Failure of atrial natriuretic factor to increase with saline load in patients with dilated cardiomyopathy and mild heart failure.

To investigate whether the response of atrial natriuretic factor (ANF) to volume expansion is impaired in the early stages of dilated cardiomyopathy, the effects of saline load (SL; 0.25 ml/kg.min for 120 min) were assessed in 12 patients with dilated cardiomyopathy and asymptomatic to mildly symptomatic heart failure (HF) and in nine normal subjects (N). SL increased plasma ANF levels in N (from 14.3 +/- 2 to 19.5 +/- 3 and 26 +/- 4 pg/ml, at 60 and 120 min, respectively, P less than 0.001), but not in HF (from 42.9 +/- 9 to 45.9 +/- 9 and 43.9 +/- 8 pg/ml). Left ventricular end-diastolic volume (LVEDV) and stroke volume were increased (P less than 0.001) by SL in N but not in HF. Urinary sodium excretion (UNaV) increased in N more than in HF during SL, whereas forearm vascular resistance (FVR) did not change in N and increased in HF (P less than 0.001). In five HF patients SL was performed during ANF infusion (50 ng/kg, 5 ng/kg.min) that increased ANF levels from 37.1 +/- 10 to 146 +/- 22 pg/ml. In this group, SL raised both LVEDV (P less than 0.01) and ANF (P less than 0.05), whereas FVR did not rise. In addition, the UNaV increase and renin and aldosterone suppressions by SL were more marked than those observed in HF under control conditions. Thus, in patients with dilated cardiomyopathy and mild cardiac dysfunction, plasma ANF levels are not increased by volume expansion as observed in N. The lack of ANF response is related to the impaired cardiac adaptations. The absence of an adequate increase of ANF levels may contribute to the abnormal responses of HF patients to saline load.     

What stimulates atrial natriuretic factor release during exercise?

Prior studies have shown that circulating atrial natriuretic factor (ANF) increases during short-term exercise, but the mechanism controlling ANF release, as well as the effect of exercise training on ANF release, remains unclear. Fifteen healthy mongrel dogs underwent short-term exercise testing before and after a 12-week period of exercise training (n = 8) or cage confinement (n = 7). ANF, norepinephrine, epinephrine, right atrial pressure, and heart rate were measured simultaneously at rest and during exercise at the time of each acute exercise study. Data were analyzed for all animals with normal baseline ANF values. Exercise training had no modulating effect on circulating ANF levels at rest or during exercise. Therefore, data before and after exercise training or cage confinement were grouped (n = 24) to determine the effects of short-term exercise. ANF levels increased from 49 +/- 2 pg/ml at rest to 60 +/- 4 pg/ml during exercise (p less than 0.05). Heart rate, norepinephrine, and epinephrine values also increased, but right atrial pressure actually decreased from 2.3 +/- 0.9 mm Hg at rest to -3.8 +/- 0.9 mm Hg during exercise (p less than 0.05). There was no correlation between ANF concentrations and levels of these other variables either at rest of during exercise. By demonstrating an increase in ANF with a simultaneous decrease in right atrial pressure, this study clearly shows that increased right atrial pressure is not the secretory stimulus for ANF release during exercise in the normal dog. The lack of correlation between ANF and right atrial pressure, heart rate, norepinephrine, and epinephrine levels suggests that factors other than these variables stimulate ANF release during short-term exercise.     

Effect of Different AV Delays on Left Ventricular Diastolic Function and ANF Levels in DDD Paced Hypertensive Patients During Daily Activity and Exercise

