Fluid balance in patients with chronic renal failure assessed with N‐terminal proatrial natriuretic peptide,atrial natriuretic peptide and ultrasonography

The N‐terminal proatrial natriuretic peptide (proANP) has become an important parameter for assessing the prognosis of patients with cardiac disease. Its use for evaluating the hydration status in patients with chronic renal failure, however, is still under investigation. The present study comprised 12 haemodialysis (HD) and 17 pre‐dialysis patients. In the HD patients, the inferior vena cava diameter during quiet expiration (IVCe) was estimated by ultrasonography and plasma concentrations of N‐terminal proANP, atrial natriuretic peptide (ANP) and cyclic guanosine monophosphate (cGMP) were measured before and 4 h after termination of HD. In the pre‐dialysis patients venous blood samples were taken during rest to measure plasma N‐terminal proANP and ANP and serum creatinine. Normal values for N‐terminal proANP and ANP were obtained from 18 healthy volunteers. The plasma concentrations of N‐terminal proANP and ANP in healthy volunteers were 328 ± 92 and 11.4.0 ± 3.1 p M L^?1, respectively. In pre‐dialysis patients, serum creatinine ranged from 110 to 447 μM L^?1 and was significantly correlated to plasma N‐terminal proANP (r=0.60, P < 0.05) but not to ANP. This may indicate that N‐terminal proANP is more dependent on renal function for its clearance than ANP, which is probably cleared by extrarenal mechanisms as well. In HD patients, IVCe was significantly correlated to the three hormones before HD, most strongly to N‐terminal proANP. After dialysis, IVCe was significantly correlated to ANP and cGMP but was not correlated to N‐terminal proANP. This may suggest that proANP takes a longer time than other hormones to reflect changes in intravascular volume. In conclusion, N‐terminal proANP is a hormone closely related to degree of renal function. Furthermore, it is a sensitive marker reflecting the interdialytic hydration status in HD patients, as indicated by its high correlation to IVCe, a standard method which is used frequently nowadays to assess the body hydration. However N‐terminal proANP could not reflect the acute changes in fluid volume induced by HD, probably because it is slowly metabolized.     

Effects of plasmapheresis on renal hemodynamics and sodium excretion in dogs

Summary Acute plasmapheresis in dogs reduces plasma protein concentration, without significantly altering plasma volume, glomerular filtration rate and plasma sodium concentration.The effects of acute hypoproteinemia on renal circulation is variable. In some cases, the renal plasma flow is not modified, while in others it is markedly decreased, leading to a rise in filtration fraction. The hemodynamic changes are observed in experiments inducing marked protein depletion.Acute hypoproteinemia increases sodium excretion exclusively in experiments where plasmapheresis has not reduced kidney irrigation.The lack of plasma volume expansion in the natriuretic animals cancels the necessity of postulating the secretion of some unknown natriuretic hormone to explain the decreased tubular reabsorption of sodium. The explanation of saline diuresis should be sought within the kidney itself, and the fall in peritubular oncotic pressure, occurring after plasmapheresis or during massive saline loading, offers an alternative explanation, which appears simpler and more rational.     

Impaired renal responsiveness to human atrial natriuretic peptide (hANP) in normotensive patients with type 1 diabetes mellitus

Summary Potential impairment of the efficacy of human atrial natiuretic peptide (human ANF-(99-126), hANP), the most potent endogenous natriuretic agent in healthy subjects, was examined in eight male normotensive patients with uncomplicated type 1 diabetes mellitus (aged 22–37 years). After giving informed consent, patients and eight male control subjects (aged 22–28 years) received in a random double-blind study design i.v. bolus injections of 100 µg hANP (Bissendorf peptide) or placebo. At base-line, patients differed from controls in elevated creatinine clearance (P<0.05) and in mild postprandial hyperglycemia. Whereas the responses of urinary cyclic guanosine monophosphate, the second messenger of hANP, were found to be normal in patients, the diuretic and natriuretic effects of hANP were grossly impaired when compared to controls (P<0.01); hANP resulted in increased plasma protein concentrations only in controls (P<0.05 vs patients). In both groups, creatinine clearance remained uninfluenced by hANP. There were similar decreases in plasma renin activity, aldosterone, levels, and blood pressure (systolic more than diastolic) in both groups (P<0.05 vs placebo). Heart rate and blood glucose remained unchanged. Thus, there is evidence for a decreased responsiveness to hANP exclusively of renal fluid, sodium, and chloride excretion in uncomplicated type 1 diabetes mellitus. The mechanisms responsible for this phenomenon remain obscure, neither a down regulation at the hANP receptor sites nor an hANP-induced shift from intra- to extravascular fluid volume are likely to be involved in its probably diabetes-specific pathogenesis.Abbreviations cGMP Cyclic guanosine monophosphate - hANP Human atrial natriuretic peptide - human ANF-(99-126) Human atrial natriuretic factor-(99-126)     

