Effects of the aldosterone receptor antagonist potassium canrenoate on renal blood flow and urinary output during prolonged increased intraabdominal pressure (IAP) in pigs.

BACKGROUND: Increased intraabdominal pressure can be found after major abdominal trauma and necrotizing pancreatitis and is used during laparoscopic surgery. The purpose of this study was to investigate the effect of the aldosterone receptor antagonist (potassium canrenoate) on renal hemodynamics and urinary output in pigs during increased intraabdominal pressure (IAP). METHODS: The IAP was kept at 30 mmHg for 3 h by instillation of Ringer's solution into the peritoneal cavity. Eight animals were treated with potassium canrenoate and eight animals served as controls. Renal blood flow, hormones in femoral artery blood, and the urinary output were measured. RESULTS: The administration of potassium canrenoate was followed by increased aldosterone concentrations in arterial blood, increased blood concentration of potassium, and increased concentration of sodium in the urine, indicating satisfactory inhibition of aldosterone. Potassium canrenoate did not cause changes in cardiac output and arterial pressure. It did not affect the renal vascular resistance that increased at an IAP of 30 mmHg, or the renal blood flow that remained constant during the experiments. The group treated with potassium canrenoate had higher mean urinary output than the controls, but the difference was not significant. CONCLUSION: Increased IAP in pigs is associated with markedly reduced urinary output and increased serum concentrations of aldosterone. Although the urinary output did not increase significantly, the increased sodium concentration in the urine of canrenoate-treated animals suggests that the high blood level of aldosterone contributes to the oliguria under increased IAP.

Role of angiotensin II under prolonged increased intraabdominal pressure (IAP) in pigs.

BACKGROUND: The aim of the study was to investigate the effect of the angiotensin II receptor antagonist losartan on renal hemodynamics and diuresis in pigs with increased intraabdominal pressure (IAP). METHODS: The IAP was maintained at 30 mmHg for 3 h by intraperitoneal instillation of Ringer's solution. Ten animals were treated with losartan; another 10 animals served as controls. Renal blood flow, hormones in renal vein blood, and diuresis were measured. RESULTS: In control animals, the renal vascular resistance increased renal blood flow remained constant, the blood concentration of aldosterone increased and the diuresis decreased during increased IAP. Losartan prevented the increase in vascular resistance and improved renal blood flow under increased IAP. It also prevented the rise in aldosterone concentration and increased the urine output to baseline level. CONCLUSION: Our results suggest that the renal vasoconstriction associated with increased IAP is due to increased production of angiotensin II. The oliguria associated with increased IAP is probably due, at least partly, to increased reabsorbtion of sodium and water in the renal tubuli caused by increased tissue concentration of aldosterone.

Effect of light exercise on renal hemodynamics in patients with hypertension and chronic renal disease.

OBJECTIVE: Increased physical activity is followed by a stimulation of the sympathetic nervous system and this effect is probably more pronounced in patients with chronic renal failure and hypertension than in healthy controls. The role of sustained exercise in hypertensive patients with chronic renal failure, with and without antihypertensive therapy, is unclear, as is hormonal regulation of the renal hemodynamics. We hypothesized that prolonged low-intensity bicycle exercise would have a greater effect in patients with chronic renal failure than in controls, and that antihypertensive treatment would ameliorate these effects. MATERIAL AND METHODS: Glomerular filtration rate (GFR), effective renal plasma flow (ERPF), mean arterial blood pressure (MAP), norepinephrine (NE) and atrial natriuretic peptide (ANP) were measured in the upright position before and during low-intensity exercise for 2 h in healthy controls (n = 8) and in hypertensive patients with moderately reduced renal function who were not taking antihypertensives (n = 7) or who were receiving treatment with captopril (n = 10), enalapril (n = 6) or verapamil (n = 9). RESULTS: GFR tended to decrease and ERPF decreased significantly in healthy individuals when exercise duration was prolonged from 1 to 2 h. An earlier decline in GFR and ERPF was seen in the renal failure patients compared with the controls. Filtration fraction (FF) increased during exercise in all groups except the group taking enalapril. MAP increased in the captopril group during exercise but was unchanged in the other groups. Treatment with captopril produced a more pronounced and earlier fall in exercise-induced GFR than in untreated controls, while verapamil treatment completely blunted the decline in GFR, with a concomitant increase in plasma ANP. No significant changes were seen in plasma NE levels, but urinary NE excretion increased in controls and captopril-treated patients during exercise. CONCLUSIONS: The results suggest that prolonged low-intensity exercise has a substantially greater effect on renal hemodynamics in hypertensive renal failure patients than in healthy controls, with negligible changes in plasma NE levels. Verapamil treatment seems to ameliorate the renal effects of exercise on GFR in these patients, and this may in part be mediated via a stimulatory effect on ANP.

