Renin,aldosterone and Cortisol during ethanol intoxication and hangover

The effect of ethanol intoxication and hangover on plasma renin activity (PRA), plasma aldosterone (PA) and plasma Cortisol (PC) concentrations was studied in 7 healthy supine men in controlled clinical conditions during 18 h beginning at 6 p.m. Large individual variation was observed in the response of PRA, PA and PC to ethanol. Following ethanol, stimulation of PRA was observed at the 14th and the 16th hour (P<0.05), of PA at the 4th and the 6th hour (P<0.01 and P<0.05, respectively) and of PC at the 4th and the 14th hour (P<0.01 andP<0.05, respectively). Ethanol ingestion suppressed PC during the first hour (P<0.02). Water ingestion at 8 a.m. suppressed PA between the 14th and the 16th hour (8–10 a.m.) in control and ethanol experiment (P<0.01 and P<0.005, respectively). There was a dissociation between PRA and PA, but intra-individually PRA and PA correlated fairly or well. Plasma arginine vasopressin (AVP) and PC were also significantly correlated. The results suggest that changes in PA and PC as well as the dissociation of PRA and PA after ethanol ingestion might be partly related to dehydration and to the increased secretion of hypothalamic and pituitary hormones as well as to sodium and potassium balance. There was a biphasic effect of ethanol, including an initial suppression of PC and a subsequent increase of PC, PRA and PA. Upright posture appears to exaggerate the stimulating effect of ethanol on PRA, PA and PC.     

Effects of calcium on renin and aldosterone in the rat.

CaCl2 suppresses the plasma renin activity (PRA) response to Na+ deprivation in the rat. The purpose of the present study is:1) to determine if the effect of Ca2+ on PRA is modified by the anion delivered with Ca2+, and 2) to evaluate the effect of Ca2+ loading on aldosterone production. PRA and in vitro aldosterone production by adrenal quarters were measured after a 7-day balance study. On a low Na+ diet, PRA of animals drinking 1% CaCl2 (13.1 ng/ml per h +/- 1.3 SE), but not of animals drinking 1% calcium gluconate, was suppressed (P less than 0.05) compared to that of water-drinking controls (20.9 ng/ml per h +/- 2.1 SE). Aldosterone production of calcium gluconate and CaCl2-loaded animals was greater than that of controls (P less than 0.01). K+ balance of CaCl2 and calcium gluconate-drinking animals was more positive than that of controls (P less than 0.05). In conclusion, inhibition of PRA by CaCl2 but not by calcium gluconate indicates that the effect of Ca2+ on PRA is modified by the accompanying anion. Both CaCl2 and calcium gluconate stimulate aldosterone production, independent of changes in PRA, possibly due to an effect of Ca2+ on K+ balance.     

Blood pressure regulation, peripheral renin activity and aldosterone in patients with pyelonephritic renal scarring

Patients with renal scarring due to previous upper urinary tract infections (UTI) are at risk of developing hypertension and renal insufficiency. In this study glomerular filtration rate (GFR), systolic (SBP) and diastolic (DBP) blood pressure, peripheral renin activity (PRA), plasma (p-Aldo) and urine aldosterone (u-Aldo), the urinary excretion of sodium (UNa) and potassium (UK) and the fractional sodium (CNa/CIn) and potassium (CK/CIn) excretion were determined in 22 female patients with verified renal scarring and a history of febrile UTI and in nine age-matched healthy women with normal i.v. urograms. The patients had significantly lower GFR, higher SBP, higher PRA and higher CK/CIn than the healthy controls. A significant correlation between CNa/CIn and SBP (r = 0.51, P less than 0.05), DBP (r = 0.50, P less than 0.05) and PRA (r = -0.47, P less than 0.05) was found. The ratio of UK/UNa was significantly correlated to SBP (r = -0.43, P less than 0.05), DBP (r = -0.44, P less than 0.05), PRA (r = 0.65, P less than 0.01) and p-Aldo (r = 0.68, P less than 0.01). It is concluded that the renin-aldosterone system probably is involved in the pathogenesis of hypertension in patients with pyelonephritic renal scarring and that screening determinations of UNa and UK may prove useful for detection of individuals with increased PRA and p-Aldo.     

Effects of bile duct ligation and captopril on salt appetite and renin-aldosterone axis in rats.

