetic activity in the untreated state. Reciprocal changes in arterial pressure and renin-angiotensin-aldosterone system activity suggested that this system was not the mediator of hypertension in hypothyroidism.     

45岁及以上高血压患者醛固酮与颈动脉粥样硬化关系研究

目的探讨45岁以上高血压患者血清醛固酮浓度(PAC)与颈动脉粥样硬化(CA)的关系。方法连续入选新疆维吾尔自治区人民医院高血压中心住院的45岁以上高血压患者126例,根据颈动脉超声检查结果分为CA组(74例)和无CA组(52例)。测定患者常规及分别立、坐、卧2 h后的PAC。用简单相关分析两组双侧颈动脉内膜中层厚度(IMT)与常规及三体位的PAC相关性。采用Logistic回归分析CA与常规及三体位的PAC关系。结果 CA组的常规PAC(rs=0.361,P=0.003)与双侧颈内动脉IMT均值呈正相关;Logistic回归分析显示,校正了年龄、性别、高血压病程、吸烟、饮酒、血压升高程度、糖尿病及脂质代谢紊乱等相关混杂因素后,坐位PAC(OR=1.126,95%CI1.005～1.261,P=0.04)、常规PAC(OR=1.147,95%CI 1.008～1.304,P=0.037)与CA独立相关。结论坐位及常规PAC可能是CA形成的独立危险因素。     

高血压患者不同体位血浆醛固酮浓度与颈动脉粥样硬化的关系

目的探讨立、坐、卧三体位血浆醛固酮浓度及立、卧位差值与颈动脉粥样硬化(CA)的关系。方法入选在新疆自治区人民医院高血压科住院的高血压患者252例,并进行体位实验。根据颈动脉超声检查结果将252例患者分为斑块组(80例)和无斑块组(172例)。测定入选患者立、坐、卧三体位的血浆醛固酮水平。用Spearman等级相关分别分析两组双侧颈动脉内膜中层厚度(IMT)均值与不同体位的醛固酮及立卧位醛固酮差值的相关性。采用Logistic回归分析CA与立、坐、卧三体位的醛固酮及立卧位醛固酮差值的关系。结果斑块组的立位醛固酮(rs=0.237,P=0.041)、立卧位醛固酮差值(rs=0.262,P=0.023)与双侧颈总动脉IMT均值呈正相关;Logistic回归分析显示,校正了相关混杂因素后,立位醛固酮与CA独立相关(OR=1.22,95%CI1.09～2.38,P=0.028)。结论立位醛固酮水平与高血压患者CA相关。     

Hormonal effects of the diuretic xipamide in healthy men

The effect of xipamide on plasma alpha-atrial natriuretic peptide and the renin-aldosterone-kallikrein system have been studied in 12 healthy men, using a double-blind cross-over design. After a run-in period on placebo of 1 week, the subjects were treated with either placebo (n = 6) or xipamide 20 mg once daily (n = 6) for 16 weeks and were then switched to the alternative medication for another 16 weeks. The plasma concentration of alpha-atrial natriuretic peptide fell after 1 week of xipamide administration and increased during prolonged xipamide administration but remained reduced. The changes in plasma alpha-ANP observed after 1 week of xipamide were negatively correlated with the changes in hematocrit and hemoglobin. Plasma renin activity (PRA), aldosterone concentration (PAC), and urinary excretion of aldosterone and kallikrein increased after 1 week of xipamide administration, levelled off during the second and fourth weeks, but remained elevated during further prolonged xipamide administration for 16 weeks. The xipamide-induced changes in PRA and PAC were positively correlated with the changes in the hematocrit and hemoglobin. The changes in plasma renin, aldosterone, and alpha-atrial natriuretic peptide during xipamide administration may be related to diuretic-induced volume contraction.     

Nocturnal diastolic blood pressure decline is associated with higher 25-hydroxyvitamin D level and standing plasma renin activity in a hypertensive population

Patients with nondipper hypertension are known to carry a high risk of cardiovascular complications. Vitamin D deficiency is associated with hypertension. Because vitamin D deficiency activates the renin–angiotensin–aldosterone system (RAAS), we hypothesized that this vitamin would interact with the RAAS to influence blood pressure (BP) in nondipper hypertensive patients. We performed a cross-sectional analysis of 1,007 outpatients with hypertension (HTN). Dipper and nondipper patterns were detected, and the two groups were matched for clinical, laboratory, 25-hydroxyvitamin D (25OHD) levels, and ambulatory blood pressure recording. Plasma renin activity (PRA), angiotensin II, and plasma aldosterone concentration (PAC) were assessed in 174 patients treated with calcium channel blockers or no medication. The mean 25OHD concentration in the entire study population was 12.3ng/dL, and the prevalence of vitamin D deficiency was 87.0%. Dipper and nondipper HTN were noted in 187 patients (24.6%) and 573 patients (75.4%). 25OHD levels were similar between nondipper and dipper HTN groups. Forward stepwise logistic regression analysis showed that BMI and age were independent predictors of nondipper HTN. Neither 25OHD levels nor RAAS components were included in the model. In correlation analyses, nocturnal decline of diastolic BP was positively associated with 25OHD levels and standing PRA (r = 0.152 p = 0.045, r = 0.165 p = 0.038, respectively). The present study showed that vitamin D deficiency was astonishingly prevalent in hypertensive subjects residing in Xinjiang, China. There may be a weakly association of nocturnal DBP decline with 25OHD levels and standing PRA levels. We found no association between vitamin D deficiency and nondipper HTN.     