Fifteen hypertensive patients (13 men) with left ventricular hypertrophy, mean age 69 6 5 years, having complete heart block and paced in the DDD mode, were studied by two-dimensional and Doppler echo in 100 and 200 ms atrioventricular delays. ANF plasma levels were measured at rest and at peak exercise, during pacing with the two different atrioventricular delays. ANF plasma levels were significantly higher at pacing with long atrioventricular delays (200 ms), at rest (152.47 6 12.38 pg/mL vs 119 6 12.38 pg/mL, P, 0.001) and at exercise (180.93 6 11.51 vs 123.67 6 16.24 pg/mL, P, 0.0001). ANF plasma levels were significantly increased at exercise, compared to those at rest during pacing with the two different atrioventricular delays, but we found a more pronounced increase of ANF levels (from 152.47 6 10.49 pg/mL to 180.93 6 11.51 pg/mL), when the atrioventricular delays was set to 200 ms (P, 0.0001). A significant decrease of isovolumic relaxation time (from 123.33 6 20.5 to 105.33 6 11.06 ms, P, 0.001) was observed, during pacing with the short atrioventricular delays. Moreover, the peak early (E) to peak atrial (A) velocity ratio (E/A) was declined (from 0.89 6 0.7 to 0.57 6 0.18, P, 0.05). We also noticed that patients with small left ventricles exhibit greater increase in ANF plasma levels during DDD pacing with long atrioventricular delays (r 5 20.792, P 5 0.000). In conclusion, left ventricular diastolic function of our patients seems to be improved during DDD pacing with short (100 ms) atrioventricular delays, as it was expressed by echocardiographic and hormonal measurements.     

lnterleukin-8 and neutrophil activation in acute pancreatitis

It has been suggested that leucocytes play an important role in the pathogenesis of complicated pancreatitis. Indeed, increased plasma concentrations of neutrophil elastase as a marker of neutrophil activation could be detected in patients with a severe course of the disease. Recently, interleukin-8 (IL-8) has been described as a novel neutrophil activating peptide. To determine the role of IL-8 in acute pancreatitis we measured its serum concentrations by a specific enzyme-linked immunosorbent assay in 10 patients with acute pancreatitis daily during the first week of hospitalization. IL-8 levels were compared with plasma concentrations of neutrophil elastase and the clinical course of the disease. Three of the patients had uncomplicated pancreatitis, while seven showed various extrapancreatic complications. Patients with complicated pancreatitis had statistically significant (P less than 0.05) higher mean values of IL-8 (121 +/- 41 pg/ml-1 vs. 13 +/- 6 pg ml-1, mean +/- SEM) and neutrophil elastase (547 +/- 35 ng ml-1 vs. 250 +/- 20 ng ml-1) than patients with uncomplicated disease. There was a positive correlation (r = 0.52, P less than 0.0001) between IL-8 and neutrophil elastase in the lower concentration range of IL-8 (less than 100 pg ml-1). At IL-8 levels greater than 100 pg ml-1 neutrophil elastase was always greatly elevated; however, under these conditions the relationship between IL-8 and elastase was no longer linear. No measurable IL-8 concentrations were found when plasma elastase was less than 200 ng ml-1. During follow-up, initially elevated IL-8 concentrations decreased in correlation with clinical improvement.(ABSTRACT TRUNCATED AT 250 WORDS)     

Changes in plasma renin activity and haemodynamics during vasodilator therapy in conscious dogs with myocardial infarction or chronic volume overload

The aim of the study was to compare the changes in plasma renin activity induced by a vasodilator in normal dogs and in dogs with an impaired cardiac reserve. In normal conscious dogs, a 60-min nitroprusside infusion increased plasma renin activity from 1.05 +/- 0.26 to 8.35 +/- 1.20 ng, angiotensin I ml-1 h-1 (P less than 0.002) and heart rate from 83 +/- 6 to 149 +/- 15 beats/min (P less than 0.002). In five dogs in which a aortocaval fistula had been created 4 weeks earlier, the same infusion still increased plasma renin activity but significantly less than in normal dogs (0.90 +/- 0.29 to 4.44 +/- 0.64 ng ml-1 h-1; P less than 0.01) and the heart rate was unchanged (134 +/- 4 to 139 +/- 7 beats/min; NS). Similarly, in five dogs with a previous myocardial infarction, the heart rats response to nitroprusside was blunted (108 to 107 beats/min;NS) and plasma renin activity increased less than in normal dogs. Plasma renin activity also increased acutely after hydralazine administration in dogs which myocardial infarction (1.05 +/- 0.26 to 8.99 +/- 0.79 ng ml-1 h-1; P less than 0.05); after 1 week of hydralazine, plasma volume had increased from 54.9 +/- 0.9 ml kg-1 to 74.5 +/- 4.9 ml kg-1 (P less than 0.05) and plasma renin activity remained higher than control (4.66 +/- 0.66 ng ml-1 h-1; P less than 0.01). In conclusion, vasodilator therapy rapidly activates vasoconstrictor forces and fluid retention even in dogs with limited cardiac reserve. Although the regulation of plasma renin secretion appears altered in these models of heart disease, the renin response remains sufficient to seriously limit the beneficial effects of vasodilator therapy.     