A ligation of the common bile duct (BDL) produces cholestasis and hypotension and increases the daily ingestion of sodium chloride solutions in rats. Low-dose captopril (CAP) treatment also modifies the ingestion of water and sodium in naive rats, and may do so in cholestatic rats. This study examined whether the elevated ingestion of saline by Long-Evans rats after BDL is associated with increased plasma renin activity (PRA), and whether treatment with a low dose of the angiotensin converting-enzyme inhibitor CAP further exacerbates fluid intake and PRA after BDL. In these experiments water and 0.3 M saline intake and PRA and plasma aldosterone (PA) were measured in naive and CAP-treated BDL and sham-ligated rats. We found that BDL elevated rats' daily saline intake 2 weeks after the ligation procedure but had no effect on PRA. CAP (0.1 mg/mL) placed in the drinking water of some BDL rats further increased saline intake. Both PA and hematocrits tended to be reduced in BDL rats, whereas PRA was elevated in both BDL and sham-ligated rats receiving CAP in the drinking water or by gavage (0.1 mg/mL in 10 mL/kg). The data suggest that the ingestion of saline by rats can be modified by BDL and CAP administration, but that exaggerated saline intake in BDL rats is not associated with excessive renin secretion.     

Importance of chloride for acute inhibition of renin by sodium chloride.

To evaluate the contribution of chloride to acute renin inhibition by sodium chloride, plasma renin activity (PRA) was measured before and after peripheral venous infusion of NaCl, NaHCO3, NaBr, NaNO3, lysine monohydrochloride, or lysine glutamate in NaCl-deprived rats. In contrast to controls and animals infused with other sodium salts, PRA decreased (P less than 0.01) after infusion with NaCl [from 28.3 +/- 2.8 to 13.3 +/- 1.8 ng/ml per h (SE)] and NaBr (from 40.6 +/- 6.2 to 21.8 +/- 3.9 ng/ml per h), and renal tubular halide reabsorption increased (P less than 0.05). Arterial pressure, plasma volume, inulin clearance, net sodium balance, serum Na+ and K+, and pH were not different among sodium-loaded groups. PRA was also suppressed (P less than 0.01) by infusion with lysine monohydrochloride (from 51.6 +/- 5.4 to 32.4 +/- 5.1 ng/ml per h) but not with lysine glutamate. These results suggest that inhibition of renin by sodium is dependent on an intrarenal effect of chloride. During infusion with sodium salts which suppressed renin, negative free water clearance (TcH2O) increased, whereas infusion with sodium salts that did not inhibit renin resulted in either no change or decreased TcH2O. The association of renin inhibition and increased TcH2O indirectly supports the hypothesis that renin suppression by chloride is related to the magnitude of absorptive chloride transport in the thick ascending limb of the loop of Henle.     

Secretion of anterior pituitary hormones in man: effects of ethyl alcohol.

The possibility that previously described effects of ethyl alcohol on peripheral endocrine glands might be mediated via pituitary prompted this investigation on the effects of ethanol on anterior pituitary secretion. Nine healthy male subjects were given beverage containing ethanol (1.5 g/kg) or beverage alone per os in a randomized cross-over study and plasma ACTH, FSH, GH, LH and TSH were measured by specific radioimmunoassays up to 15 h and the urinary levels of adrenaline and noradrenaline by fluorometry. A combined LRF and TRF test was also carried out in similar series of experiments. During the whole experiment there were no significant differences in the plasma levels of ACTH, FSH and TSH or in the urinary levels of adrenaline and noradrenaline between ethanol treated and control subjects. Plasma FSH, LH and TSH responses to LRF and TRF stimulation were also similar in alcohol treated and control subjects. Plasma ACTH values were high (113-270 pg/ml) both in control and ethanol experiment suggesting that the subjects experienced apprehension toward the experiment. Plasma GH level exhibited a non-sleep related burst in the late evening (from 0.4 ng/ml at 6 p.m. to 3.1 ng/ml at 10 p.m., p less than 0.01). This increase was not seen after alcohol ingestion (p less than 0.01). Plasma LH levels were significantly lower after 6 and 13 h in alcohol treated subjects than in controls (65 vs. 106 ng/ml, p less than 0.01 and 74 vs. 121 ng/ml, p less than 0.05 respectively). Because ethanol had no effect on the resting level of plasma GH or on the LH response to LRF, WE SUggest that ethanol exerts these effects on a suprapituitary site.     

