Hormonal changes in patients with severe chronic congestive heart failure treated by ultrafiltration.

Plasma atrial natriuretic peptide (ANP), antidiuretic hormone (ADH), plasma renin activity (PRA), and circulatory haemodynamics were studied in five patients with chronic congestive heart failure undergoing ultrafiltration on two consecutive days. The patients were in the New York Heart Association class IV, and were considered candidates for heart transplantation. A mean of 3.3 +/- 0.5 litres of fluid was removed during each ultrafiltration. Plasma ANP concentration remained unchanged during ultrafiltration: 369 +/- 151 pg/ml at start and 316 +/- 116 pg/ml at the end, while plasma ADH concentration and PRA increased from 5.1 +/- 2.1 to 7.5 +/- 3.4 pg/ml (P less than 0.02), and 5.9 +/- 3.0 to 7.7 +/- 3.2 ng/ml (P less than 0.03) respectively (n = 10). After treatment, plasma ADH and PRA declined to baseline values within 1 h. Pulmonary artery, pulmonary capillary wedge, and right atrial pressures decreased significantly, while blood pressure and heart rate remained constant during ultrafiltration. A volume of 3.3 +/- 0.5 litres of fluid was removed, and caused an increase in colloid osmotic pressure from 22.0 +/- 3.0 to 33.7 +/- 3.9 mmHg (P less than 0.02). It was unexpected that plasma ANP concentration did not decline. Due to long-standing severe heart failure the atrial wall may have lost some of its elastic properties, resulting in less ability to adapt to reduced filling pressures. Accordingly, atrial wall stretch remained unchanged, explaining the constant ANP levels. Ultrafiltration treatment caused an increased responsiveness to diuretic therapy, and four patients survived long enough to receive heart transplants.     

Effects of ciclosporin on plasma renin activity, catecholamines and prostaglandins in patients with idiopathic uveitis

Animals and humans undergoing treatment with ciclosporin (CS) show a reversible increase in renal vascular resistance and a decrease in glomerular filtration rate. The causes of these abnormalities have not yet been established. We evaluated the effects of a 1-week treatment with CS on creatinine clearance, renal arachidonic acid metabolites, plasma renin activity (PRA), plasma aldosterone levels, urinary excretion and plasma levels of catecholamines in 7 patients with idiopathic uveitis. We show that CS treatment induces a significant (p less than 0.05) decrease in creatinine clearance (from 132 +/- 0.5 to 108 +/- 8 ml/min); urinary 6-keto-PGF1 excretion (from 17.8 +/- 4.9 to 10.9 +/- 3.3 ng/mmol creatinine), urinary thromboxane B2 excretion (from 7.0 +/- 1.0 to 3.6 +/- 0.9 ng/mmol creatinine), upright PRA (from 4.2 +/- 0.9 to 2.3 +/- 0.8) and supine PRA (from 2.0 +/- 0.5 to 1.1 +/- 0.3). We found no change in plasma aldosterone levels and plasma levels and urinary excretion of catecholamines. We suggest that the reversible renal vasoconstriction observed in patients treated with CS may be induced by inhibition of renal prostacyclin synthesis. In this setting inhibition of PRA and angiotensin II formation may impair autoregulation of effective filtration pressure and therefore glomerular filtration rate.     

Water immersion-induced alterations of plasma atrial natriuretic peptide level and its relationship to the renin-angiotensin-aldosterone system and vasopressin secretion in acute and chronic renal failure