Sequential changes in atrial pressures, dimensions, and plasma atrial natriuretic factor concentrations during volume loading in hemodynamically normal human subjects.

The effects of volume loading on atrial pressures and dimensions, plasma levels of atrial natriuretic factor (ANF), and other neurohormonal variables were studied in 11 patients with normal hemodynamics with the patients in a supine -15 degree left decubitus posture by infusing 750 ml of normal saline solution over 30 minutes. Right and left atrial areas were measured by two-dimensional echocardiography. Plasma ANF level was sampled simultaneously from the pulmonary artery, aorta, and femoral artery and vein. At 30 minutes into the infusion, pulmonary capillary wedge pressure and right atrial pressure increased from 5.6 +/- 2.8 mm Hg (mean +/- SD) and 6.4 +/- 2.2 mm Hg to 10.2 +/- 3.2 and 9.5 +/- 2.2 mm Hg, respectively (both p less than 0.01). Left atrial area increased from 12.6 +/- 2.2 cm2 to 15.0 +/- 2.1 cm2 (p less than 0.05), whereas right atrial area did not change. Plasma ANF levels from all sampling sites increased significantly (e.g., 43 +/- 21 pg/ml to 71 +/- 62 pg/ml in the femoral artery, p less than 0.05). Plasma norepinephrine and renin levels were unchanged, whereas aldosterone level declined significantly. At 30 minutes after termination of the infusion, atrial pressures declined to baseline values in all patients. However, left atrial area remained significantly increased, and a trend for systemic arterial plasma ANF level to remain increased was seen. Plasma aldosterone level remained significantly suppressed.(ABSTRACT TRUNCATED AT 250 WORDS)     

Atrial natriuretic factor in chronic obstructive lung disease with pulmonary hypertension. Physiological correlates and response to peptide infusion.

To investigate the physiological role of atrial natriuretic factor (ANF) in patients with hypoxic pulmonary hypertension secondary to chronic obstructive lung disease (COLD), we infused synthetic alpha-human ANF in seven such patients, and investigated the physiological correlates to circulating peptide levels in 24 patients with COLD. ANF infusion, at incremental rates of 0.01, 0.03, and 0.1 micrograms/kg.min, increased basal plasma immunoreactive (ir) ANF (136 +/- 38 pg/ml) by 3-, 10-, and 26-fold, respectively, and reduced pulmonary artery pressure (from 33 +/- 3 to 25 +/- 2 mmHg, P less than 0.001) and systemic arterial pressure (from 88 +/- 4 to 79 +/- 4 mmHg, P less than 0.001) in a dose-related fashion. Cardiac index increased by 13.5% (P less than 0.01) while heart rate was unchanged. Cardiac filling pressures decreased at 0.1 micrograms/kg.min ANF. Pulmonary and systemic vascular resistance fell by 37% (P less than 0.001) and 19% (P less than 0.001), respectively. Arterial oxygenation was impaired during ANF infusion, suggesting partial reversal of hypoxic pulmonary vasoconstriction. Plasma renin activity remained unchanged but aldosterone fell by 44% (P less than 0.01). The levels of plasma irANF in 24 patients correlated directly with the degree of hemoconcentration (r = 0.67, P less than 0.001), respiratory acidosis (r = -0.65, P less than 0.001), and pulmonary hypertension (r = 0.52, P less than 0.01). The results suggest that ANF may serve as a potent pulmonary vasodilator involved in the circulatory homeostasis of patients with COLD.     