Renin-angiotensin-aldosterone system in experimental renal hypertension in the rabbit.

Hypertension was produced in 25 rabbits by constricting the right renal artery and leaving the opposite kidney intact (two-kidney hypertension). After 30 days mean arterial pressure and plasma renin activity (PRA) were significantly elevated (P less than 0.01), and arterial pressure was correlated with PRA (r = 0.551, P less than 0.01); however, not all hypertensive rabbits had elevated PRA, and in animals in which sodium balance was monitored, only rabbits in negative sodium balance had increased levels of PRA. To investigate the role of angiotensin II (A-II) in the hypertension, [1-sarcosine,8-alanine]angiotensin II was infused at 6 mug/kg per min for 30 min in anesthetized hypertensive animals (n = 25). For the group, arterial pressure fell significantly (P less than 0.01), but several animals with minimal hypertension failed to give a depressor response. The declines in arterial pressure were highly correlated with PRA (r = 0.853, P less than 0.01). Aldosterone secretion in hypertensive animals was correlated with PRA (r = 0.851, P less than 0.01). Thus, two-kidney hypertension in the rabbit persists with normal PRA, but during periods of spontaneous sodium depletion, A-II plays a role in the maintenance of the hypertension.     

Haemodynamic and ADH responses to central blood volume shifts in cardiac-denervated humans

Haemodynamic responses and antidiuretic hormone (ADH) were measured during body position changes designed to induce blood volume shifts in 10 cardiac transplant recipients to assess the contribution of cardiac and vascular volume receptors in the control of ADH secretion. Each subject underwent 15 min of a control period in the seated posture, then assumed a lying posture for 30 min at 6 degrees head-down tilt (HDT) followed by 30 min of seated recovery. Venous blood samples and cardiac dimensions (echocardiography) were taken at 0 and 15 min before HDT, 5, 15 and 30 min of HDT, and 5, 15 and 30 min of seated recovery. Blood samples were analysed for haematocrit, plasma osmolality, plasma renin activity (PRA) and ADH. Resting plasma volume (PV) was measured by Evans blue dye and per cent changes in PV during posture changes were calculated from changes in haematocrit. Heart rate (HR) and blood pressure (BP) were recorded every 2 min. In the cardiac transplant subjects, mean HR decreased (BP less than 0.05) from 102 b.p.m. pre-HDT to 94 b.p.m. during HDT and returned to 101 b.p.m. in seated recovery while BP was slightly elevated (P less than 0.05). PV was increased by 6.3% (P less than 0.05) by the end of 30 min of HDT but returned to pre-HDT levels following seated recovery. Plasma osmolality was not altered by posture changes. Mean left ventricular end-diastolic volume increased (P less than 0.05) from 90 +/- 5 ml pre-HDT to 105 +/- 4 ml during HDT and returned to 88 +/- 5 ml in seated recovery. Plasma ADH was reduced by 28% (P less than 0.05) by the end of HDT and returned to pre-HDT levels with seated recovery. PRA was also reduced by 28% (P less than 0.05) with HDT. These responses were similar to those of six normal cardiac-innervated control subjects and one heart-lung recipient. Therefore, cardiac volume receptors are not the only mechanism for the control of ADH release during acute blood volume shifts in man.     

The effect of sodium load on the development of hypertension, plasma renin and kininogen in rats with renal artery constriction

Effects of sodium load on the development of hypertension, plasma renin activity (PRA) and kininogen were studied in rats with renal artery constriction and untouched contralateral kidney. After the operation or sham-operation, 0.9% NaCl or water were given as drinking fluid. A marked hypertension (systolic pressure greater than 150 mmHg) developed in all operated rats on saline, but only in 2/3 of operated rats on water. In none of the sham-operated controls did systolic pressure exceed 150 mmHg during 7 postoperative weeks. Within the operated group on water, hypertensive rats had significantly higher PRA values than normotensive animals (P less than 0.05). Salt load slightly suppressed the PRA in sham-operated rats but not in animals with constriction renal artery, compared to sham-operated controls on water. The operated rats on salt excess had higher plasma kininogen levels than the operated normotensive rats on water (P less than 0.05), but there were no other significant differences in kininogen values between different study groups, regardless of whether blood pressure was increased or not. The results indicate that in this form of hypertension, the high blood pressure can be maintained without any increase in PRA if animals are subjected to a sodium load which sensitizes vascular beds to angiotensin. The increase in plasma kininogen, suggesting suppression of kallikrein-kinin system, is unlikely associated with the increase of blood pressure.     