Water immersion (WI)-induced alterations of circulating plasma volume (PV), plasma renin activity (PRA), plasma levels of aldosterone (Ald), vasopressin (AVP) and atrial natriuretic peptide (ANP) were examined in 12 patients with noninflammatory acute renal failure (ARF) at the anuric/oliguric phase, in 20 hemodialyzed patients with chronic renal failure and in 15 healthy subjects. Patients with acute and chronic renal failure showed significantly elevated basal ANP concentrations (138.67 +/- 12.88 and 295.8 +/- 21.87 pg/ml, respectively) as compared with normals (74.54 +/- 4.1 pg/ml) and significantly elevated PRA (20.85 +/- 3.24 and 6.60 +/- 0.94 ng/ml/h, respectively versus 2.33 +/- 0.31 ng/ml/h), plasma levels of Ald (16.11 +/- 1.26 and 18.11 +/- 1.58 ng/dl, respectively versus 12.71 +/- 1.03 ng/dl) and AVP (6.95 +/- 0.62 and 6.08 +/- 0.54 pg/ml, respectively versus 2.68 +/- 0.48 pg/ml). After 2 hrs of WI a significant decline of PRA, Ald and AVP but an increase of ANP was noted in all examined groups. The absolute WI-induced increase in plasma ANP was significantly less marked in uremic patients than in normals. The endocrine profile of patients with ARF differed only quantitatively from that of patients with CRF both under basal and WI conditions. WI was followed by a significant increase of PV which was significantly more marked in patients with ARF (+ 16.42 +/- 1.73%) than in CRF (10.57 +/- 0.37%) and in normals (+11.3 +/- 1.6%). Only in healthy subjects a significant correlation was found between WI-induced changes of PV and ANP, PRA and Ald, and between PRA and AVP.(ABSTRACT TRUNCATED AT 250 WORDS)     

Increased plasma levels of immunoreactive human atrial natriuretic factor in primary IgA nephropathy

The plasma concentration of the immunoreactive (IR) human atrial natriuretic factor (hANF) was measured in 17 patients with primary IgA nephropathy (IgAN) (9 normotensive and 8 hypertensive subjects without impairment of renal function). Furthermore, correlations with the renin-angiotensin II-aldosterone system and hemodynamic alterations were studied. The mean value of IR-hANF was significantly (p less than 0.002) higher in normotensive IgAN patients (68.2 +/- 14.6 pg/ml) than in controls (48.8 +/- 11.5 pg/ml), while it was slightly and not significantly elevated in hypertensive IgAN patients (58.5 +/- 8.4 pg/ml). In the latter the mean plasma renin activity (PRA) was significantly increased (0.92 +/- 0.30 ng/ml/h; p less than 0.002), while in normotensive IgAN patients (0.68 +/- 0.58 ng/ml/h) no difference was observed. Plasma aldosterone levels showed the same behavior pattern as those of PRA. Hemodynamic studies showed that the mean values of the cardiac index (CI) were significantly (p less than 0.002) high in both normotensive (3.55 +/- 0.5 l/min/m2) and hypertensive (3.32 +/- 0.47 l/min/m2) patients, while a significant reduction in the total peripheral resistance index (TPRI) in normotensive (2171 +/- 349 dyn/s/cm-5/m2; p less than 0.02) and a significant increase in hypertensive (2959 +/- 440 dyn/s/cm-5/m2; p less than 0.05) patients were observed. The mean arterial pressure (MAP) had a positive correlation with the TPRI and an inverse correlation with the IR-hANF.(ABSTRACT TRUNCATED AT 250 WORDS)     

Role of renal prostaglandin E2 in chronic renal disease hypertension

The role played by renal prostaglandin E2 in the maintenance of hypertension in chronic renal disease has been investigated through studying the response of body weight, blood pressure, glomerular filtration rate (GFR), 24-hour natriuresis, plasma renin activity (PRA), plasma aldosterone and urinary PGE2 excretion to the administration of indomethacin (2mg/kg daily, during 3 days). A group of 37 patients diagnosed as having chronic renal parenchymatous disease with creatinine clearance above 25 ml/min was included in the study. 21 of them were hypertensive (BP greater than 160/95). 27 normotensive volunteers were also studied and considered as the control group. The initial study disclosed similar levels of PGE2, PRA and plasma aldosterone in volunteers, normotensive patients and hypertensive patients, although the sodium intake was lower in the last two groups. A positive correlation between PRA and urinary PGE2 was found both in normotensive (r = 0.507, p less than 0.01) and in hypertensive patients (r = 0.609, p less than 0.01). The administration of indomethacin induced a diminution of PRA, plasma aldosterone and urinary PGE2 levels together with an increase in diastolic blood pressure (p less than 0.05-0.01) in both volunteers and patients. The remaining parameters measured did not change in volunteers or in normotensive patients. On the contrary, in hypertensive patients, during indomethacin administration, lower values of creatinine clearance (p less than 0.005) and 24-hour natriuresis (p less than 0.05) together with an increase in body weight (p less than 0.01) were observed. These results point to the existence of a protective role of renal prostaglandin E2 upon renal function when hypertension appears in the course of chronic renal parenchymatous disease.     

Aldosterone in congestive heart failure: analysis of determinants and role in sodium retention.