Increased brain natriuretic peptide and atrial natriuretic peptide plasma concentrations in dialysis-dependent chronic renal failure and in patients with elevated left ventricular filling pressure

Brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) plasma concentrations were measured in patients with dialysis-dependent chronic renal failure and in patients with coronary artery disease exhibiting normal or elevated left ventricular end-diastolic pressure (LVEDP) (n = 30 each). Blood samples were obtained from the arterial line of the arteriovenous shunt before, 2 h after the beginning of, and at the end of hemodialysis in patients with chronic renal failure. In patients with coronary artery disease arterial blood samples were collected during cardiac catheterization. BNP and ANP concentrations were determined by radioimmunoassay after Sep Pak C₁₈ extraction. BNP and ANP concentrations decreased significantly (P < 0.001) during hemodialysis (BNP: 192.1 ± 24.9, 178.6 ± 23.0, 167.2 ± 21.8 pg/ml; ANP: 240.2 ± 28.7, 166.7 ± 21.3, 133.0 ± 15.5 pg/ml). The decrease in BNP plasma concentrations, however, was less marked than that in ANP plasma levels (BNP 13.5 ± 1.8%, ANP 40.2 ± 3.5%; P < 0.001). Plasma BNP and ANP concentrations were 10.7 ± 1.0 and 60.3 ± 4. 0 pg/ml in patients with normal LVEDP and 31.7 ± 3.6 and 118.3 ± 9.4 pg/ml in patients with elevated LVEDP. These data demonstrate that BNP and ANP levels are strongly elevated in patients with dialysis-dependent chronic renal failure compared to patients with normal LVEDP (BNP 15.6-fold, ANP 2.2-fold, after hemodialysis; P < 0.001 or elevated LVEDP (BNP 6.1-fold, ANP 2.0-fold, before hemodialysis; P < 0.001), and that the elevation in BNP concentrations was more pronounced than that in ANP plasma concentrations. The present results provide support that other factors than volume overload, for example, decreased renal clearance, are also involved in the elevationin BNP and ANP plasma levels in chronic renal failure. The stronger elevation in BNP concentrations in patients with chronic renal failure and in patients with elevated LVEDP and the less pronounced decrease during hemodialysis suggest a different regulation of BNP and ANP plasma concentrations.[/ p]Abbreviations ANP atrial natriuretic peptide - BNP brain natriuretic peptide - LVEDP left ventricular end-diastolic pressure Correspondence to: C. Haug     

Fluid balance in patients with chronic renal failure assessed with N-terminal proatrial natriuretic peptide, atrial natriuretic peptide and ultrasonography