Effects of NaCl on renin and aldosterone responses to potassium depletion

We have previously suggested that renin secretion is inversely related to the magnitude of absorptive chloride transport in the thick ascending limb of the loop of Henle. Potassium depletion inhibits chloride transport at this site in the nephron. Consequently, we studied the effects of varying sodium and chloride intakes on the renin and aldosterone responses to potassium depletion. Potassium depletion prevented suppression of plasma renin activity (PRA) by dietary NaCl loading and augmented the PRA response to NaCl deprivation. PRA was stimulated (P less than 0.01) by selective chloride (without sodium) deprivation, and potassium depletion did not augment this response. Potassium depletion did not interfere with suppression of PRA by albumin-induced volume expansion. Plasma aldosterone was suppressed by potassium depletion, and the effect of potassium depletion on aldosterone was augmented by NaCl deprivation. In conclusion, the magnitude of PRA stimulation and aldosterone suppression by potassium depletion is modulated by dietary NaCl intake. The results are consistent with the hypothesis that potassium depletion stimulates renin release by inhibiting chloride transport in the loop of Henle.     

Alcohol and the heart. Intense hemodynamic changes associated with alcohol flush in orientals

To evaluate the hemodynamic changes related to alcohol flush, the effects of ethanol intake (0.5 g/kg) were studied by echocardiography and systolic time intervals in 10 Finnish and 9 Japanese healthy volunteers. In 5 Japanese subjects, post-drink facial flush was associated with elevated blood acetaldehyde (peak levels 20-83 mumol/l) and marked cardiocirculatory stimulation. Heart rate was increased directly post ingestion by 65% (p less than 0.01), stroke index by 23% (p less than 0.05), and cardiac index by 106% (p less than 0.05). Diastolic blood pressure was simultaneously decreased by 23% (p less than 0.05), peripheral vascular resistance by 54% (p less than 0.01), and circumferential wall stress by 22% (p less than 0.05); ejection fraction was raised by 26% (p less than 0.01). The other Japanese and the Finnish subjects had no detectable acetaldehyde in blood after ethanol ingestion. The average hemodynamic alterations in them were similar in direction to the changes presented above, but quantitatively 6-10 times smaller (p less than 0.005 for each of these variables). Thus, in Orientals with genetically defective acetaldehyde oxidation, ingestion of even small amounts of alcohol evokes intense enhancement of left ventricular function, probably because of acetaldehyde-induced catecholamine release and peripheral vasodilation.     

Plasma immunoreactive atrial natriuretic peptide and vasopressin after ethanol intake in man

To study the mechanisms of alcohol-induced diuresis, the plasma concentration of immunoreactive atrial natriuretic peptide and arginine vasopressin, serum sodium and osmolality, plasma renin activity and aldosterone, urinary sodium and volume, free water clearance, blood pressure and heart rate were measured in seven healthy men after oral intake of ethanol (1.5 g kg^-1 in 6 h). Serum ethanol levels increased to 27 ± 4 mmol 1^-l (mean ± SD) in 30 min and remained detectable for 14 h. Serum osmolality rose from 280±10 to 340 ± 4 mosm kg^-1 in 2 hours (P < 0.01) and was 300 ± 4 at 14 h (P < 0.01). Formation of hypotonic urine began after the alcohol intake and resulted in a net loss of 0.9 ± 0.1 kg water in 2 h. Free water clearance increased from -3.4 ± 1.4 to 2.8 ± 1.5ml min^-l in 2 h (P < 0.01). Plasma immunoreactive arginine vasopressin decreased from 5.7 ± 2.1 to 3.3 ± 1.3 ng 1^-1 (P = 0.05) in 30 min and increased to 17 ± 25 and 12±10 ng 1^-1 at 6 and 12 h, respectively (P < 0.05 for both). Plasma immunoreactive atrial natriuretic peptide levels decreased from 17 ± 9 to the minimum of 11 ± 3 ng 1^-1 in 2 h (P < 0.01) and returned to the initial levels in 6 h. Serum sodium, plasma renin activity and plasma aldosterone increased maximally by 4 ± 2 , 165 ± 153 and 143 ± 101 % (P < 0.01 each) during 1–6 h. No changes in blood pressure were observed during the ingestion period, but the heart rate rose significantly from 70 min^-1 at 6 p.m. to 95 min^-1 at 12 p.m. We conclude that ethanol intake in relation to serum ethanol levels caused in the first phase a rapid increase in osmolality which was associated with a decrease in plasma immunoreactive arginine vasopressin. This caused hypotonic diuresis and increased free water clearance followed by volume contraction which evidently led to decreased plasma immunoreactive atrial natriuretic peptide. Serum osmolality was significantly elevated during the whole experiment and serum sodium 1–2 h after the ethanol intake. This was associated with the return of plasma immunoreactive atrial natriuretic peptide to initial levels after 6 h, the increase in plasma immunoreactive arginine vasopressin levels and reduced diuresis after 2 h. Our results suggest that ANP is not responsible for the diuresis seen after the alcohol intake.     