[Hereditary thyroxin-binding globulin deficiency--changed thyroid function tests]. / Hereditaer tyroksinbindande globulinmangel--endringar i thyreoideafunksjonsprøver.

BACKGROUND: Variation in concentrations of carrier proteins of hormones may influence the effect of the hormones and may cause confusion in the interpretation of laboratory results. MATERIAL AND METHOD: A Caucasian family with a hereditary thyroxin-binding globulin (TBG) deficiency was investigated. 22 persons in two generations had blood tests for TBG, thyrotropin (TSH), three-iodothyronin (T3), thyroglobulin (TG), thyroxin and for free thyroxin (FT4) by two different commercial tests, Delfia and IMx Abbott (IMx). Relevant health information was collected of all persons. RESULTS: Six males had very low T4 values, non-detectable TBG, increased FT4 values on the Delfia test and within normal range on the IMx test. Six females had lower borderline T4 and TBG. All persons were clinical euthyroid. INTERPRETATION: The condition is considered to represent X-chromosome linked inheritance with hemizygote affected males and heterozygote female carriers with intermediate values for T4 and TBG. Commercial test kits for FT4 may present considerably different results in conditions with TBG deficiency. When a high level of measured FT4 combined with normal TSH is found; TBG deficiency should be considered.

Role of endothelin in the circulatory changes associated with small bowel strangulation obstruction in pigs: effects of the endothelin receptor antagonist bosentan.

BACKGROUND: We have previously shown that experimental strangulation obstruction leads to increased release and concentration of endothelin-1 (ET-1) in venous blood from the strangulated bowel loop. The present study focuses on the microcirculatory effects of the released ET-1 in strangulation obstruction. METHODS: In anesthetized pigs strangulation obstruction was induced by increasing pressure in a baby pressure gasket placed around a loop of ileum until venous pressure reached 45 mm Hg. The pigs were randomly allocated into two groups. The nonselective ET(A)/ET(B) antagonist bosentan was administered intravenously (5 mg kg(-1)) to eight pigs (bosentan group) 30 min before strangulation, which was maintained for 90 min. Another eight pigs were treated in same manner except for the bosentan injection (control group). RESULTS: The concentration of ET in arterial and intestinal venous blood increased markedly after intravenous administration of bosentan. Intravenous infusion of bosentan was followed by a reduction in systemic arterial blood pressure. Bosentan reduced vascular resistance and increased blood flow in the normal intestinal mucosa. It also reduced muscularis blood flow in the beginning of the experiment. In strangulated small bowel bosentan inhibited the increase in vascular resistance usually caused by strangulation obstruction. Muscularis blood flow in strangulated small bowel was not affected by bosentan. CONCLUSION: Endothelin is involved in the normal regulation of arterial blood pressure. The increase in vascular resistance associated with strangulation obstruction is caused mainly by locally released endothelin.

Sympathetic nervous system overactivity in hypertensive patients with chronic renal failure--role of upright body position.