The N-terminal proatrial natriuretic peptide (proANP) has become an important parameter for assessing the prognosis of patients with cardiac disease. Its use for evaluating the hydration status in patients with chronic renal failure, however, is still under investigation. The present study comprised 12 haemodialysis (HD) and 17 pre-dialysis patients. In the HD patients, the inferior vena cava diameter during quiet expiration (IVCe) was estimated by ultrasonography and plasma concentrations of N-terminal proANP, atrial natriuretic peptide (ANP) and cyclic guanosine monophosphate (cGMP) were measured before and 4 h after termination of HD. In the pre-dialysis patients venous blood samples were taken during rest to measure plasma N-terminal proANP and ANP and serum creatinine. Normal values for N-terminal proANP and ANP were obtained from 18 healthy volunteers. The plasma concentrations of N-terminal proANP and ANP in healthy volunteers were 328 +/- 92 and 11.4.0 +/- 3.1 pM L-1, respectively. In pre-dialysis patients, serum creatinine ranged from 110 to 447 microM L-1 and was significantly correlated to plasma N-terminal proANP (r = 0.60, P < 0.05) but not to ANP. This may indicate that N-terminal proANP is more dependent on renal function for its clearance than ANP, which is probably cleared by extrarenal mechanisms as well. In HD patients, IVCe was significantly correlated to the three hormones before HD, most strongly to N-terminal proANP. After dialysis, IVCe was significantly correlated to ANP and cGMP but was not correlated to N-terminal proANP. This may suggest that proANP takes a longer time than other hormones to reflect changes in intravascular volume. In conclusion, N-terminal proANP is a hormone closely related to degree of renal function. Furthermore, it is a sensitive marker reflecting the interdialytic hydration status in HD patients, as indicated by its high correlation to IVCe, a standard method which is used frequently nowadays to assess the body hydration. However N-terminal proANP could not reflect the acute changes in fluid volume induced by HD, probably because it is slowly metabolized.     

限钠或补钠对充血性心衰大鼠心钠素及心功能的影响

目的：观察限钠或补钠对充血性心衰大鼠心钠素及心功能的影响。方法：将充血性心衰大鼠随机分为3组（心衰组、心衰限钠组、心衰补钠组J）,假手术大鼠为对照组,用放射免疫分析法测定各组血浆和心肌心钠素水平,同时检测心功能。结果：心衰限钠组血钠、心房心钠素及左室收缩压和动脉压显著低于心衰组,血浆和心室心钠素、右房压均显著高于心衰组;心衰补钠组血钠和动脉压与对照组无显著差别,血浆和心肌心钠素、右房压与心衰组无显著差别,左室收缩压显著高于心衰组,左室舒张末压显著低于心衰组。结论：心衰后适量补钠维持血钠平衡有利于心钠素发挥排钠利尿作用,改善心功能。     

Effects of chronic alpha and beta adrenoceptor blockade with labetalol on plasma catecholamines and renal function in hypertension

Summary Plasma catecholamines and renal function were evaluated in 18 patients with essential hypertension treated with the alpha and beta adrenoceptor blocking agent, labetalol. Following 6 weeks of labetalol therapy, blood levels of epinephrine and norepinephrine remained unaltered. Glomerular filtration rate and renal plasma flow were decreased similarly by about 20% (P<0.025). Tubular rejection fraction of sodium was increased by 36% (P<0.001) while sodium excretion was comparable to control conditions. Labetalol's potential to cause a mild reduction in kidney function should be considered, but may have no clinical consequences in most hypertensive patients receiving such treatment. The lack of increased plasma catecholamine levels during therapy supports the concept that labetalol's alpha-blocking potential is limited to post-junctional receptors, leaving the prejunctional feedback control of catecholamine release intact. Moreover, labetalol's blood pressure-lowering mechanism may be largely independent of changes in sympathetic nervous activity.     

Effects of brain natriuretic peptide on hemodynamics and renal function in dogs

A new natriuretic peptide has been found in the porcine brain and termed brain natriuretic peptide (BNP). To examine the effects of BNP on the cardiovascular system and kidney as compared with alpha-hANP (ANP), BNP, and ANP (33, 167, 667 pmol/kg) were intravenously administered to anesthetized dogs. BNP dose-dependently decreased arterial pressure and left atrial pressure and dose-dependently increased heart rate, cardiac output, renal blood flow, urine volume, and sodium excretion. These effects were not significantly different from the effects of respective doses of ANP. To eliminate the possibility that these results were confounded by opposing actions of the baroreflex system, we performed additional experiments following sinoaortic denervation and vagotomy. These results also demonstrated no differences between the effects of BNP and ANP on the measured variables. Finally, we determined that the pharmacokinetics of exogenously injected BNP and ANP are indistinguishable. These findings lead to the possibility that BNP physiologically works in the body in the same manner as ANP.     