Effect of acute acidosis and alkalosis on leucine kinetics in man.

The effects of acute pH changes on whole body leucine kinetics (1-13C-leucine infusion technique) were determined in normal subjects. Plasma insulin, glucagon, and growth hormone concentrations were kept constant by somatostatin and replacement infusions of the three hormones. When acidosis was produced by ingestion of NH4Cl (4 mmol kg-1 p.os; n = 8) arterialized pH decreased within 3 h from 7.39 +/- 0.01 to 7.31 +/- 0.01 (P less than 0.001) and leucine plasma appearance increased by 0.13 +/- 0.04 mumol kg-1 min-1 (P less than 0.02); in contrast, when alkalosis was produced by intravenous infusion of 4 mmol kg-1 NaHCO3 (n = 7, pH 7.47 +/- 0.01), leucine plasma appearance decreased by -0.09 +/- 0.04 mumol kg-1 min-1 (P less than 0.01 vs. acidosis). Whole body leucine flux also increased during acidosis compared to alkalosis (P less than 0.05), suggesting an increase in whole body protein breakdown during acidosis. Apparent leucine oxidation increased during acidosis compared to alkalosis (P = 0.05). Net forearm leucine exchange remained unaffected by acute pH changes. Plasma FFA concentrations decreased during acidosis by -107 +/- 67 mumol l-1 (P less than 0.05) and plasma glucose increased by 1.90 +/- 0.25 mmol l-1 (P less than 0.02); in contrast, alkalosis resulted in an increase in plasma FFA by 83 +/- 40 mumol l-1 (P less than 0.02; P less than 0.01 vs. acidosis), suggesting an increase in lipolysis; plasma glucose decreased compared to acidosis (P less than 0.01). The data demonstrate that acute metabolic acidosis and alkalosis, as they occur in clinical conditions, influence protein breakdown, and in the opposite direction, lipolysis.     

Myoglobin and enzyme adaptations in erector spinae muscles in thoracal scoliosis

Bilateral biopsies from the erector spinae muscles were taken during surgery from 10 females and two males (mean age 14, range 13-17 years) with thoracal scoliosis for 6 years (range 2-11 years). The biopsies were analysed for myoglobin (MYO), citrate synthase (CS) and creatine kinase MB (CK-MB). The severity of scioliosis was estimated by Cobb's angle, the greater the angle the more severe the disease. The convex/concave side ratio (CVX/CCV) was for CS 1.3 +/- 0.4 (P less than 0.01), CK 0.9 +/- 0.1 (P less than 0.05), CK-MB 1.6 +/- 0.4 (P less than 0.01) and for MYO 1.1 +/- 0.2 (P greater than 0.05). No significant correlations were found between the CVX/CCV for CS, CK or CK-MB on the one hand and the Cobb's angle on the other. The CVX/CCV for MYO was, however, directly related to the angle (r = 0.80, P less than 0.01). For the lower range of angles (less than or equal to 59 degrees) the CVX/CCV for MYO was below unity (0.88, P greater than 0.05) and for the larger angles (greater than 59 degrees) above unity (1.23, P less than 0.05). In conclusion, a dissociation in the adaptive response of m. erector spinae in scoliosis between mitochondrial enzyme and myoglobin content was demonstrated.     

Immunomodulatory effects of pulmonary surfactant on natural killer cell and antibody-dependent cytotoxicity.