In patients with congestive heart failure (CHF), the role of aldosterone in the abnormal sodium (Na+) retention and the determinants of plasma aldosterone (PA) including plasma atrial natriuretic factor (hANF), plasma renin activity (PRA), and plasma potassium (K+) have not been fully elucidated. We therefore studied the effect of the specific aldosterone antagonist, spironolactone, on urinary Na+ and K+ excretion and plasma hormone responses in 6 Na(+)-retaining CHF patients. After withdrawal of diuretics 4 days prior to the study, the CHF patients were placed on a Na+ intake of 100 mmol/day for 9 days. Spironolactone, 200 mg p.o. bid, was administered for the last 4 days of the 9-day study period. PRA and norepinephrine increased with spironolactone treatment (both p less than 0.05). Plasma hANF before spironolactone was significantly elevated and decreased during spironolactone therapy (p less than 0.05). Urinary Na+ excretion significantly increased during spironolactone administration and the positive Na+ balance was reversed in the CHF patients. Moreover, the urine Na+:K+ concentration ratio significantly increased during spironolactone administration. Analysis of the relationship between PA, plasma K+, PRA, and plasma hANF indicated that PRA is the primary determinant of PA in patients with CHF. Thus, the present results indicate that the renin-angiotensin-aldosterone system is an important mediator of Na+ retention in CHF, as evidenced by the reversal of the positive Na+ balance with a specific aldosterone antagonist. This natriuretic effect can be demonstrated in the presence of potential antinatriuretic influences including stimulation of the renin-angiotensin and sympathetic nervous systems and a decrease in plasma hANF.     

Role of dietary potassium in the hyperaldosteronism and hypertension of the remnant kidney model

The remnant kidney model of progressive renal disease is marked by arterial hypertension, especially when produced by nephrectomy and partial infarction. Hyperaldosteronism sustains much of the hypertension, but the stimuli to the increased aldosterone levels are uncertain. It is hypothesized that the hyperaldosteronism attending this model stems from the combination of fixed dietary potassium load in the face of reduced filtration on the one hand, and persistent renin secretion from the scarred remnant kidney on the other. This hypothesis predicted that dietary potassium restriction would lower aldosterone and BP in this model. To test this prediction, two groups of rats with a remnant kidney were studied. Group 1 consumed 0.4 +/- 0.06 mEq (mean +/- SD) of potassium chloride daily, and group 2 ate 4.8 +/- 1.0 mEq daily. Two sham-operated groups with intact kidneys also were studied. Group 3 consumed 1.7 +/- 0.2 mEq daily and group 4 ate 15.2 +/- 1.4 mEq daily. These levels of intake were designed to provide at least as much potassium per liter of GFR in the sham groups as in the remnant kidney rats. Systolic BP (SBP), 24-h protein excretion, plasma aldosterone levels, 24-h urinary aldosterone excretion, and plasma renin activity (PRA) were determined in all groups at 2 wk. At 4 wk, after SBP and protein excretion measurements, remnant kidneys were perfusion-fixed for morphometric analysis. SBP was normal in both sham-operated groups and was not different between the groups (113 +/- 13 versus 117 +/- 2 mmHg, group 3 versus group 4). In the remnant animals, SBP at 2 wk followed potassium intake: Group 1 had a lower SBP than group 2 (140 +/- 26 versus 170 +/- 34 mmHg, P = 0.005). The same SBP pattern persisted at 4 wk (153 +/- 25 versus 197 +/- 27 mmHg, group 1 versus group 2, P = 0.0006). However, 24-h urinary protein excretion was not different between the two groups with remnant kidneys at either 2 or 4 wk. Both plasma and 24-h urinary aldosterone excretion at 2 wk followed potassium intake (120 +/- 124 versus 580 +/- 442 pg/ml for plasma aldosterone, group 1 versus group 2, P = 0.03, and 2.6 +/- 1.8 versus 23.2 +/-9.8 ng/d for urinary aldosterone, group 1 versus group 2, P = 0.0001). PRA, however, followed a reverse pattern in which dietary potassium restriction resulted in higher levels (16 +/- 6 versus 6 +/- 3 ng angiotensin I/ml per h, group 1 versus group 2, P = 0.01). A similar pattern for PRA and aldosterone excretion was also observed in the sham groups, in which lower potassium intake also resulted in a significantly higher PRA and lower aldosterone excretion. The constancy of BP in the sham groups likely reflects their lack of nephron reduction and greater sodium excretory capacity. Morphometric analysis in remnant animals revealed no significant difference between the two dietary groups in the prevalence of glomerular sclerosis, glomerular volume, or interstitial volume. It is concluded that dietary potassium is a potent determinant of hypertension in the remnant kidney model probably through the actions of aldosterone and that the high aldosterone secretion in this model is a function of the dietary potassium load. In this model, reduction in nephron number is also critical in promoting hypertension in conjunction with hyperaldosteronism.     