Association Between Increased Plasma Levels of Aldosterone and Decreased Systemic Arterial Compliance in Subjects With Essential Hypertension

We previously observed that, in subjects with essential hypertension, acute ouabain constricts the brachial artery diameter in the presence of spironolactone treatment, a finding that is not observed in the absence of aldosterone antagonist and therefore suggests a specific effect of aldosterone on the arterial wall. To evaluate whether aldosterone excess may contribute to modulate arterial function, we investigated 56 patients with sustained essential hypertension in comparison with 36 normotensive controls. Systemic arterial compliance was measured from intraarterial blood pressure and cardiac output measurements using a classical Windkessel model to determine the elasticity of the proximal arterial tree. Radial artery compliance was determined using a previously described echo tracking technique. In hypertensive, but not in normotensive, subjects, systemic arterial compliance was strongly and negatively correlated with plasma aldosterone. The correlation was observed even after adjustment for age and blood pressure. Plasma potassium and renin activity did not interfere in the correlation. Acute administration of diltiazem did not change systemic compliance but significantly decreased plasma aldosterone, suggesting that, in the presence of calcium blockade, the same compliance was achieved for a lower plasma aldosterone level. Taken together, these findings strongly suggest that significant interactions exist between aldosterone and central conduit arteries and that aldosterone might modulate arterial function in subjects with essential hypertension.     

Relation Between Night Urinary Free Cortisol and Hypertension in Youth

Objectives To study the relation between night urinary free cortisol (UFC) excretion and hypertension in youth. Methods Night urinary free cortisol excretion and blood pressure & its related factor were measured in 188 young people. Results In young men with hypertension the 8 h's night UFC excretion was significantly higher than that in the group with normal blood pressure 21. 57±6. 28μg/8 h vs 10. 54 ± 5. 46 μg/8 h ( P < 0. 05) . In a group of young people with positive family history of hypertension, the night UFC excretion was much higher than that in the group with negative family history of hypertension. Men excrete much more night UFC than women (12. 73 ± 5. 85 μg/8 h vs 7. 80 ± 4. 15 μg/8 h, P < 0. 05). Conclusions There is an association between hypertension and high 8h's night UFC excretion; furthermore, there is gender difference in night UFC excretion.     

肾脏局部肾素-血管紧张素系统与血压昼夜节律的关系研究

目的 探讨肾脏局部肾素-血管紧张素系统(RAS)是否存在昼夜节律,及其与血压昼夜节律的关系.方法 选择2018年3月至2019年3月在河北省人民医院就诊的原发性高血压(EH)患者104例,其血清肌酐(SCr)与估算的肾小球滤过率(eGFR)均正常.根据收缩压的昼夜节律类型,将患者分为杓型组37例、非杓型组35例和反杓型...     

Dissociation of Plasma Atrial Natriuretic Peptide Responses to Upright Posture and Furosemide Administration in Patients with Normal-, Low Renin Essential Hypertension and Primary Aldosteronism

Plasma levels of atrial natriuretic peptide (ANP) were measured in patients with normal renin essential hypertension (n = 12), low renin essential hypertension (n = 11) and primary aldosteronism due to aldosterone producing adenoma (APA, n = 8) and idiopathic hyperaldosteronism (IHA, n = 3) after overnight rest in the supine position and after 4 h upright posture and furosemide administration. Plasma renin activity (PRA) and aldosterone (Aldo) levels were also determined. Compared to normal renin essential hypertension (33.6± 2.2 pg/ml), basal plasma ANP was significantly higher in low renin essential hypertension (66.8± 6 pg/ml), IHA (54.1± 6.3 pg/ml) and APA before (62.4± 4.9 pg/ml) but not after adrenal surgery (22± 3 pg/ml). After upright posture and furosemide administration plasma ANP was decreased (p < 0.01) in patients with low renin and, less markedly, with normal renin essential hypertension, however not in IHA and APA. In about half of the patients with low renin essential hypertension, unchanged PRA after upright posture and furosemide administration was associated with increased plasma Aldo and decreased ANP levels. We conclude that (i) the relatively high basal plasma ANP levels in low renin essential hypertension, IHA and APA may reflect the presence of volume expansion in these patients; (ii) the hormonal responses to upright posture and furosemide administration in patients with normal and low renin essential hypertension may indicate a counterregulatory role of ANP during activation of the renin-angiotensin-aldosterone system; (iii) the high plasma ANP, which is unresponsive to upright posture and furosemide administration, in patients with APA and IHA may be a potentially interesting new finding whose pathophysiological significance remains to be established.     