Alveolar natural killer (NK) cells are functionally weak compared to their blood and interstitial counterparts. Having previously demonstrated that pulmonary surfactant suppresses lymphocyte responses to a variety of stimuli we sought in this study to determine if surfactant exerts a similar suppressive effect on cytotoxic function. Lipids were purified from the bronchoalveolar lavage (BAL) fluid from normal human volunteers. Human peripheral blood lymphocytes (n = 10 subjects) were cultured overnight in the presence or absence of purified BAL lipids (0.2 mg/ml), or pure preparations of phosphatidylcholine (PC), phosphatidylethanolamine (PE), and phosphatidylglycerol (PG) (0.4 mg/ml). Standard NK and antibody-dependent cytotoxicity (ADCC) assays were performed using K562 and Chang target cells. The pooled BAL lipids significantly suppressed both NK (P less than 0.01) and ADCC (P = 0.01) activity in a dose-dependent manner. Whereas pure PC did not exert a significant effect, PG significantly suppressed (P less than 0.01) and PE significantly enhanced (P less than 0.01) both cytotoxic functions. There was no change in the expression of leu 7 or 11b antigens by lymphocytes after culture in BAL lipids. These results suggest that under normal circumstances pulmonary surfactant may suppress alveolar cytotoxic responses but that imbalances in the phospholipid profile might affect this immunoregulatory property.     

Influence of glucose and fructose ingestion on the capacity for long-term exercise in well-trained men

The aim of the present study was to examine the influence of glucose and fructose ingestion on the capacity to perform prolonged heavy exercise. Eight well-trained healthy volunteers exercised on a bicycle ergometer at 68 +/- 3% of their VO2 max until exhaustion, on three occasions, with 8-day intervals. During the exercise they ingested either glucose (250 ml, 7%), fructose (250 ml, 7%) or water (250 ml) every 20 min in a double-blind randomized study design. Arterial blood samples were collected at rest and during exercise for the determination of substrates and hormones. Muscle glycogen content (m. quadriceps femoris) was measured before and after exercise. The duration of exercise lengthened with repeated exercise (3rd test: 136 +/- 13 min v. 1st test: 110 +/- 12 min, P less than 0.01). Corrected for the sequence effect, total work time until exhaustion was significantly longer with glucose (137 +/- 13 min) than with either fructose (114 +/- 12 min) or water (116 +/- 13 min) (both P less than 0.01). When glucose or fructose was ingested, the arterial plasma glucose concentration was maintained at the normoglycaemic level; with water ingestion, plasma glucose values fell during exercise in seven subjects and remained at the resting level in the eighth subject. The muscle glycogen concentration was 467 +/- 29 mmol kg d.w.-1 at rest and fell to approximately half the initial value at exhaustion. In the subgroup of seven subjects in whom glucose values decreased with water intake, the mean rate of glycogen degradation was significantly lower (P less than 0.05) with the ingestion of glucose (1.3 +/- 0.4 mmol kg d.w.-1 min-1) as compared to fructose (2.1 +/- 0.5 mmol kg d.w.-1 min-1) or water (2.3 +/- 0.5 mmol kg d.w.-1 min-1). Intermittent glucose ingestion (3 X 17.5 g h-1) during prolonged, heavy bicycle exercise postpones exhaustion and exerts a glycogen-conserving effect in the working muscles. In contrast, fructose ingestion during exercise maintains the glucose concentration at the basal level but fails to influence either muscle glycogen degradation or endurance performance.     

Renin,aldosterone and arterial pressure responses to acute β-adrenergic receptor blockade in hypertensive patients

Summary The effect of acute (intravenous) -adrenergic blockade with propranolol or pindolol on arterial pressure (BP), plasma renin activity (PRA), and plasma concentration of aldosterone (PA) was evaluated in 20 essential hypertensive men. BP, PRA and PA were determined during continuous recumbency overnight (8 p.m. to 6 a.m.) every 30 min. Two groups of patients were observed. Patients of group I exhibited a characteristic day-night rhythm of PRA with low values before midnight and large increases early in the morning. Conversely, no rhythm and very low PRA values were observed in patients of group II. BP was higher in group II than in group I. In group I following intravenous propranolol or pindolol, BP fell within minutes and levels as well as rhythms of PRA were converted to those of group II without treatment. In group II day-night profiles of PRA and BP remained unchanged. Rhythm and concentration of PA in the two groups were not influenced by either drug. In 4 patients of group I infusion of angiotensin II inhibitor did not lower BP. The observations suggest that in the two groups dissimilarities in rhythms of PRA as well as in BP responses to -blockade may reflect differences in neuro-adrenergic tone.     