No involvement of antidiuretic hormone in acute antidiuresis during PEEP ventilation in humans

Decreased urinary output (Vu ml/min) after institution of PEEP is attributed to a variety of mechanisms including decreased cardiac output and renal blood flow (RBF), activation of neurohormonal reflexes, increased catecholamines, plasma renin activity (PRA), and antidiuretic hormone (ADH) release. To evaluate these factors, seven normovolemic patients (36 yr +/- 13 SD), free of preexisting lung, cardiac, or renal disease, requiring continuous mandatory ventilation for neurologic reasons were studied. The authors measured or calculated: total blood volume (TBV) (51Cr); right atrial, pulmonary arterial, pulmonary wedge, and systemic pressures, cardiac index (CI); renal plasma flow (RPF) (iodohippurate sodium 131I [131I PAH] clearance); glomerular filtration rate (GFR) (creatinine clearance), free water clearance (CH2O), osmolal clearance (Cosm), fractional excretion of sodium (FENa+) and potassium (FEK+); and plasma renin activity (PRA) (ng X ml-1 X h-1), plasma ADH (pg/ml; radioimmunoassay), epinephrine (E in pg/ml), and norepinephrine (NE in pg/ml) (double-isotope radioenzymatic assay). Two conditions were studied after 90-min steady state: 1) zero PEEP (ZEEP); and 2) 15 cmH2O PEEP. PEEP caused a significant decrease in CI (-21%; P less than 0.01) and RPF (-19%; P less than 0.05) without significant decrease in GFR. A significant decrease in Vu (-55%; P less than 0.05), FENa+ (-39%; P less than 0.05) and Cosm (-36%; P less than 0.25) occurred without modification in CH2O. Plasma ADH remained in the normal range and did not increase when PEEP was applied.(ABSTRACT TRUNCATED AT 250 WORDS)     

Observations on the activity of the renin-angiotensin-aldosterone (RAA) system after low volume colloid resuscitation for burn injury

Studies of plasma renin activity (PRA) and plasma aldosterone in burn patients treated with a low volume colloid resuscitation regimen revealed very high levels of both hormones. Highest hormone levels occurred in the 5 days post burn with the correlation between PRA and plasma aldosterone r = +0.787 (p less than 0.001). The negative correlation between 24 hour urinary sodium excretion and PRA (r = +0.671, p less than 0.001), was closer than that between 24 hour sodium excretion and plasma aldosterone (r = -0.556, p less than 0.01). Secondary elevations of PRA and plasma aldosterone occurred in 2 patients (7-14 days after injury) associated with clinical deterioration and systemic sepsis.     

Atrial natriuretic peptide and other vasoactive hormones in nephrotic syndrome

Plasma levels of atrial natriuretic peptide (ANP), arginine vasopressin (AVP), renin activity (PRA), aldosterone (PA), catecholamines and urinary prostaglandins (PG), as well as renal function were measured in children in the edematous state of the nephrotic syndrome before and after infusion of human serum albumin. Before albumin infusion, plasma levels of AVP, PRA, PA and noradrenaline (NA) and urinary excretion of PGE2, PGE-Met, PGF2 alpha were elevated. The mean value of plasma ANP was in the normal range. Albumin infusion produced a 36% increase in the calculated plasma volume. It was associated with a fivefold rise in the plasma level of ANP (31.6 +/- 22.6 vs. 151.4 +/- 52 fmol/ml mean, SD), and a significant fall in the levels of PRA, AVP, PA, and NA. Similarly, urinary concentration of PGE2, PGE-Met and PGF2 alpha fell. Urine flow, GFR, UNaV, FENa, and COsm increased significantly, while CH2O remained unchanged. The diuresis, natriuresis and GFR correlated with the level of plasma ANP, while urinary sodium excretion did not correlate with PA or NA levels. These findings suggest that ANP plays an important role in albumin induced natriuresis in children with nephrotic syndrome.     