OBJECTIVE: The renal functional consequences of an activated sympathetic nervous system and plasma atrial natriuretic hormone (ANP) in various renal diseases are not well described. We hypothesize that norepinephrine (NE) and ANP have antagonizing effects on renal hemodynamics in diseased kidneys. MATERIAL AND METHODS: Plasma NE, ANP. glomerular filtration rate (GFR), effective renal plasma flow (ERPF) and mean arterial pressure (MAP) were measured in the upright position in healthy controls (n = 9) and hypertensive patients with reduced GFR (n =11). The same parameters were compared between healthy controls (n = 6) and hypertensive patients with reduced GFR (n = 6) in upright and supine positions. RESULTS: Upright plasma NE and ANP were significantly elevated in the patients compared with the controls (4.4 +/- 0.4 vs 2.1 +/- 0.2 nmol/l (p < 0.001) and 1.3.5 +/- 2.1 vs 6.9 +/- 1.0 nmol/l (p < 0.01) respectively). With change from upright to supine position plasma NE decreased in the controls (2.2 +/- 0.3 vs 1.7 +/- 0.3 nmol/l) (p < 0.01) and patients (3.8 +/- 0.4 vs 2.6 +/- 0.4) (p < 0.01). Supine ANP increased in controls (5.5 +/- 1.0 vs 8.3 +/- 1.1) (p < 0.01) but not in patients (14.3 +/- 3.8 vs 16.1 +/- 3.8 nmol/l) (p > 0.10). Plasma NE correlated positively with MAP (p < 0.001) and negatively with GFR (p < 0.01) in the upright but not supine position. A positive correlation between NE and ANP was observed in upright (p < 0.001) but not in supine position. ANP correlated negatively with GFR in the upright (p < 0.01) but not supine position. No position dependent changes were seen in GFR and ERPF, but supine filtration fraction (FF) increased insignificantly in the patient group (0.23 +/- 0.02 vs 0.24 +/- 0.02) (p < 0.05). CONCLUSION: Hypertensive patients with reduced GFR have elevated levels of plasma NE and ANP in the upright body position. When the upright and supine positions are compared, plasma NE declines in the supine position in controls and hypertensive renal failure patients. and plasma ANP levels are elevated only in the upright position in hypertensive renal failure patients where the sympathetic nervous system is activated. A significant positive relationship between plasma NE and ANP was observed only in the upright position. The upright body position seems superior to recumbency in the characterization of these hormonal changes in hypertensive chronic renal failure patients.

Long-term central hemodynamic effects at rest and during exercise of losartan in essential hypertension.

BACKGROUND: Losartan reduces blood pressure in patients with essential hypertension, but the long-term central hemodynamic effects at rest and during exercise are not known. METHODS AND RESULTS: After 8 months of losartan treatment (50 to 100 mg daily, mean 82 mg), intra-arterial pressure was reduced from 165/102 mm Hg to 145/91 mm Hg at rest and from 193/104 mm Hg to 179/96 mm Hg during 100 W exercise in 28 patients with essential hypertension. Cardiac index and heart rate remained unchanged, but total peripheral resistance index was reduced 12% to 15%. Stroke index was unchanged at rest but increased 7% to 9% during exercise. Twenty-four-hour ambulatory blood pressure was reduced 10% to 13%. Left ventricular mass was reduced 27% in patients with left ventricular hypertrophy (n = 18). CONCLUSION: Losartan lowers blood pressure by reducing total peripheral resistance at rest and during exercise but cardiac pump function is unchanged or slightly improved. In patients with left ventricular hypertrophy, losartan induces a sizeable reduction in left ventricular mass.

The value of ultrasonography in predicting autoimmune thyroid disease.