Atrial natriuretic factor: comparability of venous and arterial plasma measurements in man at rest and during exercise

1. Simultaneously obtained arterial and venous plasma atrial natriuretic factor (ANF) concentrations were compared at supine rest and during graded dynamic leg exercise in 10 healthy male subjects (aged 33-51 years). 2. Arterial ANF concentrations ranged between 12 and 179 pg/ml and venous concentrations between 9 and 177 pg/ml. 3. A positive correlation between arterial and venous concentrations was found (r = 0.984). 4. Arterial ANF concentrations were higher than venous concentrations in all pairs of samples (n = 31), but the difference was small and changed little with exercise: the mean difference was 5 pg/ml at rest, 12 pg/ml during submaximal exercise and 6 pg/ml during maximal exercise. 5. The extraction ratios for ANF varied greatly, but were in general lower (P less than 0.05) during maximal exercise (median 0.07, range 0.01-0.32) than at rest (median 0.22, range 0.05-0.33). 6. It was concluded that the plasma ANF concentration in a peripheral arm vein is a good indicator of the systemic peptide concentration at rest as well as during dynamic leg exercise.     

Role of atrial natriuretic factor, cyclic GMP and the renin–aldosterone system in acute volume regulation of healthy human subjects

The role of the atrial natriuretic factor (ANF), its second messenger cyclic guanosine monophosphate (cGMP), and the counteracting renin-aldosterone system in acute volume regulation was investigated in 25 healthy human subjects. Central volume stimulation by 1-h head-out water immersion (WI) into a thermoneutral water-bath increased plasma levels of ANF (mean +/- SEM) from 6.0 +/- 0.6 to 13.6 +/- 2.6 fmol ml-1. This was paralleled by a rise of plasma cGMP levels from 1.9 +/- 0.2 to 2.8 +/- 0.4 pmol ml-1, and an increase of urinary cGMP excretion from 340 +/- 64 to 692 +/- 103 pmol min-1. Water immersion reduced plasma aldosterone concentration (PAC) from 13.0 +/- 1.7 to 6.5 +/- 0.8 ng 100 ml-1 and plasma renin activity (PRA) from 5.3 +/- 0.9 to 2.4 +/- 0.3 ng AI ml-1 h-1. Volume stimulation markedly increased diuresis and natriuresis. Whereas the plasma cGMP increase correlated with plasma ANF stimulation, neither ANF nor PRA or PAC correlated with basal or stimulated renal parameters. Water immersion-induced changes in natriuresis and urinary cGMP excretion were correlated. These data suggest a role of ANF and cGMP in acute volume regulation of healthy human subjects.     

Evidence that calcitonin stimulates 1,25-dihydroxyvitamin D production and intestinal absorption of calcium in vivo.

Although it is well established that parathyroid hormone and phosphate are important regulators of 1,25-dihydroxyvitamin D [1,25(OH)2D] production, it remains unclear whether calcitonin affects vitamin D metabolism in vivo. Experiments were performed in the rat to determine the effect of chronic calcitonin infusion (0.2 U X h-1) on plasma levels of vitamin D metabolites and on calcium metabolism. Thyroparathyroidectomized animals fed a calcium-replete or calcium-free diet were studied for as long as 2 wk before they were killed. In control rats, a calcium-free diet alone for 12 d resulted in an increase in 1,25(OH)2D levels from 24 +/- 5 to 139 +/- 37 pg . ml-1, P = 0.025. The infusion of calcitonin also stimulated 1,25(OH)2D levels compared with controls on a regular diet (80 +/- 17 vs. 38 +/- 6 pg . ml-1, P less than 0.05) and on a calcium-free diet (460 +/- 50 vs. 139 +/- 37 pg . ml-1, P less than 0.001). In addition, calcitonin increased plasma calcium levels in animals on a regular diet by 50%; this effect was most likely due to increased intestinal absorption of calcium, because removal of calcium from the diet markedly blunted this effect. In contrast, calcitonin administration did not significantly affect 25(OH)D plasma levels. Collectively, these data suggest that calcitonin and calcium are independent regulators of 1,25(OH)2D production and that calcitonin stimulates intestinal absorption of calcium, by increasing circulating levels of 1,25(OH)2D.     

Normal human left and right ventricular and left atrial dimensions using steady state free precession magnetic resonance imaging.

