Increased transcapillary escape rate of albumin and IgG in essential hypertension

Transcapillary escape rates of albumin and IgG (fractions of intravascular mass of albumin and IgG that pass to the extravascular space per unit time) were determined simultaneously from the initial disappearance of intravenously injected 131I human albumin and 125I human IgG in seven untreated subjects suffering from essential hypertension. The average mean arterial blood pressure of these subjects 193/119 mmHg; four subjects had grade I-III funduscopic changes. Transcapillary escape rates of albumin (TERalb) and IgG (TERIgG) were found significantly increased in the hypertensive subjects, average 7.8 +/- 0.9 (SD) and 4.7 +/- 1.0 (SD) %/h, respectively, compared with normal values of mean 5.2 +/- 1.0 (SD) and 3.0 +/- 0.7 (SD) %/h, respectively (P less than 0.01). There was a statistically significant positive correlation between the mean arterial blood pressure and TER of albumin and of IgG (P less than 0.001). The TERIgG/TERalb ratio was about the same in the hypertensives and the normals. Confirming a previous observation, we found an increase in the daily urinary albumin excretion rate from a normal average of 9.1 (range, 2.4-20.4)mg/24 h to 96 (range, 5.6-565) mg/24 h, P less than 0.05. The present findings can best be explained by increased filtration through normal pores between the endothelial cells in the microvasculature, due to the high arterial blood pressure.     

Long-term smoking increases transcapillary escape rate of albumin.

Transcapillary escape rate of albumin was measured in 11 young and 10 healthy, elderly male subjects. Approximately half of the subjects were chronic cigarette smokers. Transcapillary escape rate of albumin expressed as percentage of decrease in specific activity of plasma albumin per hour averaged 12.3% in long-term smokers. This value was significantly elevated and twice as high as values measured in young smokers and in young and elderly non-smokers. It is concluded that capillary permeability to albumin is increased in long-term smokers. Further studies are warranted to examine the pathophysiological mechanism and to what extent this abnormality is reversible.     

Increased transcapillary escape rate of albumin in patients with cirrhosis of the liver

The transcapillary escape rate of albumin (TERalb), i.e. the fraction of intravascular mass of albumin that passes to the extravascular space per unit time, was determined from the disappearance of intravenously injected 125I-labelled human serum albumin during the first 60 min after injection in nine patients with cirrhosis of the liver. Six of the patients had ascites. The wedged hepatic venous pressure or splenic pulp pressure ranged from 20 to 30 mmHg, mean 26 mmHg. Plasma albumin concentration was low, but plasma volume was slightly enlarged, and thus the intravascular mass of albumin was only moderately reduced. The transcapillary escape rate of albumin was significantly elevated in all the cirrhotics, mean 10.2%/h, range 8.8 to 12.3%/h, in comparison to values for twenty-eight normal subjects 5.4%/h, range 3.5-7.2%/h. Our results can best be explained by increased filtration out of the vessels in the portal system, due to the increased portal venous pressure. The increased TERalb probably contributes to the formation of oedema and ascitic fluid.     

Increased transcapillary escape rate of albumin in elderly subjects due to long-term smoking habits

Summary. Transcapillary escape rate of albumin (TER) expressed as percentage decrease in specific activity of plasma albumin per hour was measured in 44 healthy male subjects, 10 young non-smokers (median age 24.0 years, range 21–33), 10 young smokers (30.5 years, range 27–36), 10 elderly non-smokers (64.0 years, range 51–75) and 14 elderly smokers (61.5 years, range 54–69). In addition urinary albumin excretion rates were measured in 15 of the elderly subjects. The subjects were investigated after overnight fasting and abstention from tobacco. Median TER was 7.33% (interquartile range 5.82–9.90) in the elderly smoking subjects. This value was significantly elevated as compared to elderly non-smokers, 4.47% (2.93–5.83), young non-smokers, 3.70% (2.24–6.30) and young smokers, 4.25% (2.80–4.44). A statistically non-significant (P=0.064) tendency of a higher urinary albumin excretion rate was observed in elderly smokers. This agrees with other investigations showing slightly increased albuminuria in smokers compared with non-smokers. The differences were not related to differences in blood pressure, plasma cholesterol, weight, or abuse of alcohol in the elderly subjects. Diabetic subjects with an increased TER to levels comparable with levels in long-term smokers have increased urinary albumin excretion rates, which seems to be greater than in long-term smoking subjects. It is suggested that increased TER in long-term smokers may indicate a vascular dysfunction affecting either capillary permeability or endothelial surface area.     