Renal hemodynamics, urinary eicosanoids, and endothelin after liver transplantation.

Patients with hepatic cirrhosis develop widespread abnormalities in kidney function and vasoactive hormones. These change rapidly after liver transplantation during immunosuppression with cyclosporine. The role of changing eicosanoid excretion and endothelin levels in regulating renal function after transplantation in humans remains uncertain. We studied 32 patients with regard to renal hemodynamics, glomerular filtration, urinary prostacyclin (6-keto-PG-F1-alpha), thromboxane (TBX2), and endothelin before and during the first four weeks after orthotopic liver transplantation. Arterial pressure rose from 106 +/- 2/61 +/- 2 to 146 +/- 4/81 +/- 2 mmHg, (P less than .001), while renal blood flow fell (686 +/- 38 to 453 +/- 24 ml/min/1.73 m2, P less than .05), as did GFR. Pretransplant excretion of 6-keto and TBX2 was above that of normal subjects and fell progressively after transplant, as did plasma renin activity and aldosterone. The 6-keto levels fell below normal after two weeks. The ratio of TBX2/6-keto remained elevated compared with normal subjects throughout the month after transplant (1.54 +/- 0.38 vs. 0.54 +/- 0.07, P less than .01). Endothelin levels rose during the first week (7.4 +/- 1.4 vs. 12.4 +/- 2.7 pg/ml, P less than .05), but fell back to baseline thereafter. These results indicate that high levels of urinary eicosanoids in patients with liver disease fall rapidly after liver transplantation during CsA immunosuppression. Unlike results in many experimental models, these data suggest that renal vasoconstriction in humans may be associated primarily with suppression in renal prostacyclin excretion rather than stimulation of thromboxane.     

Doses of endothelin have natriuretic effects in conscious rats with cirrhosis and ascites

MAP, RPF, GFR, V and UNaV were measured in nine conscious control and in 11 conscious cirrhotic rats with ascites before and following two bolus injections (100 and 600 pmol/kg body wt) of endothelin (ET). PRA and plasma concentration of aldosterone and ANP were measured in basal conditions and following the high dose ET. ET induced similar increase in MAP and decrease in RPF and GFR in control and cirrhotic rats. High-dose ET produced a significant reduction in UNaV in control rats (from 2.22 +/- 0.46 to 1.14 +/- 0.28 microEq/min, P less than 0.01). By contrast, it induced marked natriuresis in cirrhotic rats (from 0.76 +/- 0.18 to 2.31 +/- 0.70 microEq/min, P less than 0.05). ET significantly increased aldosterone (control rats: 59.3 +/- 2.2 vs. 85.4 +/- 7.4 ng/dl, P less than 0.025; cirrhotic rats: 115.0 +/- 15.8 vs. 163.9 +/- 30.8, ng/dl, P less than 0.05) and ANP (control rats: 20.1 +/- 3.4 vs. 42.7 +/- 7.7, fmol/ml, P less than 0.025; cirrhotic rats: 107.5 +/- 17.3 vs. 214.2 +/- 41.1, fmol/ml, P less than 0.025) and significantly suppressed PRA (control rats: 2.5 +/- 0.5 vs. 0.2 +/- 0.04, ng/ml.hr, P less than 0.025; cirrhotic rats: 16.6 +/- 2.9 vs. 5.0 +/- 1.1, ng/ml.hr, P less than 0.01) in both groups of animals. These results indicate that ET has marked natriuretic properties in cirrhosis with ascites due to inhibition of tubular sodium reabsorption.     

Elevation of plasma endothelin associated with systemic hypertension in humans following orthotopic liver transplantation.

Endothelin (ET) is a 21-amino-acid peptide of endothelial origin, is a potent systemic and renal vasoconstrictor associated with sodium retention and modulation of the renin-angiotensin-aldosterone system. The present study was designed to determine if plasma ET is elevated in humans with cirrhosis (n = 12), a state characterized by sodium retention and increased plasma renin activity (PRA) and plasma aldosterone (PA), and to determine the effect of orthotopic liver transplantation (OLT) upon plasma ET, PRA, and PA at 1, 3, and 7 days after transplantation. Plasma ET before OLT was 1.62 +/- 0.23 pg/ml, which was not different as compared with normal controls. Plasma ET significantly increased to 4.18 +/- 0.66, 3.87 +/- 0.58, and 4.07 +/- 0.61 pg/ml, respectively following OLT. PRA remained elevated throughout the postoperative course, in contrast to PA that decreased following OLT. Mean arterial pressure increased significantly from 82 +/- 4 pre-OLT to 98 +/- 4 and 103 +/- 2 mmHG on days 3 and 7 respectively.     