PURPOSE: The aim of this project was to establish a database of left and right ventricular and left atrial dimensions in healthy volunteers using steady-state free precession cardiac magnetic resonance imaging, the clinical technique of choice, across a wide age range. METHODS: 108 healthy volunteers (63 male, 45 female) underwent cardiac magnetic resonance imaging using steady-state free precession sequences. Manual analysis was performed by 2 experienced observers. RESULTS: Left and right ventricular volumes and left ventricular mass were larger in males than females: LV end-diastolic volume 160 +/- 29 mL vs. 135 +/- 26 mL, LV end-systolic volume 50 +/- 16 mL vs. 42 +/- 12 mL; RV end-diastolic volume 190 +/- 33 mL vs. 148 +/- 35 mL, RV end-systolic volume 78 +/- 20 mL vs. 56 +/- 18 mL (p < .05 for all). Normalization of values to body surface area removed the statistical differences for LV volumes, but not for LV mass or RV volumes. With increased age, males showed a significant decrease in volume and mass indices for both ventricles, while female values remained unchanged. Compared to females, males had significantly larger maximal left atrial volumes (103 +/- 30 mL vs. 89 +/- 21 mL, p = .01) and left atrial stroke volumes (58 +/- 23 mL vs. 48 +/- 15 mL, p = .01). There was no difference in left atrial ejection fraction between the sexes. CONCLUSION: We have produced a large database of age-related normal ranges for left and right ventricular function and left atrial function in males and females. This will allow accurate interpretation of clinical and research datasets.     

Relationship of increased plasma atrial natriuretic factor and renal sodium handling during immersion-induced central hypervolemia in normal humans.

Although maneuvers augmenting atrial volume and/or stretch also augment plasma levels of atrial natriuretic factor (ANF), the role of ANF in modulating renal sodium and water handling has not been defined. Water immersion to the neck (NI) was employed to assess the ANF response to acute volume expansion in 13 seated sodium-replete normal subjects. ANF increased promptly and markedly from 7.8 +/- 1.8 to 19.4 +/- 3.8 fmol/ml, then declined to 6.3 +/- 1.4 fmol/ml after 60 min recovery. Concomitantly, NI increased urine flow rate (V) (2.0 +/- 0.6 to 7.0 +/- 0.9 ml/min; P less than 0.001) and sodium excretion (UNaV) (92 +/- 12 to 191 +/- 15 mu eq/min; P less than 0.001), and decreased PRA (-66 +/- 3%) and plasma aldosterone (-57 +/- 6%). Increases of plasma ANF ranged from less than 20% to over 12-fold. Similarly, the natriuretic response to NI varied markedly from none to 500%. There was a strong correlation between peak ANF and peak UNaV (r = 0.67; P less than 0.025), but none between peak V and peak plasma ANF (r = -0.10; P greater than 0.5). These findings suggest that an increase in plasma ANF contributes to the natriuretic response to NI, implying a physiological role for ANF in modulating volume homeostasis in humans.     

Impairment of respiratory muscle function in pulmonary hypertension

It has been suggested that impaired respiratory muscle function occurs in patients with PH (pulmonary hypertension); however, comprehensive investigations of respiratory muscle function, including the application of non-volitional tests, needed to verify impairment of respiratory muscle strength in patients with PH have not yet been performed. In the present study, respiratory muscle function was assessed in 31 patients with PH (20 females and 11 males; mean pulmonary artery pressure, 51+/-20 mmHg; median World Health Organization class 3.0+/-0.5; 25 patients with pulmonary arterial hypertension and six patients with chronic thromboembolic PH) and in 31 control subjects (20 females and 11 males) well-matched for gender, age and BMI (body mass index). A 6-min walking test was performed to determine exercise capacity. Volitionally assessed maximal inspiratory (7.5+/-2.1 compared with 6.2+/-2.8 kPa; P=0.04) and expiratory (13.3+/-4.2 compared with 9.9+/-3.4 kPa; P<0.001) mouth pressures, sniff nasal (8.3+/-1.9 compared with 6.6+/-2.2 kPa; P=0.002) and transdiaphragmatic (11.3+/-2.5 compared with 8.7+/-2.5 kPa; P<0.001) pressures, non-volitionally assessed twitch mouth (1.46+/-0.43 compared with 0.97+/-0.41 kPa; P<0.001) and transdiaphragmatic (2.08+/-0.55 compared with 1.47+/-0.72 kPa; P=0.001) pressures during bilateral anterior magnetic phrenic nerve stimulation were markedly lower in patients with PH compared with control subjects. Maximal inspiratory mouth (r=0.58, P<0.001) and sniff transdiaphragmatic (r=0.43, P=0.02) pressures were correlated with the 6-min walking distance in patients with PH. In conclusion, the present study provides strong evidence that respiratory muscle strength is reduced in patients with PH compared with well-matched control subjects. Furthermore, the 6-min walking distance is significantly linked to parameters assessing inspiratory muscle strength.     