Changes in plasma volume, in transcapillary escape rate of albumin and in subcutaneous blood flow during hypoglycaemia in man

Hypoglycaemia was induced by insulin injected intravenously (0.15 i.u./kg body weight) in seven healthy young males. Plasma volume was measured before and during hypoglycaemia by intravenous injection of 125I before hypoglycaemia and of 131I during hypoglycaemia. Plasma volume decreased and transcapillary escape rate increased significantly during hypoglycaemia. Skin temperature and local subcutaneous adipose tissue blood flow were measured in four different regions. Both tended to decrease during hypoglycaemia and decreased significantly 2 h after hypoglycaemia. There was no correlation between changes in the two measurements, suggesting that there is no simple relationship between subcutaneous blood flow and skin temperature during hypoglycaemia.     

Lack of effect of fish oil supplementation on coagulation and transcapillary escape rate of albumin in insulin-dependent diabetic patients with diabetic nephropathy

OBJECTIVE: We studied the effect of a diet supplementation with fish oil in insulin-dependent diabetic patients with nephropathy in order to evaluate whether abnormal transcapillary escape rate of albumin and procoagulant activity in these patients could be modified. METHODS: A double-blind, randomized, controlled study was carried out at a tertiary referral centre. The subjects were 29 insulin-dependent diabetic patients with nephropathy. One year of fish oil supplementation (4.6 g n-3 fatty acids/day) was compared with placebo (olive oil). The main outcome measures were N-3 fatty acid proportions of platelet lipids, transcapillary escape rate of albumin, prothrombin fragment 1 + 2, thrombin-antithrombin complexes, markers of fibrinolysis, fibrinogen, factor VII antigen and activity, thrombomodulin, von Willebrand factor, platelet factor 4 and beta-thromboglobulin. These were measured every 6 months. RESULTS: Neither transcapillary escape rate of albumin (7.4 (median) (5.0-9.8) (range) % vs. 7.0 (4.6-10.6) %) nor prothrombin fragment 1 + 2 (0.97 (0.72-2.40) nmol/L vs. 1.01 (0.59-3.11) nmol/L) changed after 12 months of fish oil supplementation. CONCLUSION: Increased transcapillary escape rate of albumin and activity could not be modified during diet supplementation with fish oil in insulin-dependent diabetic patients with nephropathy.     

Interstitial albumin mass and transcapillary extravasation rate of albumin in DMBA-induced rat mammary tumours

Transcapillary extravasation rate for radio-iodinated human serum albumin (I-HSA) from plasma to interstitial fluid, interstitial albumin mass and interstitial albumin concentration have been determined in dimethyl-benz-alpha-anthracene (DMBA)-induced mammary tumours in rats. The plasma radioactivity of tracer was kept constant in awake, freely moving rats by a continuous infusion of I-HSA from 1 to 72 h after an initial priming dose. Capillary leakiness for I-HSA was calculated as the plasma equivalent volume of I-HSA located extravascularly after 1 h infusion divided by the blood volume in the tissue, i.e. as the fractional extravasation rate (FER). The experiments showed that FER was highest in tumours while intestine and skin had FER of about 70% and 25% that of tumour respectively. Heart and skeletal muscle had similar FER about 1/8 that of tumour. Interstitial albumin concentration in tumour averaged 42% of plasma albumin concentration in tumour. Intestine, heart and skeletal muscle had interstitial albumin concentrations between 34 and 37% of plasma albumin concentration while skin had an albumin concentration averaging 20% that of plasma. Lymph flow was calculated as the product of the fractional turnover rate constant for interstitial albumin and interstitial volume (extravascular 51Cr-EDTA volume) and averaged 36.7 X 10(-3) mg/g X h in tumour while intestine and heart had lymph flows of 19.1 X 10(-3) and 14.1 X 10(-3) ml/g X h respectively. In muscle and skin lymph flow was 2.4 X 10(-3) and 18.3 X 10(-3) ml/g X h respectively. It is suggested that the high interstitial fluid pressure previously observed in these tumours will contribute in maintaining interstitial volume in a steady state by opposing fluid filtration into the interstitium and maintaining a lymph flow high enough to remove excess fluid and protein from the interstitium.     

Transcapillary insulin transfer in human skeletal muscle

BACKGROUND: Transcapillary insulin transfer is considered a rate-limiting step in insulin action at supraphysiological insulin concentrations. However, it remains unclear whether this concept also applies for physiological conditions. MATERIALS AND METHODS: In the present study we set out to characterize transcapillary insulin transfer by measuring insulin concentrations in plasma and interstitial space fluid of skeletal muscle during an oral glucose tolerance test and euglycaemic hyperinsulinaemic clamp conditions, respectively. For this purpose we employed in vivo microdialysis of skeletal muscle in conjunction with an ultrasensitive insulin assay in eight healthy lean male volunteers (aged 25 +/- 1 years). RESULTS: Insulin concentrations at baseline were 48 +/- 8 pmol x L(-1) in plasma and 19 +/- 4 pmol x L(-1) in the interstitium (P = 0.002). The mean interstitium to plasma ratio at baseline was 0.48 +/- 0.09 pmol x L(-1). During the oral glucose tolerance test the interstitium to plasma ratio remained unchanged (0.43 +/- 0.12, P = NS vs. baseline), but was significantly reduced during euglycaemic hyperinsulinaemic clamp conditions at steady-state hyperinsulinaemia (0.12 +/- 0.01, P = 0.01 vs. baseline). CONCLUSION: In summary there is a substantial transcapillary insulin gradient in healthy human skeletal muscle under baseline and glucose-stimulated conditions. Our findings support the hypothesis of a saturable transcapillary insulin transport representing a partly rate-limiting step for insulin action.     