Ultrasonography (US) may demonstrate a diffuse reduction in thyroid echogenicity (low-amplitude echoes) in autoimmune thyroid disease (AITD), which includes chronic lymphocytic thyroiditis and Graves' disease, as well as in subacute thyroiditis. The reported occurrence of this finding in AITD varies from 19% to 95%. To assess the validity of diffuse reduction in thyroid echogenicity as a predictor of AITD, 3,077 patients referred for US of the thyroid were examined prospectively with regard to reduced versus normal thyroid echogenicity. The most frequent reasons for referral were goiter, thyroid dysfunction, neck discomfort, and/or difficulty in swallowing. Ultrasonography demonstrated diffuse reduction in thyroid echogenicity in 485 patients. Of these, 452 patients had available records of fine-needle aspiration biopsy (FNAB), and were included in the study. From the remaining patients, with normal thyroid echogenicity, 100 consecutive patients were selected as controls. In 411 of the 452 study patients (90.9%) there was at least one laboratory finding consistent with possible AITD: cytology indicating lymphocytic thyroiditis, 287 of 363 patients (79.1%) with diagnostic specimens; elevated levels of peroxidase antibodies (TPOAb), 225 of 337 (66.8%); elevated thyrotropin (TSH) levels, 290 of 450 (64.4%); or low TSH levels, 79 of 450 (17.6%). The final diagnosis was: chronic autoimmune (Hashimoto's) thyroiditis in 352 patients; Graves' disease in 47 patients; subacute (granulomatous) thyroiditis in 7 patients; toxic nodular goiter in 3 patients; and toxic adenoma in 2 patients. In the remaining 41 patients, those without laboratory results consistent with AITD, the final diagnosis was colloid goiter in 37 and thyroid cancer in 4 patients. In the 100 controls, laboratory results were consistent with possible AITD in 14 patients: elevated TPOAb levels in 5 of 49 patients with retrieved antibody results; lymphocytic thyroiditis in 2 patients; elevated TSH levels in 2 patients; and low TSH levels in 2 patients. In these controls, the final diagnosis was: chronic autoimmune thyroiditis in 7; toxic nodular goiter in 6 patients, and toxic adenoma in 1 patient. The corresponding positive and negative predictive values of reduced thyroid echogenicity as an indicator of AITD were 399 of 452 (88.3% [95% CI, 85% to 91%]), and 93 of 100 (93.0% [95% CI, 88% to 98%]), respectively. Thus, diffuse reduction in thyroid echogenicity was a valid predictor of AITD.

Correlation between fetal sex and human chorionic gonadotropin in peripheral maternal blood and amniotic fluid in second and third trimester normal pregnancies.

BACKGROUND: To study the correlation between fetal sex and human chorionic gonadotropin (hCG) in maternal blood and amniotic fluid. METHOD AND MATERIAL: One hundred and thirty uncomplicated pregnancies, 82 of whom were at sixteen and 48 at thirty-five weeks of gestation. RESULTS: The hCG levels were significantly higher in maternal serum than in amniotic fluid. At 16 weeks there were no sex-related differences in the hCG levels, either in maternal blood or in amniotic fluid. At 35 weeks the hCG levels in maternal blood were significantly higher in pregnancies with female fetuses than in those carrying male fetuses (p<0.004), while in amniotic fluid the hCG levels tended to be slightly higher in the female group than in the male. In pregnancies with female fetuses the hCG levels in maternal blood were significantly higher at 35 than at 16 weeks (p<0.02), while in pregnancies with male fetuses the levels were highest at 16 weeks. For both sexes the hCG levels in amniotic fluid were significantly higher at 16 than at 35 weeks of pregnancy (p<0.001). Whereas a significant correlation between hCG levels in maternal blood and amniotic fluid was seen at 16 weeks of gestation for both sexes (p<0.01 and R value 0.45 for males and 0.41 for females), no correlation was observed at 35 weeks. CONCLUSION: This study shows a significant correlation between hCG and fetal sex at third trimester of gestation only, possibly caused by a gender factor and a shift in synthesis and/or in metabolism of hCG from the second to the third trimester.

