A. Berbinschi

Prevention of acute cyclosporine nephrotoxicity by atrial natriuretic factor after ischemia in the rat.

The present experimental study investigates whether the atrial natriuretic factor (ANF) is able to prevent the nephrotoxic effects of cyclosporine infused after 30 min of warm renal ischemia in the rat. At 2 hr after the end of ischemia, the glomerular filtration rate was improved by an ANF infusion: 390 +/- 19 microliters/min/100 g versus 298.3 +/- 31 microliters/min/100 g in ANF and saline-infused rats, respectively (P less than 0.05). Intravenous CsA infusion at a dose of 2.5 mg/kg/day produced a more pronounced fall in GFR when compared with the control: 205.4 +/- 19.7 microliters/min/100 g versus 298.3 +/- 31 microliters/min/100 g in CsA and saline, respectively (P less than 0.05). In contrast, a synthetic rat atriopeptin III (0.5 microgram/kg/min) infusion after ischemia given together with CsA prevented its deleterious effects upon GFR: 316 +/- 22 microliters/min/100 g versus 205.4 +/- 19 microliters/min/100 g in ANF/CsA versus CsA alone (P less than 0.001). Moreover, the natriuretic ANF effects remained unaffected by high plasma CsA peak levels: indeed, other parameters of renal function--urinary flow, urinary sodium concentration and excretion rates, and urinary sodium reabsorption and fractional excretion rates, were significantly increased in ANF alone or CsA/ANF groups. These preliminary results suggest that ANF may be useful in renal transplantation or in the management of patients given large doses of CsA (liver or heart transplant) since, despite nephrotoxic CsA levels (greater than 1500 ng/ml), ANF provides an improved GFR and tubular function after ischemia.

Effect of exercise on plasma atrial natriuretic factor and cardiac function in men and women.

Abstract In order to provide an integrated view of the physiology of atrial natriuretic factor (ANF) during exercise, we studied changes of its plasma concentrations in 13 normal subjects (seven males, six females) during three graded exercise levels and two periods of recovery (5 and 30 min), concomitantly with an assessment of cardiac function and ventricular volumes by multigated radionuclide angiography. Mean ANF levels (± SEM) increased in all patients at the second (P < 0·002) and third (P < 0·002) exercise levels, and after 5‐min recovery (P < 0·01): in males from 16 ± 7 to 30 ± 11 pg ml‐1at the third level, in females from 27 ± 12 to 61 ± 33 pg ml‐1. Normal values were observed after 30‐min recovery. Even if mean ANF levels were all higher in females, this difference did not reach statistical significance (P= 0·06). Significant decreases of ventricular volumes, as well as increases of ejection fraction and rate pressure product, were noted during exercise and were similar in both sexes. The kinetics of plasma ANF concentrations, compared with the increase of rate pressure product, was characterized by a latency and a remanence in recovery. This remanence, also present in the changes of ventricular volumes, supports the hypothesis that other factor(s) like catecholamines might still exert their influence after the exercise stops.

Effect of beta-adrenergic blockade on plasma atrial natriuretic factor and cardiac volumes during exercise in normal men.

Abstract Exercise stimulates the release of the atrial natriuretic factor (ANF). 1–3 The principal determinant of ANF release is atrial distension, 4 although adrenergic stimulation has also been implicated in the direct release of ANF. 5,6 Both of these mechanisms could account for the release of ANF during exercise. To elucidate the relative roles of these mechanisms, we determined the plasma ANF concentrations and cardiac volumes during exercise before and after β-adrenergic blockade with propranolol.

Beneficial effect of atrial natriuretic factor on ischemically injured kidneys in the rat. A new approach to improve early renal function.

In a rat experimental study we investigated whether the atrial natriuretic peptide by itself is able to improve early renal function after an ischemic injury. Two groups of Wistar male rats underwent a right nephrectomy and a left renal artery occlusion for 30 min and were infused for 2 hr after ischemia with isotonic saline or rat atrial natriuretic peptides (αANF: 28 amino acids (AP 28) and atriopeptin III (AP 24): 24 amino acids). ANF infusion increased the urinary flow (P<0.001), the urinary sodium concentration (P<0.001), the sodium excretion rate (P<0.0001), and improved the glomerular filtration rate (GFR) recovery (P<0.02) determined at the end of the 2-hr infusion period. AP 24 exhibited higher natriuretics activities than AP 28. The effect of both peptides upon GFR recovery was equivalent. These effects of ANF observed after acute ischemia suggest that this peptide may be beneficial on the resumption of renal function in the early phases following transplantation.

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 < .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 < .004 vs. healthy subjects) but was more severely impaired in patients with CAN (P < .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 < .01). In patients with CAN, the correlation was found exclusively with heart rate (P < .01). An increase of ventricular ejection fraction occurred in all groups (P < .001) but without showing statistical differences between groups. After 30 min of standing, a similar postural drop of plasma ANF concentrations (P < .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.

Evidence that atrial natriuretic factor is the humoral factor by which volume loading or mannitol infusion produces an improved renal function after acute ischemia. An experimental study in dogs.

This experimental study in dogs was designed to investigate whether maximal loading produces atrial natriuretic factor (ANF) release and whether this physiological peptide is involved in the improvement of the early renal function recovery after acute ischemia. The experimental protocol included a renal artery occlusion for 45 min in uninephrectomized dogs and the measurement of various parameters of renal function over 2-hr period after declamping. There were 3 experimental groups. In the control group (I) (n=10), the dogs received, after ischemia, an isotonic saline solution infusion at a rate of 0.2 ml/kg/min. In group II, (n=10) the animals underwent acute volemic expansion (1 ml/kg/min) with whole blood (hematocrit ≈25%) during the ischemic period, and after declamping, an isotonic saline infusion (NaCl 0.9%) infusion at the same rate as in the control group. In group III, (n=8) the dogs only received NaCl 0.9% (0.2 ml/kg/ min) before ischemia and α human ANF (3.6 ng/kg/min) dissolved in saline after ischemia and during the 2 hr of the renal recovery period. Volemic expansion induced a highly significant increase of the cardiac filling pressures concomittant with a prompt but transient 5–6-fold increase in ANF levels (357±92 pg/ml versus 60±4.1 pg/ml in controls at the time of declamping [P<0.05]). With these higher plasma ANF levels in overloaded animals, we observed, 2 hr after declamping, considerably improved renal function recovery in terms of glomerular filtration rate—37.5%±8.7 versus 11.8±3.9%; urinary sodium excretion rate—53.89 μeq/min versus 5.36±1.2 μeq/min …