Effects of indomethacin on renal hemodynamics and on water and sodium excretion by the isolated dog kidney

Summary Blood-perfused isolated dog kidneys demonstrate steady increases in blood flow and in water and sodium excretion which could be attributed to the accumulation of renal prostaglandins in the perfusing blood. This hypothesis was tested by adding indomethacin, a potent inhibitor of prostaglandins synthesis, to the perfusing blood.Indomethacin completely prevented the vasodilation observed in control kidneys, without affecting glomerular filtration rate. Urine volume was not modified but sodium excretion was enhanced while the steady free water clearance increment observed in the control kidneys was depressed by indomethacin. The sum of sodium and free water clearances which, in the absence of antidiuretic hormone, constitutes an index of the part of the filtered load of solutes which escapes proximal tubular reabsorption, was not modified by indomethacin. Finally, indomethacin partially maintained the osmotic cortico-papillary gradient which was abolished after 2 hrs perfusion in control kidneys.These data suggest that prostaglandins accumulation in the blood is probably the major cause of the vasodilation taking place in isolated blood-perfused kidneys. This vasodilation does not account for decreased proximal reabsorption but partially explains the ADH-resistant diabetes insipidus developing in the isolated kidney. Moreover, indomethacin inhibits sodium reabsorption in the ascending limb of Henle's loop and increases water transport in the collecting duct.     

硫氢化钠对慢性心力衰竭大鼠心脏功能和肾素-血管紧张素-醛固酮系统活性的影响

目的:探讨硫氢化钠(Na HS)对慢性心力衰竭(chronic heart failure,CHF)大鼠心脏功能和肾素(renin)-血管紧张素(Ang)-醛固酮(ALD)系统(RAAS)活性的影响。方法:本研究通过腹主动脉缩窄术构建CHF大鼠模型,将SD大鼠随机分为假手术组、模型组、Na HS低剂量组和Na HS高剂量组,每组6只。采用超声心动图检测每组大鼠治疗前及治疗结束后的左心室舒张末内径(LVEDD)、左心室收缩末内径(LVESD)和左心室射血分数(LVEF)。治疗结束后,采用ELISA试剂盒检测各组大鼠血浆中renin、AngⅡ和ALD的浓度。采用q PCR和Western blot实验分别检测各组大鼠心肌组织中血管紧张素转换酶(ACE)和血管紧张素Ⅱ1型受体(AT1R)的mRNA和蛋白表达。结果:经Na HS治疗后,与模型组和治疗前相比,Na HS低剂量组和Na HS高剂量组的LVEDD和LVESD均明显降低,而LVEF明显升高(P0.05);与Na HS低剂量组相比,Na HS高剂量组的LVEDD和LVESD降低,而LVEF升高(P0.05)。与假手术组相比,模型组大鼠血浆中renin、AngⅡ和ALD浓度显著升高(P0.05),心肌组织中ACE和AT1R的mRNA和蛋白表达显著上调(P0.05);与模型组相比,Na HS低剂量组和Na HS高剂量组大鼠血浆renin、AngⅡ和ALD浓度显著降低(P0.05),心肌组织中ACE和AT1R的mRNA和蛋白表达显著下调(P0.05);Na HS高剂量组大鼠血浆renin、AngⅡ和ALD浓度及心肌组织中ACE和AT1R的mRNA和蛋白表达显著低于Na HS低剂量组(P0.05)。结论:Na HS可通过抑制RAAS的活性改善CHF大鼠的心功能,且高剂量组的改善效果优于低剂量组。     

The effect of anesthesia on hemodynamics and renal function in the rat

Although many renal physiologic studies in the rat have utilized pentobarbital anesthetized animals, there has been no systematic evaluation of the effects of barbiturate anesthesia on renal function. We therefore compared systemic hemodynamic and renal function parameters in conscious (C) and pentobarbital anesthetized (A) rats. Cardiac index and renal blood flow as assessed by microspheres were greater in C rats while systemic and renal vascular resistance were less in C rats. Although basal glomerular filtration rate was similar in both groups of animals, glomerular filtration rate following hypotonic volume expansion was greater in C than A rats. During hypotonic volume expansion, distal delivery as estimated by the sum of free water and sodium clearances was greater in C rats. In contrast, function of the distal nephron as assessed by maximum fractional free water clearance during hypotonic volume expansion and by solute free water reabsorption at maximum levels of osmolar clearance were comparable in C and A rats. Collecting duct water permeability as assessed by the response to exogenous vasopressin was similar in C and A rats. Following an exogenous sodium chloride load, C rats excreted 16% more of the sodium. No differences in measured whole blood or plasma volume were present when C and A rats were compared.We conclude that pentobarbital does not impair basal glomerular filtration rate, distal nephron function or the water permeability response of the collecting duct. Pentobarbital does result in alterations in systemic and renal hemodynamics which may contribute to the failure of A rats to normally excrete a saline load.     