Similar central hemodynamics in salt-sensitive and salt-resistant hypertensive patients.

Salt may be involved in the pathogenesis of essential hypertension but no agreement has been reached on how salt might exert its blood pressure control. One reason for the conflicting results could be differences in response to changes in salt intake--i.e. between salt-sensitive and salt-resistant subjects. Hypertension reflects a hemodynamic disturbance: mainly an increase in total peripheral resistance. In order to determine whether central hemodynamics is different in salt-sensitive and salt-resistant essential hypertension, a study was carried out on 37 patients aged 31-63 years with mean casual blood pressure 165/104 mmHg. Based on an increase in ambulatory 24-h mean blood pressure of > or = 10% after one week of dietary salt loading (260 mmol NaCl/24 h) following a one-week salt depletion period (60 mmol NaCl/24 h), 7 patients (19%) were classified as salt sensitive and 30 patients (81%) as salt resistant. Before the salt-sensitivity test, while patients were on their habitual salt intake (160 mmol NaCl/24 h), central hemodynamics (intra-arterial pressure, cardiac output by dye dilution, heart rate by electrocardiogram, and total peripheral resistance) was examined at rest and during bicycle exercise. None of the central hemodynamic variables were different between the two groups, despite a marked difference in blood pressure response to one week of salt loading between the salt-sensitive and the salt-resistant groups (27/9 mmHg vs -2/1 mmHg). Furthermore, no statistically significant differences were observed in neurohumoral variables or echocardiographic indices of left ventricular dimensions between the two groups. Owing to the invasive hemodynamic procedure, central hemodynamics was not restudied during high- or low salt intake. It is concluded that there is no difference in central hemodynamics in salt-sensitive and salt-resistant hypertensive patients when they are on their habitual salt diet.

Factors influencing reduction in blood pressure and left ventricular mass in hypertensive type-1 diabetic patients using captopril or doxazosin for 6 months.

The effect of doxazosin versus captopril on blood pressure, albuminuria, and left ventricular mass was studied in 33 hypertensive type-1 diabetic patients randomized to 6 months treatment with captopril (17 patients, mean daily dose 100 mg) or doxazosin (16 patients, mean daily dose 9 mg). Casual and 24-h ambulatory blood pressure (24hBP) were reduced from 163/95 to 144/83 mm Hg and 152/86 to 145/81 mm Hg, respectively, in the captopril group, and from 160/93 to 145/86 mm Hg and 156/86 to 147/79 mm Hg in the doxazosin group (all P < .05). The achieved 24hBP on treatment was positively associated with pretreatment levels of glycosylated hemoglobin (HbA1c) and plasma atrial natriuretic peptide (r = 0.53 and 0.59, respectively, both P < .01). Albuminuria did not change significantly in either group. Left ventricular hypertrophy was present in 13 patients (7 in the captopril and 6 in the doxazosin group). Left ventricular mass was reduced by an average of 27% and 23%, respectively, in these patients (both P < .01), but did not change significantly in patients without left ventricular hypertrophy. The reduction in left ventricular mass was positively associated with the presence of baseline left ventricular hypertrophy and inversely with dietary sodium intake and achieved casual blood pressure on treatment (R2 = 0.59, P < .001). We conclude that doxazosin and captopril used for 6 months are equally effective in reducing blood pressure and left ventricular hypertrophy in hypertensive type-1 diabetic patients; the antihypertensive effect is closely related to glycemic control; and dietary sodium intake and achieved casual blood pressure after treatment are independent determinants of the reduction in left ventricular mass seen in these patients.

Pituitary dwarfism in the R271W Pit-1 gene mutation.