酒精诱导嗜铬细胞瘤细胞自噬及其与P62作用的关系

目的 采用不同浓度酒精作用于大鼠嗜铬细胞瘤（PC12）细胞,观察细胞自噬发生及其与P62变化的关系。 方法 用四甲基偶氮唑盐比色法（MTT）观察酒精对PC12细胞生存率的影响;间接免疫荧光法检测细胞自噬标志性蛋白LC3和P62的变化;高内涵活细胞成像系统检测细胞LC3荧光强度;透射电镜检测细胞自噬的超微结构;Western blotting方法检测P62蛋白量的表达。 结果 50～800mmol/L浓度酒精对PC12细胞的增殖有显著的抑制作用,呈浓度依赖性。酒精致PC12细胞自噬标志性蛋白LC3在细胞核周围密度增高,并与P62形成点状聚集共定位,其中在200mmol/L浓度酒精作用2h,PC12细胞LC3自噬荧光强度最高;透射电镜也观察到酒精作用的PC12细胞质中自噬体和自噬溶酶体。Western blotting结果显示,不同浓度酒精处理PC12细胞2h,P62蛋白表达量显著增加 (P<0.01);用200mmol/L浓度酒精处理PC12细胞,P62蛋白表达在2h达到最高值。 结论 酒精诱导PC12细胞的自噬作用,P62蛋白参与自噬调控过程。     

Inhibition of angiotensin-converting enzyme for diagnosis of renal-artery stenosis.

To determine its utility as an aid in diagnosis of renovascular hypertension, we administered nonapeptide converting-enzyme inhibitor (CEI) (which inhibits conversion of angiotensin I to angiotensin II) (0.25 mg per kilogram) to 14 unselected hypertensive patients undergoing bilateral renal-vein catheterization. In seven (Group I) predominantly unilateral disease was discovered by angiography (renal-artery stenosis in six and hydronephrosis in one); in the remaining seven (Group II) no rennal-artery abnormality was found. In Group I, mean (+/- S.E.) ratio of involved to uninvolved renal-vein plasma renin activity (PRA) increased from 2.94 +/- 0.91 before to 8.36 +/- 2.94 after CEI (P less than 0.01). In Group II, the ratio (of the initially higher to the lower side) was 1.99 +/- 0.49 before and 1.17 +/- 0.07 after CEI (P greater 0.02). Post-CEI PRA was predicted by pretreatment PRA. Mean blood pressure fell in both groups after CEI, and the decrement was predicted by pre-CEI PRA. These data suggest that CEI can be of use at the time of renal-vein catheterization, serving to increase diagnostic accuracy by increasing the difference in PRA between the two sides when there is unilateral disease.     

A role of fibrinolytic activity in angiogenesis. Quantitative assay using in vitro method

The functional role of the fibrinolytic system in capillary growth was investigated using bovine capillary endothelial cells (BCEs) cultured on a Type I collagen gel matrix, into which the cells migrated to form capillary-like tubular structures. The length of the tubes formed were measured morphometrically using an image analyzer in the absence and presence of fibrinolytic proteases, namely plasminogen, plasminogen activators (PAs) and PA inhibitor (PAI). The addition of plasminogen (25 micrograms/ml) to the gel matrix significantly increased the length of BCE tubes found on the 9th day of culture (p less than 0.01), with a dose-dependent tendency. The simultaneous addition of a basic fibroblast growth factor (bFGF, 10 ng/ml) enhanced this tube formation as early as the 3rd day of culture (p less than 0.01). Cultured BCEs secreted both tissue-type and urokinase-type PAs (tPA and uPA) and PAI-1 into the culture medium, and the secretion of both PAs was enhanced by the addition of bFGF. However, the secreted tPA was composed mostly of an inactive form of tPA.PAI-1 complex, and the PA activity was derived mostly from uPA. Inhibitors of plasmin suppressed the enhancing effect of plasminogen on angiogenesis. In addition, anti-uPA IgG markedly inhibited the enhancing effect of plasminogen on the 4th and 7th days of culture (p less than 0.01), whereas anti-tPA IgG showed an inhibitory tendency only on the 4th day of culture (p less than 0.05). These findings indicate that the plasminogen-PAs system, especially uPA synthesized and secreted by BCEs, plays an important role in regulating angiogenesis.(ABSTRACT TRUNCATED AT 250 WORDS)