Digoxin-quinidine interaction in patients with renal failure

Summary Investigations were performed in order to study whether or not quinidine would exert similar effects on the serum digoxin concentration in patients with renal failure as in normal subjects. Fourteen out of fifteen patients showed a significant increase of the serum digoxin level after four days of quindine application. This indicates, that the quinidine effect is not solely caused by a decrease of the renal digoxin clearance, although nine patients, not being hemodialysed, revealed a correlation between their creatinine clearance and the rise of the serum digoxin concentration after quinidine. As however, the patients on hemodialysis did not show higher digoxin levels than those treated conservatively, it is suggested that the degree of the uremic intoxication might be responsible for the observed correlation.     

心房钠尿肽在产科领域的研究进展

心房钠尿肽是一种具有强大的利钠、利尿、扩张血管作用的肽类激素,在胎盘和胎膜组织有丰富的表达,对维持妊娠期间正常的子宫胎盘循环和胎儿生长发育中起重要作用。目前研究发现,心房钠尿肽与妊娠期高血压疾病、胎儿生长受限、胎儿宫内窘迫等一些产科疾病关系密切。心房钠尿肽浓度变化对于这些疾病的诊断、治疗、及预后判断均起一定的作用。不久的将来,心房钠尿肽作为一种药物在临床的应用将越来越广。     

Binding sites of atrial natriuretic peptide in human renal tissue — Quantification by in vitro receptor autoradiography

Summary Specific binding sites for atrial natriuretic peptide (99–126) in different areas of normal human renal tissue were quantified by in vitro autoradiography. Our data represent the first characterization of ANP binding sites in different structures of the human kidney. Characterization of ANP binding revealed by Scatchard plot analysis a single class of high affinity binding sites in the glomeruli (K _d 0.53±0.11 nM;B _Max 74.4±17.86 fmol/mg protein), the vasculature (K _d 0.18±0.014 nM;B _Max 91.6±25.02 fmol/mg protein), and the medulla (K _d 0.34±0.13 nM;B _Max 106.0±30.61 fmol/mg protein). These sites may play a key role in the actions of the cardiac hormone in human kidney and in the ameliorating effects of ANP in the recovery from acute renal failure.Abbreviations ANP Atrial natriuretic peptide - cGMP Cyclic guanosine monophosphate     

慢性心力衰竭合并慢性肾炎患者尿液中B型尿钠肽水平与心功能的相关性研究

目的：探讨慢性心力衰竭(chronic heart failure,CHF)合并慢性肾炎患者尿液中血清B型钠尿肽(B-natriuretic peptide,BNP)水平与心功能的相关性。方法：选取2013年6月至2015年6月在我院接受治疗的慢性心力衰竭患者为观察对象,根据其是否合并慢性肾炎分为CHF组和CHF合并慢性肾炎组。观察两组患者肾功能指标及尿BNP水平,比较两组患者心功能指标的差异,分析肾功能指标、尿BNP与心功能的相关性。结果：CHF合并慢性肾炎组患者尿素氮(blood urea nitrogen, BUN)、血清肌酐(serum creatinine,SCr)和BNP水平明显高于CHF组,而肾小球滤过率(glomerular filtration rate,GFR)水平明显低于CHF组,差异具有统计学意义(P<0.05);CHF合并慢性肾炎组患者左心房直径(left atrial diameter,LAD)、右心房直径(right atrial diameter,RAD)、左室收缩末内径((left ventricular end systolic diameter,LVESD)和左室舒张末内径(left ventricular end diastolic diameter,LVEDD)水平明显高于CHF组患者,左室射血分数(left ventricular ejection fractions, LVEF)水平明显低于CHF组,差异具有统计学意义(P<0.05);CHF合并慢性肾炎患者的BUN、SCr、BNP与LAD、RAD、LVESD和LVEDD正相关,与LVEF负相关,GER水平与LAD、RAD、LVESD和LVEDD负相关,与LVEF正相关。结论：慢性心力衰竭合并慢性肾炎患者尿液BNP水平较高,且与患者的心功能指标密切相关,可作为临床监测指标。     