The decline in blood glucose levels is less with intermittent high-intensity compared with moderate exercise in individuals with type 1 diabetes

OBJECTIVE: To compare the response of blood glucose levels to intermittent high-intensity exercise (IHE) and moderate-intensity exercise (MOD) in individuals with type 1 diabetes. RESEARCH DESIGN AND METHODS: Seven healthy individuals with type 1 diabetes were tested on two separate occasions, during which either a 30-min MOD or IHE protocol was performed. MOD consisted of continuous exercise at 40% Vo(2peak), while the IHE protocol involved a combination of continuous exercise at 40% Vo(2peak) interspersed with 4-s sprints performed every 2 min to simulate the activity patterns of team sports. RESULTS: Both exercise protocols resulted in a decline in blood glucose levels. However, the decline was greater with MOD (-4.4 +/- 1.2 mmol/l) compared with IHE (-2.9 +/- 0.8 mmol/l; P < 0.05), despite the performance of a greater amount of total work with IHE (P < 0.05). During 60 min of recovery from exercise, glucose levels remained higher in IHE compared with MOD (P < 0.05). Furthermore, glucose levels remained stable during recovery from IHE, while they continued to decrease after MOD (P < 0.05). The stabilization of blood glucose levels with IHE was associated with elevated levels of lactate, catecholamines, and growth hormone during early recovery from exercise (P < 0.05). There were no differences in free insulin, glucagon, cortisol, or free fatty acids between MOD and IHE. CONCLUSIONS: The decline in blood glucose levels is less with IHE compared with MOD during both exercise and recovery in individuals with type 1 diabetes.     

Exercise and posture-related changes of atrial natriuretic factor and cardiac function in diabetes

To study whether the release of atrial natriuretic factor (ANF) was altered in diabetic cardiac autonomic neuropathy (CAN), we determined plasma ANF concentrations during exercise and changes of posture in three groups of age- and sex-matched subjects (9 healthy subjects, 7 diabetic patients with CAN, and 7 diabetic patients without CAN). During exercise, plasma ANF concentrations rose threefold (P less than .001), and this increase was similar in the three groups. However, heart-rate response to exercise was impaired in the two groups of diabetic patients (P less than .004 vs. healthy subjects) but was more severely impaired in patients with CAN (P less than .03 vs. patients without CAN). In healthy subjects and patients without CAN, the increases of ANF during exercise correlated significantly with those of heart rate, systolic blood pressure, and rate-pressure product (P less than .01). In patients with CAN, the correlation was found exclusively with heart rate (P less than .01). An increase of ventricular ejection fraction occurred in all groups (P less than .001) but without showing statistical differences between groups. After 30 min of standing, a similar postural drop of plasma ANF concentrations (P less than .002) was observed in all subjects, reflecting preserved sympathetic control of vessels. In conclusion, exercise induces an increase of plasma ANF in diabetic patients with CAN. This increase, occurring similarly to healthy subjects, indicates that autonomic activation plays a minor role in ANF release during exercise. Impaired heart-rate response to exercise in patients without CAN suggests early damage of autonomic function, undetected by conventional rest tests.     