高血压与糖尿病患者尿铜蓝蛋白排泄率的变化比较

了解血管损伤性疾病高血压、糖尿病患者尿铜蓝蛋白与尿白蛋白排泄率的变化并进行比较 ,评价其临床意义。用酶联免疫吸附测定法检测尿中铜蓝蛋白及尿白蛋白水平。结果 10 7例正常人尿铜蓝蛋白排泄率为 5 2 .98± 32 .89ng min ,尿白蛋白排泄率为 7.13± 2 .2 9μg min ;4 5例高血压患者尿铜蓝蛋白排泄率为 94 .0 1± 6 9.5 0ng min ,尿白蛋白排泄率为 10 .4 2± 8.19μg min ;112例糖尿病患者尿铜蓝蛋白排泄率为 131.92± 10 3.6 4ng min ,尿白蛋白排泄率为 18.6 9± 2 7.30 μg min。对以上资料分别与正常对照组进行比较 ,统计分析结果表明 ,尿铜蓝蛋白排泄率在各组间差异非常显著 (P <0 .0 5 )。糖尿病患者尿铜蓝蛋白排泄率比高血压患者尿铜蓝蛋白排泄率更高。高血压、糖尿病常伴有肾小球血管内膜损伤 ,因肾小管基底膜电荷改变 ,网孔变大 ,使带电荷铜蓝蛋白经该处大量逸出。提示尿铜蓝蛋白排泄率对高血压、糖尿病病情监测有重要的临床意义     

青年夜尿游离皮质醇与原发性高血压的关系

目的 :研究青年夜尿游离皮质醇的排泄量与原发性高血压的关系。方法 :对 188名青年进行血压及相关因素、夜 8小时尿游离皮质醇的测定。结果 :青年男性原发性高血压者夜 8小时尿游离皮质醇的排泄量显著高于血压正常者 ( 2 1 5 7± 6 2 8μg/8h对 10 5 4± 5 46μg/8h ,P <0 0 5 ) ;高血压家族史阳性者显著高于高血压家族史阴性者 ,在男、女性中分别为 16 90± 6 5 0 μg/8h对 9 44± 4 95 μg/8h(P <0 0 5 ) ,10 5 4± 5 46μg/8h对 6 2 2± 3 18μg/8h(P <0 0 5 ) ;男性明显高于女性 ,12 73± 5 85μg/8h对 7 80± 4 15 μg/8h(P <0 0 5 )。结论 :青年男性高血压者夜 8小时尿游离皮质醇的排泄量明显高于血压正常者 ,夜尿游离皮质醇的排泄量与高血压的家族史相关联 ,且存在明显的性别差异。提示青年高血压患者及其易感者中已存在皮质醇代谢的异常 ,糖皮质激素可能参与高血压的发病过程。     

高血压患者血清磷酯脂肪酸谱与血脂的相关性研究

目的研究高血压患者血清磷酯脂肪酸谱与血脂的相关性。方法采用高效气相色谱法测定高血压患者和健康对照者的血清磷酯脂肪酸谱,酶法测定血脂。结果高血压组的14:0、16:0、18:0和饱和脂肪酸(SFA)较对照组显著升高,16:1、18:1、18:2n-6、20:5n-3、单不饱和脂肪酸(MUFA)、n-6多不饱和脂肪酸(n-6 PUFA)、n-3多不饱和脂肪酸(n-3 PUFA)和多不饱和脂肪酸(PUFA)较对照组显著降低。总胆固醇(TC)与18:0正相关,而与16:1和18:1负相关;甘油三酯(TG)与18:2n-6、20:5n-3、和PUFA负相关;高密度脂蛋白胆固醇(HDL-C)与)18:2n-6、20:4n-6和n-6PUFA正相关;低密度脂蛋白胆固醇(LDL-C)与14:0和16:0正相关,而与n-3PUFA负相关。结论高血压血清磷酯脂肪酸谱中SFA高于健康对照,MUFA和PU-FA低于健康对照。而与血脂的相关分析显示SFA与高血压的血脂升高有关,而MUFA和PUFA对高血压患者的血脂具有保护作用。