Arterial blood pressure and the renin-angiotensin-aldosterone system during postural changes in hypertensive patients with unilateral renal mobility

Unilateral renal mobility was identified in 27 out of 100 essential hypertensive patients by examination of renal scintiphotos. The pattern of response to postural changes of blood pressure (BP), plasma renin activity (PRA) and plasma aldosterone concentration (PAC) was investigated in 11 patients with renal mobility and without treatment and compared with that of an age- and sex-matched group of untreated hypertensives without renal mobility. The patients with renal mobility had higher BP levels (X +/- SD mm Hg: supine 185 +/- 39/112 +/- 18 vs. 149 +/- 18/97 +/- 14; upright 167 +/- 38/108 +/- 17 vs. 144 +/- 7/93 +/- 10; p less than 0.05). Significant correlations were obtained in the patients with renal mobility (but not in those without renal mobility) between upright PRA and PAC (p less than 0.001), their postural variations (p less than 0.01) and between upright PRA (and PAC) and BP levels (p less than 0.05). The high prevalence of renal mobility in hypertension and the relationship observed between the activated renin-angiotensin-aldosterone system and BP in this condition suggest the importance of searching for unilateral renal mobility when examining the renin-angiotensin-aldosterone system in hypertensive patients, particularly during postural manoeuvres.     

Reduced angiotensin receptors and pressor responses in hypotensive hemodialysis patients

A sub-set of patients on chronic hemodialysis develop sustained hypotension (systolic pressure less than 100 mm Hg). To determine whether this hypotension could be due to altered production of, or sensitivity to angiotensin II (AII), we measured plasma renin (PRA), AII, and aldosterone in nine hypotensive and nine normotensive dialysis patients; we also assessed their sensitivity to infused AII and studied AII binding to their platelets as an indicator of AII receptors on vascular smooth muscle. All studies were performed just before dialysis when subjects were relatively volume-expanded. Hypotensives had higher PRA (5.7 +/- 2.4 vs. 2.1 +/- 0.8 ng AI/ml/hr, P less than 0.05). AII (56 +/- 15 vs. 31 +/- 3 pg/ml), and aldosterone (91 +/- 35 vs. 21 +/- 7 ng/dl, P less than 0.05) than did normotensives. During AII infusion at 1, 3, 10, and 30 ng/kg/min for 15 minutes each, hypotensives displayed a significantly blunted pressor effect across the range of AII doses. In parallel with this, hypotensives showed reduced AII receptors on their platelets compared to normotensives (0.8 +/- 0.4 vs. 3.6 +/- 1.0% 125I-AII specifically bound; P less than 0.03). Binding analysis revealed a single affinity state for the AII receptors which was similar in both groups (Kd = 3.2 +/- 1.1 for hypotensives vs. 3.8 +/- 0.7 x 10(-10) M for normotensives). The two groups had similar levels of plasma catecholamines, similar slowing of heart rate during AII infusion and no postural hypotension, indicating intact sympathetic nervous system pathways.(ABSTRACT TRUNCATED AT 250 WORDS)     

Insulin action in obese non-insulin-dependent diabetics and in their isolated adipocytes before and after weight loss

