Plasma catecholamine levels during water immersion in man

In ten normal subjects thermoneutral neck-out water immersion produced a highly significant natriuresis and diuresis mediated via an induced central hypervolaemia. During immersion suppression of plasma noradrenaline and adrenaline was observed but no change occurred in plasma dopamine levels. No correlation was found between the suppression of noradrenaline and the diuresis and natriuresis. The reduction in plasma noradrenaline observed may reflect a widespread diminution of sympatho-adrenal activity during water immersion. This reduction could be a consequence of the cardiovascular changes of immersion and may not be directly involved in the mechanism of the renal response.     

The role of nitric oxide in saline-induced natriuresis and diuresis in rats.

This study was designed to determine to what extent nitric oxide (NO) mediates the natriuretic and diuretic responses to acute isotonic saline (0.9 gram % NaCl) volume expansion (SVE, 0.5 ml min-1 kg-1). Studies were performed on 49 pentobarbital anesthetized (65 mg/kg) female Sprague-Dawley rats with or without a NO synthase inhibitor, Nomega-nitro-L-arginine (LNA). Group 1 received saline at 27 microliter/min for 1 hr (baseline) and then SVE for 1 hr; Groups 2-4 received LNA at 10, 150, and 200 microgram kg-1 min-1, respectively, for 1 hr followed by LNA + SVE. To determine to what extent inhibition of NOS would reverse an ongoing SVE-induced natriuresis and diuresis, Group 5 was saline-volume-expanded for hours 1 and 2 whereas Group 6 was administered SVE during the first hour and then SVE + 150 microgram kg -1 min-1 LNA during the second hour. SVE caused a significant (P < 0.05) increase in the glomerular filtration rate (GFR) of Group 1 and the LNA-treated rats (Groups 2-4). This SVE-induced increase in the GFR occurred despite the fact that baseline GFR was significantly lower in the two groups of rats that were infused with the highest doses of LNA (Groups 3-4). SVE was also associated with similar increases in urine flow rate, sodium and potassium excretion, and total osmolar excretion in Groups 1-4. On the other hand, mean arterial pressure (MAP) was significantly higher in Group 2 during SVE + LNA and during the baseline as well as during the SVE periods in Groups 3-4; MAP was also significantly elevated in Group 6 during SVE + LNA. Thus, despite the fact that MAP was higher in LNA-treated rats, sodium and urine flow rates were the same as in Group 1 (i.e., there was no evidence of a pressure natriuresis or diuresis in these animals). Along these lines, there was a small but significant positive linear correlation coefficient (r = 0.41, P = 0.05) between sodium excretion values and corresponding MAP values in SVE control rats but not in Groups 3-4 during SVE (r = 0.28, P = 0.26). The current data demonstrate that 1) NO does not mediate SVE-induced hyperfiltration in the rat, 2) NO also does not mediate SVE-induced natriuresis or diuresis, and 3), consistent with other reports, NO appears to mediate pressure natriuresis and diuresis.     

Cardiorenal reflexes do not attenuate the renal effects of infused atriopeptin in conscious dogs.

Low-dose infusions of atriopeptin produce only a modest diuresis and natriuresis. However, these infusions also decrease atrial pressures, a change that has been postulated to elicit an antidiuretic and antinatriuretic reflex from cardiac receptors and thereby to attenuate the direct renal effects of atriopeptin. To determine whether the renal effects of intravenously administered atriopeptin might be attenuated by a cardiorenal reflex, we infused alpha-human atrial natriuretic peptide (alpha-hANP) into cardiac-denervated and sham-operated (normal) conscious dogs. Following a control period, alpha-hANP was infused into each dog at 12.5, 25, or 50 ng.kg-1.min-1 for 1 hr. Infusion of alpha-hANP at 50 ng.kg-1.min-1 produced similar decreases in left atrial pressure in both normal and cardiac-denervated dogs (peak changes, -1.6 +/- 0.8 vs -2.4 +/- 0.9 mm Hg, respectively). Increases in urine flow (peak changes, 0.13 +/- 0.05 vs 0.20 +/- 0.06 ml/min) and sodium excretion (peak changes, 56 +/- 22 vs 70 +/- 11 microEq/min) also were not different between groups. The lower doses of alpha-hANP also elicited renal and hemodynamic responses in the cardiac-denervated dogs that did not differ significantly from those in the normal dogs. These data indicate that the diuresis and natriuresis elicited by intravenously administered alpha-hANP are not attenuated by a cardiorenal reflex in conscious dogs.     