Plasma-to-ascitic fluid transport rate of albumin in patients with decompensated cirrhosis. Relation to intraperitoneal albumin

Summary. Albumin-kinetics and haemodynamic studies were performed in 20 patients with decompensated liver cirrhosis in order to improve the knowledge on genesis and perpetuation of hepatic ascites, especially with respect to determinants of intraperitoneal protein. A positive relationship was found between the plasma-to-peritoneal transport rate of albumin (index of ‘lymph-imbalance’) and the mass of intraperitoneal albumin (r_log= 0·82, P< 0·001), indicating a significant role of ‘lymph-imbalance’ to sequestration of protein in the peritoneal cavity. Ascitic fluid albumin concentration was on the average 0.22 of that of plasma and directly correlated to the plasma concentration (r_lin= 0·68, P < 0·01). The hydrostatic pressure difference across the splanchnic microvasculature (assessed as wedged hepatic vein minus inferior vena caval pressure) was directly correlated to the effective (plasma minus ascitic fluid) oncotic pressure (r_lin= 0·74, P< 0·001) but significantly higher than that (P<0·005), indicating a ‘non-equilibrium’ in the splanchnic Starling forces. The results point to a multivariate genesis and perpetuation of cirrhotic ascites as laid down in the ‘lymph-imbalance’ theory of ascites formation, whereas a ‘fluid equilibrium’ theory seems to be too simple, especially with respect to explain protein sequestration in the peritoneal cavity.     

Irbesartan reduces the albumin excretion rate in microalbuminuric type 2 diabetic patients independently of hypertension: a randomized double-blind placebo-controlled crossover study

OBJECTIVE: ACE inhibitors delay the progression from incipient to overt diabetic nephropathy and reduce albumin excretion rate (AER), independently of blood pressure. Angiotensin II type 1 receptor antagonists produce similar effects on microalbuminuria and mean arterial pressure. The aim of this study was to evaluate the effect of irbesartan on microalbuminuria and blood pressure in hypertensive and normotensive type 2 diabetic patients. RESEARCH DESIGN AND METHODS: Sixty-four microalbuminuric hypertensive (group 1) and 60 microalbuminuric normotensive (group 2) type 2 diabetic male patients, matched for age, BMI, HbA(1c), and diabetes duration, were enrolled. Each group was divided into two subgroups receiving either irbesartan (150 mg b.i.d. orally) or placebo for 60 days. After 15 days of washout, irbesartan was given to the subgroups who had received the placebo, and vice versa, in a randomized double-blind crossover study. RESULTS: In microalbuminuric hypertensive type 2 diabetic subjects, irbesartan reduced 24-h mean systolic and diastolic pressure and AER. In microalbuminuric normotensive type 2 diabetic patients, irbesartan reduced AER. CONCLUSIONS: These results indicate the beneficial effects of irbesartan on AER in type 2 diabetic subjects, independently of its antihypertensive effects.     

尿系列蛋白测定在高血压诊治中的意义

目的：了解尿微量白蛋白（mAlb)、转铁蛋白（TF）、IgG在原发性高血压诊治中的意义。方法：对高血压患者与健康人的mAlb、TF、IgG以及经尿肌酐（Cr）标化后结果进行比较。再将高血压病人依舒张压分成“正常”血压组、轻度高血压组、中度高血压组、重度高血压组4亚组,4亚组与对照组及相互之间作比较。结果：高血压组的mAlb、TF、IgG、尿微量白蛋白／尿肌酐（mAlb/Cr)水平与对照组比较差别显著（P＜0．001,P＜0．001,P＝0．024,P＝0．006）,mAlb的阳性率随血压升高而升高;高血压4亚组与对照组相比,mAlb、TF、IgG、mAlb/Cr均有显著差异（P＜0．01）。“正常”血压组、轻度高血压组分别与重度高血压组的mAlb,IgG比较,有显著性差异（P＝0．019,P＝0．048,P＝0．036,P＝0．028）;中度高血压组与重度高血压组的mAlb比较有差异,但未达到统计学意义（P＝0．05）。mAlb、TF、IgG、mAlb/Cr与舒张压的相关性有显著性差异,TF／Cr、IgG/Cr则与平均压的相关性有显著性差异。结论：尿系列微量蛋白测定对高血压治疗过程中肾脏的细微变化的早期发现和确定治疗的目标,都有一定的临床意义。