UNLABELLED: The Pit-1 gene encodes the POU-domain transcription factor Pit-1 which is important for the differentiation of the anterior pituitary and regulation of the PRL, GH and TSH genes. As a member of the POU domain transcription factors, Pit-1 contains a DNA-binding region, consisting of a POU-specific domain and a POU homeodomain. Mutation of the Pit-1 gene causes hypoplasia of the pituitary gland and deficiencies of GH, PRL and TSH. In a DNA sample from a 3-month-old girl with severe growth deficiency from birth, single stranded conformational polymorphism analysis of the Pit-1 gene identified a gel shift in exon 6. DNA-sequencing disclosed a single base mutation in codon 271 (CGG to TGG) that changes arginine to tryptophan (R271W) in the POU homeodomain. The patient presented distinct facial features with prominent forehead, marked mid-facial hypoplasia with depressed nasal bridge, deep-set eyes and a short nose with anteverted nostrils. MRI examination showed a hypoplastic pituitary gland. Low serum GH did not respond to insulin-arginine provocation or GHRH tests. PRL levels below the detection limit did not increase in response to a TRH test. T4 and free T4 was below detection limit (< 20 nmol/l and < 4 pmol/l). TSH was 2.0 mU/l and showed a blunt response to 6.0 mU/l following TRH test. TBG was normal. In spite of inappropriately low TSH and very low T4, T3 was in the low normal range (1.4-1.6 nmol/l) and she was clinically euthyroid. The thyroid function tests are consistent with increased monodeiodination activity and increased conversion of T4 to T3, possibly related to the Pit-1 gene mutation. GH and T4 treatment resulted in catch-up growth continued during 5 years of therapy. CONCLUSION: Reports of nine other cases of R271W mutations of different populations as well as the present Norwegian patient suggest codon 271 of exon 6 to be a "hot spot" for Pit-1 mutations. To enable rapid and simple detection of this type of de novo mutation we have designed a specific amplification-created-restriction-site assay to check for the R271W mutation in patients suspected to have this rare form of genetic defect in growth hormone production.

Factors influencing LVM in hypertensive type-1 diabetic patients.

Diabetes mellitus is associated with a high prevalence of hypertension and left ventricular hypertrophy (LVH), and a causative relationship with abnormal sodium metabolism in diabetic patients has been suggested. Factors influencing left ventricular mass (LVM) were assessed in 30 hypertensive type-1 diabetic patients, mean age 46 +/- 9 (range 24-67) years, with a mean duration of diabetes and hypertension of 19 +/- 10 and 6 +/- 5 years, respectively. In the total study population, casual blood pressure was 163/94 +/- 24/10 mmHg and 24 h blood pressure was 155/87 +/- 17/8 mmHg. Twenty-four-hour urine samples were obtained to measure daily albumin excretion (0.77 +/- 1.06 g) and dietary sodium intake was assessed as 24 h sodium excretion (173 +/- 77 mmol). Creatinine clearance averaged 1.41 +/- 0.53 ml/s. LVM determined by echocardiography was 221 +/- 74 g (range 104-408 g) and 33% of the patients had LVH. Multiple regression analysis identified dietary sodium intake and plasma atrial natriuretic peptide as independent predictors of LVM (R2 = 0.52, p < 0.001). No significant association was found between LVM and blood pressure or albuminuria. The results propose dietary sodium intake as an important factor in the development of LVH in hypertensive type-1 diabetic patients.

Salt sensitivity in hypertensive type-1 diabetes mellitus.