Atrial natriuretic peptide and atrial pressure in patients with congestive heart failure

To define the relation between atrial pressures and the release of atrial natriuretic peptide, we measured plasma concentrations of the peptide in 26 patients with cardiac disease--11 with normal atrial pressures and 15 with elevated atrial pressures (11 of these 15 had elevated pressures in both atria). Mean peptide levels (+/- SEM) in the peripheral venous blood were increased in the 11 patients with cardiac disease and normal atrial pressures, as compared with 60 healthy controls (48 +/- 14 vs. 17 +/- 2 pmol per liter). In the patients with elevated atrial pressures, peptide concentrations were increased twofold in peripheral venous, right atrial, pulmonary arterial, and systemic arterial plasma, as compared with the concentrations in the patients with normal atrial pressures. A step-up in peptide concentration was seen between the venous and right atrial plasma (P less than 0.002) and between the pulmonary and systemic arterial plasma (P less than 0.01), suggesting release of the peptide from the atria. A linear relation was found between right atrial pressure and right atrial peptide concentration (r = 0.835, P less than 0.001) and between pulmonary wedge pressure and the systemic arterial peptide concentration (r = 0.866, P less than 0.001). Right atrial pressure and the peptide concentration both increased with exercise testing in the nine patients evaluated. We conclude that the release of atrial natriuretic peptide is at least partly regulated by right and left atrial pressures. Distinguishing the relative contributions of the two atria and defining the role of peptide release in the pathogenesis of heart failure will require further investigation.     

Effects of nifedipine on renal responses to human atrial natriuretic peptide in healthy subjects and normoglycemic patients with type 1 diabetes mellitus

Summary We examined renal responses to a pharmacological dosage of human atrial natriuretic peptide (hANP) and the potential interference of nifedipine administration with the effects of hANP on kidney function in healthy subjects and normoglycemic patients with type 1 diabetes mellitus. Ten healthy volunteers (age, 28±1 years) and ten patients (age, 33±2 years; diabetes duration; 14±3 years; HbAI 7.2%±0.2%) were studied. According to a double-blind, randomized, placebo-controlled trial design, three experiments were performed in each subject using the doubledummy technique: placebo only, hANP only, and nifedipine+hANP. As i.v. bolus injection 100 µg hANP was given; nifedipine was applied buccally, at a dose of 10 mg 90 min before and at a dose of 5 mg together with hANP injection. At base-line and in the placebo only experiment, patients did not differ from controls. In the hANP only experiment, in both groups hANP resulted in increased urinary volume and both sodium and chloride excretion (P<0.05 vs placebo only experiment). In patients, hANP-induced increase in electrolyte excretion was greater than in controls (P<0.05). In the nifedipine + hANP experiment, hANP-induced changes in renal indexes were enhanced in controls (P<0.05 vs hANP only experiment) but not in patients. Thus, diuretic response to nifedipine + hANP in patients was decreased in comparison with controls (P<0.05). In patients, however, nifedipine administration decreased the hANP-induced increase in urinary albumin excretion (P<0.05 vs hANP only experiment). Creatinine clearance was uninfluenced throughout the experiments.There were similar decreases in blood pressure in patients and controls after nifedipine administration (P<0.05 vs placebo only experiment). The increase in heart rate after nifedipine was more pronounced in patients than in controls (P<0.05). Conversely, plasma renin activity was stimulated by nifedipine only in controls (P<0.05 vs placebo only experiment). In this study hANP had no effect on heart rate, blood pressure, or plasma renin activity. There was a short-term increase in hANP levels in plasma after nifedipine administration in controls (P<0.05 vs placebo only experiment) but not in patients. In contrast to a previous study, where renal responses to the same pharmacological dosage of hANP were decreased in patients with type 1 diabetes mellitus with HbAI exceeding the normal range, there is no impairment of renal responsiveness to an i.v. bolus of hANP in patients with HbAI within the normal range. Nifedipine and hANP have synergistic effects on kidney function in healthy subjects. It remains to be studied, however, by which mechanism(s) this synergism could be obscured in diabetes patients. Moreover, the increase in hANP levels after nifedipine administration exclusively in controls merits further investigation.Abbreviations hANP Human atrial natriuretic peptide - HbAI Glycosylated hemoglobin AI - HbAI c Glycosylated haemoglobin AI c     