To determine the effects of weight loss on insulin action in patients with non-insulin-dependent diabetes mellitus (NIDDM) and in their isolated adipocytes, we studied nine weight-stabilized Pima Indians [7 females and 2 males; age 39 +/- 3 yr; wt 99.9 +/- 8.2 kg; body fat 39 +/- 2% (means +/- SE)] before and after a 6.7 +/- 1.3-kg weight loss and decrease in fasting plasma glucose from 250 +/- 11 to 148 +/- 15 mg/dl. In vivo insulin action was measured during a 3-insulin-step, hyperglycemic (approximately 310 mg/dl) clamp with somatostatin (250 micrograms/h). At a clamp plasma insulin concentration of 10 microU/ml, glucose disposal rates did not change after weight loss; at approximately 100 microU/ml, glucose disposal rates increased by 21% [from 4.3 +/- 0.2 to 5.3 +/- 0.4 mg X min-1 X kg-1 of fat-free mass (FFM), P less than .01] mostly due to increased carbohydrate oxidation rates (2.0 +/- 0.3 to 2.8 +/- 0.3 mg X min-1 X kg-1 FFM, P less than .02); at 2400 microU/ml, glucose disposal rates increased by 37% (11.4 +/- 0.6 to 15.6 +/- 1.4 mg X min-1 X kg-1 FFM, P less than .02) mostly due to increased nonoxidative carbohydrate disposal rates or storage (7.5 +/- 0.6 to 10.9 +/- 1.3 mg X min-1 X kg-1 FFM, P less than .04). Sensitivity of glucose disposal to insulin in the physiologic range (measured as change in glucose disposal rate per unit change in insulin concentration between clamps at approximately 10 and approximately 100 microU/ml) was very low in these diabetic subjects and did not change after weight loss. Adipocyte cell size, basal and maximal insulin-stimulated glucose transport, and half-maximal rate for transport did not change after weight loss. The data suggest that insulin in the physiologic range has no apparent effect on glucose disposal in patients with NIDDM before or after weight loss. However, a moderate weight loss is associated with enhanced capacity to transport and metabolize glucose in vivo. The discrepancy between in vivo and in vitro results suggests that the adipocyte may not always reflect in vivo insulin action. Diabetes 36:227-36, 1987.     

Plasma palmitate turnover in subjects with thermal injury

Using a continuous infusion of [1-13C] palmitic acid tracer, plasma palmitate turnover was measured 14 times in nine bandaged, thermally injured adults. Plasma glucose (102 +/- 4 mg/dl), insulin (21 +/- 4 microU/ml), and glucagon (296 +/- 34 pg/ml) levels were significantly elevated compared with values in uninjured controls. Circulating plasma epinephrine (67 +/- 11 pg/ml) and norepinephrine (219 +/- 57 pg/ml) levels were more than twofold their respective control values of 261 +/- 4 pg/ml and 211 +/- 7 pg/ml but less than the previously defined plasma threshold levels for lipolytic effects of these catecholamines as circulating hormones. Plasma palmitate and free fatty acid concentrations, 113 +/- 8 and 452 +/- 38 microM, respectively, were not different from control values but palmitate flux (2.66 +/- 0.28 mumol kg-1 min-1) and free fatty acid turnover calculated therefrom (10.53 +/- 1.13 mumol kg-1 min-1) were significantly elevated compared to the control rates. While palmitate turnover significantly correlated with plasma palmitate concentration and with per cent body surface area burned, there was no relationship between palmitate flux and circulating epinephrine or norepinephrine levels. These data raise new questions about the relative catabolic roles of catecholamines in bandaged, thermally-injured patients.     

Effect of demeclocycline on renal function and urinary prostaglandin E2 and kallikrein in hyponatremic cirrhotics

8 cirrhotics with hyponatremia were given demeclocycline (DMC) 900 mg/day to investigate its effect on renal function, plasma renin activity, aldosterone and urinary excretion of prostaglandin E2 and kallikrein. In 7 patients DMC induced an increase of free water clearance (from -0.36 +/- 0.06 to 0.13 +/- 0.06 ml/min) and serum sodium concentration (from 125.4 +/- 0.09 to 131.1 +/- 1.0 mEq/l, mmol/l). In 5 of these patients DMC also induced a marked reduction of glomerular filtration rate (from 72.2 +/- 6.2 to 31,2 +/- 4.7 ml/min) and renal plasma flow (from 468 +/- 98 to 195 +/- 55 ml/min) which could not be explained on the basis of hypovolemia. In each case this renal impairment was not associated with changes in urinary concentration of beta 2-microglobulin, urinary casts excretion, fresh urine sediment or urine protein content and disappeared after discontinuation of the drug. DMC induced a marked increase in the urinary excretion of prostaglandin E2 (from 0.82 +/- 0.27 to 6.16 +/- 1.91 ng/min) in 6 out of the 7 patients who responded to DMC and a marked reduction in urinary kallikrein (from 16.1 +/- 4.4 to 4.2 +/- 1.6 pkat/min) in the 5 patients who developed renal insufficiency. The serum DMC concentration was greater than 5 micrograms/ml in all patients who responded to DMC, greater than 8 micrograms/ml in all cases who developed renal insufficiency and of 3 micrograms/ml in the case not responding to DMC. (ABSTRACT TRUNCATED AT 250 WORDS)     