UNLABELLED: As sodium retention has been proposed as a causal factor in the development of hypertension in diabetic patients, a high incidence of salt sensitivity has been suggested. To evaluate the influence of dietary sodium intake on blood pressure, casual and 24-h blood pressure was measured in 30 hypertensive type-1 diabetic patients aged 24-67 (mean 46) years while they were on habitual diet, after 6 days of low-sodium diet (50 mmol/day), and after 6 days of high-sodium diet (250 mmol/day). Nine patients (30%) who increased their 24-h mean blood pressure by more than 10% when going from low- to high-sodium intake were classified as salt sensitive; the others as salt resistant. The salt sensitive group had a significantly lower urinary excretion of dopamine at baseline, and a higher diuresis and a more pronounced decrease in 24-h blood pressure during salt depletion (all p < 0.01). Low-sodium diet reduced casual and 24-h blood pressure by 4% in the total study population compared with 9% in the salt sensitive group (p < 0.01). There was no difference in glomerular filtration rate, filtration fraction, proteinuria or urinary sodium excretion between the groups. CONCLUSIONS: Sodium restriction more effectively reduces blood pressure in the salt sensitive minority of hypertensive type-1 diabetic patients irrespective of renal function. The incidence of salt sensitivity is not increased in hypertensive type-1 diabetic patients compared with essential hypertensive patients.

Unchanged central hemodynamics after six months of moderate sodium restriction with or without potassium supplement in essential hypertension.

Sodium (Na) restriction and potassium (K) supplementation has been recommended as treatment of essential hypertension but the mechanism by which these may reduce blood pressure (BP) is unknown. We examined if moderately reduced Na intake, combined with a low-Na/high-K salt alternative (Pansalt: NaCl 57%, KCl 28%, MgSO4 12%) as substitute for standard table salt, induced clinically significant BP reduction in hypertensive patients and, if this therapy reduced total peripheral resistance. After a 2-month control period 40 patients aged 21-67 years with mean casual BP 156/103 mmHg were given a salt restricted diet (120 mmol Na/24 h) for 6 months. In addition, they were randomised in a double-blind manner to receive either Pansalt (P-group) or standard NaCl (S-group) as table salt in small amounts. Cardiac output was measured by dye dilution. Daily Na excretion was similarly reduced (20%) in both groups while K excretion was slightly increased in the P-group and reduced in the S-group (difference p < 0.05). No large changes occurred in 24-h ambulatory BP (by Accutracker II) or intraarterial pressure (through a brachial artery catheter) at rest or during exercise while casual BP was reduced (p < 0.05) 13/8 mmHg in the P-group and 8/5 mmHg in the S-group. While cardiac output was slightly reduced at rest and during 50W exercise in the P-group, no significant changes were seen in total peripheral resistance in either group. Thus, moderate reduction in Na intake, with or without addition of K, is not sufficient to induce significant long-term intraarterial or 24-h ambulatory BP changes in essential hypertension. Without BP changes invasively determined central hemodynamics remains remarkably stable over a 6-month period.

Salt sensitive essential hypertension evaluated by 24 hour ambulatory blood pressure.

Thirty men with essential hypertension were examined at three different levels of sodium intake, containing 135, 44 and 290 mmol sodium per day, respectively. Ten patients who increased their 24 hour mean ambulatory blood pressure 10% or more when going from low to high sodium intake were defined as salt sensitive, the others as salt resistant. The casual and 24 hour ambulatory blood pressure measurements defined partly different patients as salt sensitive. In multiple regression analysis, salt sensitivity was associated with an increase in diuresis during low sodium intake, demonstrating a dissociation between water and sodium excretion during salt depletion in the salt sensitive group. The change 24 hour ambulatory blood pressure during salt repletion was positively correlated to the increase in the atrial natriuretic peptide (p < 0.01), and inversely correlated to the plasma concentration of atrial natriuretic peptide after salt depletion (p < 0.01). No difference in plasma norepinephrine, renin, aldosterone, plasma volume, blood volume or 24 hour sodium excretion was found between salt sensitive and salt resistant subjects. We conclude that salt sensitivity is difficult to describe as an entity, but seems to be associated with lower levels of atrial natriuretic peptide and a different response to salt depletion.

The Bergen Blood Pressure Study: inappropriately low levels of circulating atrial natriuretic peptide in offspring of hypertensive families.