Adrenergic supersensitivity in Parkinsonians with orthostatic hypotension

The adrenergic status was studied through evaluation of platelet alpha 2-adrenoceptor number [( 3H]yohimbine binding sites), plasma catecholamine levels and blood pressure response to noradrenaline infusion in three groups of subjects (1) Parkinsonians with orthostatic hypotension; (2) Parkinsonians without orthostatic hypotension; and (3) control subjects. In Parkinsonians with orthostatic hypotension, systolic and diastolic blood pressures significantly (P less than 0.05) decreased from 144 +/- 9 and 76 +/- 6 mmHg in the lying position to 95 +/- 12 and 60 +/- 7 mmHg after 5 min standing. In these patients, noradrenaline plasma levels were significantly low (62 +/- 11 pg ml-1, (P less than 0.05) when compared with controls (219 +/- 13 pg ml-1) whereas no difference was noticed in Parkinsonians without orthostatic hypotension (195 +/- 14 pg ml-1). The noradrenaline dose required for a 25 mmHg increase in systolic blood pressure was significantly (P less than 0.01) lower in Parkinsonians with orthostatic hypotension (0.19 +/- 0.03 microgram kg-1) when compared with Parkinsonians without orthostatic hypotension (0.86 +/- 0.11 microgram kg-1) or with controls (0.68 +/- 0.1 microgram kg-1). Platelet alpha 2-adrenoceptor number was higher in Parkinsonians with orthostatic hypotension (313 +/- 52 fmol mg-1 protein) than in Parkinsonians without orthostatic hypotension (168 +/- 9 fmol mg-1 protein) or in controls (175 +/- 4 fmol mg-1 protein) with no change in Kd. This study demonstrates that in patients with Parkinson's disease, orthostatic hypotension is associated with an increase in both vascular sensitivity to noradrenaline and platelet alpha 2-adrenoceptor number.(ABSTRACT TRUNCATED AT 250 WORDS)     

Exercise-mediated peripheral tissue and whole-body amino acid metabolism during intravenous feeding in normal man

1. The effect of a daily submaximal exercise regimen on whole-body and peripheral tissue amino acid metabolism during weight-stable intravenous feeding (IVF) was evaluated in 11 normal volunteers. Five of the subjects performed 1 h of daily bicycle exercise at 75 W during IVF, while the remaining six subjects received IVF without daily exercise. Body nitrogen balance, leg and forearm plasma amino acid flux and whole-body kinetics were measured before and on day 10 of IVF using a [1-13C]leucine and [15N]glycine tracer. 2. At the end of the IVF period, exercised subjects demonstrated leg uptake of total amino acids (237 +/- 103 nmol min-1 100 ml-1 of tissue, mean +/- SEM) which was significantly (P less than 0.05) different than in non-exercised subjects (-1101 +/- 253 nmol min-1 100 ml-1 of tissue). 3. In the non-exercised forearm, a significant (P less than 0.05) decrease in total amino acid flux was observed in exercised subjects (-162 +/- 88 nmol min-1 100 ml-1 of tissue) compared with non-exercised subjects (-460 +/- 105 nmol min-1 100 ml-1 of tissue) on day 10 of IVF. 4. Efflux of 3-methylhistidine significantly (P less than 0.05) decreased from the leg in those subjects who performed daily exercise (-0.29 +/- 0.12 nmol min-1 100 ml-1 of tissue) compared with those subjects receiving IVF without daily exercise (-1.46 +/- 0.35 nmol min-1 100 ml-1 of tissue).(ABSTRACT TRUNCATED AT 250 WORDS)     

Atrial natriuretic factor in normal subjects and heart failure patients. Plasma levels and renal, hormonal, and hemodynamic responses to peptide infusion.

We investigated atrial natriuretic factor (ANF) in humans, measuring plasma immunoreactive (ir) ANF (in femtomoles per milliliter), and renal, hormonal, and hemodynamic responses to ANF infusion, in normal subjects (NL) and congestive heart failure patients (CHF). Plasma irANF was 11 +/- 0.9 fmol/ml in NL and 71 +/- 9.9 in CHF (P less than 0.01); the latter with twofold right ventricular increment (P less than 0.05). In NL, ANF infusion of 0.10 microgram/kg per min (40 pmol/kg per min) induced increases (P less than 0.05) of absolute (from 160 +/- 23 to 725 +/- 198 mueq/min) and fractional (1-4%) sodium excretion, urine flow rate (from 10 +/- 1.6 to 20 +/- 2.6 ml/min), osmolar (from 3.2 +/- 0.6 to 6.8 +/- 1.2 ml/min) and free water (from 6.8 +/- 1.6 to 13.6 +/- 1.6 ml/min) clearances, and filtration fraction (from 20 +/- 1 to 26 +/- 2%). Plasma renin and aldosterone decreased 33% and 40%, respectively (P less than 0.01). Systolic blood pressure fell (from 112 +/- 3 to 104 +/- 5 mmHg, P less than 0.05) in seated NL; but in supine NL, the only hemodynamic response was decreased pulmonary wedge pressure (from 11 +/- 1 to 7 +/- 1 mmHg, P less than 0.05). In CHF, ANF induced changes in aldosterone and pulmonary wedge pressure, cardiac index, and systemic vascular resistance (all P less than 0.05); however, responses of renin and renal excretion were attenuated. ANF infusion increased hematocrit and serum protein concentration by 5-7% in NL (P less than 0.05) but not in CHF.     