Atrial natriuretic factor in the acute nephritic and nephrotic syndromes

Because the role of systemic hormones in the pathophysiology of edema in acute renal disease remains incompletely understood, we compared the levels of atrial natriuretic factor (ANF) and plasma renin activity (PRA) in patients with acute glomerulonephritis (AGN), nephrotic syndrome (NS), and normal individuals during salt deprivation and salt loading. Sixteen patients with AGN (10 males) and nine patients with NS and hypoalbuminemia (7 males) were studied on admission, and after recovery (12 AGN patients) or remission (4 NS patients). Eighteen normal controls were each studied after five days on a low (20 mEq Na/day), regular (120 mEq Na/day) and high (300 mEq Na/day) dietary salt intake. Patients with AGN and NS had comparable edema (AGN 2.8 +/- 0.53 kg; NS 3.36 +/- 0.47 kg; SE) and urinary Na excretion (mean +/- SEM: AGN 0.97 +/- 0.11 mEq/hr; NS 1.06 +/- 0.16 mEq/hr), but AGN patients had five times higher ANF (AGN 27.2 +/- 4.06 fmol/ml; NS 5.51 +/- 1.02 fmol/ml; P less than 0.001) and six times lower PRA ng/liter.sec levels (AGN 0.187 +/- 0.047; NS 1.144 +/- 0.222; P less than 0.001) than NS patients. The degree of edema was correlated with ANF levels in AGN patients (P less than 0.001) but not in NS patients. There was a strong exponential negative correlation (r = -0.773, P less than 0.0001) between ANF and PRA, in which AGN patients and Na-restricted controls were located in the opposite ends of the volume sensing-response, and NS patients in the middle, alongside controls with regular Na intake.(ABSTRACT TRUNCATED AT 250 WORDS)     

Renal tubular function in cirrhotic patients with ascites: special reference to lithium clearance following the human atrial natriuretic peptide administration]

Synthetic alpha-human atrial natriuretic peptide (alpha-hANP), 1 micrograms/kg, was intravenously given to 16 cirrhotic patients with ascites and 9 control subjects (CS) to investigate major factors responsible for sodium retention and refractory ascites. The following parameters were measured before and after alpha-hANP administration; such as lithium clearance (CLi) as an index of fluid delivery to the distal tuble, mean arterial pressure (MAP), urinary sodium excretion rate (UNaV), urine volume (V), glomerular filtration rate (GFR), effective renal plasma flow (ERPF), plasma renin activity (PRA), plasma aldosterone concentration (PAC), urinary excretion of prostaglandin (PG)E2, 6-keto-PGF1 alpha (6-k-PGF1 alpha), and thromboxane B2 (TxB2). Patients were divided following alpha-hANP administration into 2 groups as "good responders (GR)" and "poor responders (PR)", in which GR was defined as the group showing 2-fold-increase in UNaV. In contrast, PR had significant lower MAP (71.8 +/- 5.04 mmHg), GFR (21.3 +/- 3.90 ml/min), ERPF (158.0 +/- 43.8 ml/min), FELi (CLi/GFR; 12.6 +/- 1.26%), and higher PRA (8.72 +/- 0.99 ng/ml/h) and PAC (12.2 +/- 3.13 ng/dl) than GR. GR demonstrated almost same natriuretic response as CS with an increase of GFR and renal PGs synthesis, and a decrease of FELi despite reduction in blood pressure. However, alpha-hANP did not suppress PRA, PAC, and distal tubular reabsorption of sodium (FDRNa = 1-FENa/FELi) in cirrhotic patients, whereas suppressed in CS. UNaV correlated with FELi (r = 0.687, p = 0.01) and GFR (r = 0.777, p = 0.01). PRA correlated with FELi r = 0.669, p = 0.015), GFR (r = -0.634, p = 0.018), and MAP (r = 0.858, p = 0.001) only in cirrhosis. These results therefore indicated that hypotension caused by hemodynamic alteration and extremely stimulated renin release might effect on proximal tubular sodium reabsorption and GFR, leading to sodium retention and diuretic resistance in cirrhosis.