Plasma atrial natriuretic peptide (ANP), plasma and 24-h urine catecholamines, plasma renin activity (PRA), and serum aldosterone were studied in offspring of hypertensive and normotensive families [n = 82; age 37 +/- 7 years (mean +/- SD)]. Despite higher age, higher blood pressure, and higher urine excretion of catecholamines--all of which are factors associated with increased ANP levels--the mean basal plasma ANP concentration tended to be lower in offspring of hypertensive than normotensive families. The same pattern was found in all age-tertiles, and the between-group difference was statistically significant in subjects aged 34-39 years (p < 0.01). Also, the family history of hypertension was associated with low ANP levels after covariate adjustment (p < 0.05). The 24-h urine excretion of epinephrine and norepinephrine tended to be higher in offspring of hypertensive than normotensive families while the morning venous plasma levels were similar. The ratio between venous plasma ANP and norepinephrine was lower in offspring of hypertensive than normotensive families (p < 0.05). PRA, serum aldosterone level, and 24-h urine excretion of dopamine did not differ significantly between groups. Inappropriately low basal plasma ANP concentrations and low plasma ANP/norepinephrine ratios may be related to the development of essential hypertension in offspring of hypertensive families.

The acute effects of induced tachycardia on coronary sinus and arterial plasma levels of atrial natriuretic peptide and on arterial catecholamines.

Atrial natriuretic peptide (ANP) was measured in coronary sinus (CS) plasma in seven patients with induced tachycardia. Right atrial pressure (RAP) and femoral artery (FA) levels of ANP, noradrenaline (NA) and adrenaline (A) were measured before and after 5 min with tachycardia. During tachycardia, ANP in CS plasma increased from 381 +/- 273 (mean +/- SD) to 1376 +/- 1191 pmol l-1 (p < 0.0001), and ANP levels in FA plasma from 89 +/- 48 to 231 +/- 151 pmol l-1 (p < 0.005). A significant increase was observed for peak RAP, whereas mean RAP remained unaltered. While no correlation existed between the increase in CS plasma ANP level and RAP, significant correlations were found between the changes in FA plasma ANP and RAP, and between FA plasma levels of ANP and NA. Following tachycardia, significant correlations were found both between ANP in CS and FA plasma and between the changes in these plasma levels. Whereas the changes in FA plasma levels of ANP during tachycardia seems dependent of RAP and arterial plasma levels of NA, the CS plasma ANP level appears to be independent of the two factors, probably because CS plasma ANP are drained mainly from the left side of the heart.

The Bergen blood pressure study: sodium intake and ambulatory blood pressure in offspring of hypertensive and normotensive families.

Sodium intake, estimated by the 24-h urine sodium excretion, was assessed in 39 offspring of hypertensive families and 37 offspring of normotensive families. The family history of hypertension or normotension was defined according to parental BP data from two surveys conducted 27 years apart. Urine-sodium excretion was similar in offspring of hypertensive and normotensive families, averaging 136 and 137 mmol/24 h, respectively. Monitored by non-invasive methodology in the urine sampling period, the average 24-h ambulatory blood pressure (BP) was approximately 10/10 mmHg higher in offspring of hypertensive than normotensive families. The clinically and statistically significant differences in BP between groups could not be explained by differences in sodium intake. After adjustment for confounding variables, the BP was not associated with the sodium excretion in the material as a whole or in either offspring group.

Can disulfiram potentiate the dexamethasone suppression test in depressive patients?

Transient DST non-suppression during disulfiram-treatment was fortuitously observed in a depressed patient. A disulfiram-potentiated DST (DSTd) was constructed by giving 800 mg disulfiram on the dexamethasone and postdexamethasone days. DST and DSTd were compared intraindividually in 21 patients and 14 controls. Disulfiram-potentiation was significant in constantly depressed patients, and in questionable controls due to possible subclinical depression or somatic factors which may cause 'false-positive' results. It did not occur in depressed patients during marked improvement or long-term recovery, and not in accurately screened controls. DSTd was significantly correlated with depression ratings, whereas DST was not.