Analysis of the QT interval and its variability in healthy adults during rest and exercise

The aim of the present study was to quantify the variability of electrocardiographic QT and RR intervals during rest and dynamic physical exercise, and to interpret these variabilities in terms of relative autonomic modulation of the atrial and ventricular myocardium. We also sought to characterize the relationships between QT, heart rate-corrected QT (QT(c)) and RR intervals, and to consider their associations with differential autonomic regulation. Nine males and eight females of similar age (22.8 +/- 4.7 years), mass (75.5 +/- 13.0 kg) and aerobic fitness (43.6 +/- 7.7 ml kg(-1) min(-1)) (mean +/- SD) undertook progressive bicycle exercise. A three-lead Holter ECG was recorded continuously during pre-exercise, exercise and recovery, and mean values of RR, QT, QT(c), QT variability index (QTVI) and mean-normalized QT variance (QTVN) were determined. At the onset of exercise QTVI increased rapidly compared with rest and remained significantly elevated throughout exercise and recovery. There were significant differences between QT(a)VI and QT(e)VI (QT measured from Q wave onset to T wave apex (QT(a)) and T wave end (QT(e)), respectively) throughout the experimental protocol. QTVI was significantly reduced in males compared with females prior to exercise but was similar thereafter. We suggest that physical exercise perturbs the resting QT-RR relationship owing to the onset of differential parasympathetic modulation of the atrial and ventricular myocardium. QTVI can be used to quantify the relative autonomic influence on the atrial and ventricular myocardium during rest and exercise, and might be related to HR-dependent and HR-independent influences on the QT interval.     

The effects of low dose insulin infusions on the renin angiotensin and sympathetic nervous systems in normal man

To examine the effects of physiological insulin concentrations on the renin-angiotensin and sympathetic nervous systems, healthy volunteers were studied by the euglycaemic glucose clamp technique with sequential 60 min 0.5 and 1.0 mU kg-1 min-1 insulin infusions and, subsequently, by a control infusion simulating clamp conditions. Plasma renin activity increased from 0.8 +/- 0.1 ng ml-1 h-1 basally to 1.0 +/- 0.2 ng ml-1 h-1 during the 0.5 mU infusion to 1.4 +/- 0.1 ng ml-1 h-1 during the 1 mU infusion but did not change during control infusion (0.9 +/- 0.3 ng ml-1h-1 to 0.9 +/- 0.2 ng ml-1h-1 to 1.0 +/- 0.1 ng ml-1h-1) (P less than 0.001 insulin vs. control by ANOVAR). Plasma angiotensin II increased during insulin (21.2 +/- 1.8 to 25.2 +/- 2.3 to 29.3 +/- 2.4 pg ml-1) but not during control infusion (24.0 +/- 2.8 to 23.6 +/- 2.6 to 23.5 +/- 2.5 pg ml-1) (P less than 0.001 insulin vs. control). Serum aldosterone did not change significantly during either infusion (insulin: 239 +/- 89 pmol l-1 to 237 +/- 50 pmol l-1 to 231 +/- 97 pmol l-1, control: 222 +/- 79 to 237 +/- 50 to 213 +/- 97 pmol l-1). Plasma noradrenaline increased to a greater extent during insulin (1.03 +/- 0.2 to 1.14 +/- 0.8 to 1.27 +/- 0.17 nmol l-1) than control infusion (0.86 +/- 0.09 to 0.97 +/- 0.09 to 0.99 +/- 0.09 nmol 1-1 (P less than 0.01 insulin vs. control). Changes in mean systolic blood pressure during insulin infusion were significantly different from control (+ 3 vs. -4 mmHg, P less than 0.001). In conclusion acute hyperinsulinaemia within the physiological range increases circulating hormones of the renin-angiotensin and sympathetic nervous systems and also increases systolic blood pressure.