Effects of calcium supplementation and deoxycorticosterone on plasma atrial natriuretic peptide and electrolyte excretion in spontaneously hypertensive rats

The effects of calcium and the mineralocorticoid deoxycorticosterone (DOC) on blood pressure were studied in four groups of spontaneously hypertensive rats (SHR): (1) control; (2) calcium; (3) deoxycorticosterone and; (4) deoxycorticosterone + calcium. Calcium was given as 1.5% calcium chloride in drinking fluid and deoxycorticosterone by weekly subcutaneous injections (25 mg kg^-1). During the nine weeks of treatment the increase in systolic blood pressure was enhanced in the deoxycorticosterone and attenuated in the calcium group, whereas the deoxycorticosterone + calcium group did not deviate from control. Total plasma calcium was elevated in the calcium group. Plasma concentrations of sodium and atrial natriuretic peptide (ANP) were increased by deoxycorticosterone while neither of the calcium-treated groups differed from control in these respects. Urinary excretions of calcium and sodium were increased in both groups receiving calcium, and also the deoxycorticosterone group excreted more calcium into urine than the control. Adrenergic nerve density in a section of the mesenteric artery and the urinary excretion of noradrenaline and adrenaline were similar in all study groups. The results indicate that calcium supplementation can attenuate the development of hypertension and prevent the deoxycorticosterone-induced blood pressure rise in SHR, possibly by influencing sodium metabolism as seen in increased natriuresis, and by preventing the actions of deoxycorticosterone on sodium balance.     

奥美沙坦酯对慢性心力衰竭小鼠肾脏损伤的保护作用

目的: 探讨奥美沙坦酯对慢性心力衰竭小鼠肾脏损伤的影响。方法: 健康C57小鼠分为假手术组(sham组)、慢性心力衰竭组(CHF组)和奥美沙坦酯治疗组(OLM+CHF组)。以冠状动脉左前降支结扎法建立慢性心力衰竭小鼠模型,其中奥美沙坦酯治疗组以10 mg/kg剂量每天胃饲。12周时观察各组小鼠心率、血压、心功能状况、血肌酐、血尿素氮、血浆和肾脏血管紧张素Ⅱ水平;real-time PCR法检测肾脏肾素、血管紧张素1型受体(AT1R)和血管紧张素原(AGT)的表达情况,PAS染色观察肾组织结构变化。结果: 与shan组相比,CHF组和OLM+CHF组左室舒张末期内径(LVDd)和左室收缩末期内径(LVDs)显著增加(P＜0.05),短轴缩短率(FS)和射血分数(EF)显著降低(P＜0.05)。与sham组相比,CHF组收缩压、血肌酐和血尿素氮含量显著增高,OLM+CHF组以上指标较CHF组均显著降低(P＜0.05)。与sham组相比,CHF组血浆和肾脏血管紧张素Ⅱ水平增高,肾素、AT1R和AGT表达增高(P＜0.05),OLM+CHF组肾脏血管紧张素Ⅱ水平、肾素、AT1R和AGT表达较CHF组均显著降低(P＜0.05)。CHF组PAS染色可见肾小球系膜区扩张,肾小管间质PAS阳性染色物明显增多。OLM+CHF组肾小球系膜区和肾小管间质PAS染色阳性物质与CHF组相比明显减少。结论: 慢性心力衰竭可使肾内肾素血管紧张素系统激活并导致肾脏损伤,奥美沙坦酯通过抑制血管紧张素Ⅱ起到肾脏保护作用。