Effect of chronic infusion of synthetic atrial natriuretic factor (ANF 8-33) in conscious two-kidney, one-clip hypertensive rats

Conscious two-kidney, one-clip hypertensive rats were chronically infused during 7 days with synthetic ANF (8-33) (1 microgram/hr/rat) by means of osmotic minipumps. The initial blood pressure of 183 +/- 4 mmHg gradually decreased to 116 +/- 5 mmHg the last 2 days of infusion. Pressure diuresis returned to normal and pressure natriuresis was attenuated. PRA was significantly lower (1.81 +/- 0.41 AI ng/ml/hr) than in not treated hypertensive rats (8.56 +/- 3.75 AI ng/ml/hr). A partial regression in cardiac hypertrophy was observed in the treated group. We suggest that the hypotensive response to ANF may be mainly due to vasodilatation, but the possibility that the decrease in PRA may play a partial role in lowering blood pressure, cannot be excluded.     

The renal actions of oxytocin in the conscious rat

The renal actions of oxytocin were studied in the conscious unrestrained rat infused with 0.077 M saline at a rate of 150 microliters/min. During the control period volume and sodium excretion reached stable equilibria, the rates being equal to those infused. Administration of oxytocin at 200 pmol/min produced plasma oxytocin levels of 26.0 +/- 2.1 pmol/l and caused a significant diuresis and natriuresis. Renal responses could also be seen with a lower dose of 30 pmol/min which produced plasma levels of 5.1 +/- 0.5 pmol/l while a dose of 15 pmol/min which produced no significant increase in the plasma oxytocin had no renal effect. It appears that oxytocin has a natriuretic action in concentrations within the physiological range.     

Chronic infusion of low doses of atrial natriuretic factor (ANF Arg 101-Tyr 126) reduces blood pressure in conscious SHR without apparent changes in sodium excretion

Conscious SHR and WKY rats were infused during 7 days with synthetic ANF (Arg 101-Tyr 126), 100 ng/hr/rat (35 pmol/hr/rat) by means of miniosmotic pumps. The SHR initial blood pressure of 177 +/- 5 mmHg gradually dropped to 133 +/- 3 and 142 +/- 4 mmHg the last two days of infusion. No significant change in blood pressure was observed in the ANF-infused WKY group. No apparent difference in natriuresis or diuresis was observed in ANF-infused SHR and WKY when compared with non-infused control groups. A slight but significant lower immunoreactive ANF concentration was found in the atria of SHR than in their normotensive controls. No difference in cardiac weight was found between infused and non-infused rats. It is suggested that the hypotensive response observed in SHR and not in WKY is due to a decrease in vascular peripheral resistance. Whether ANF is involved in the development and maintenance of high blood pressure in SHR remains to be elucidated.     

Role of renal nerves and vasopressin in renal responses to acute volume expansion in rats.

This study was to determine whether the presence or absence of renal nerves and vasopressin altered the diuretic and natriuretic responses to acute volume expansion. Two forms of volume expansion were used: (i) inflation of a small balloon in the veno-atrial junction and (ii) an infusion of isotonic saline at a rate of 1 ml/min for a period of 15 min, approximately 7% of body weight. Balloon inflation produced a significant diuresis from both the intact and denervated kidneys but only produced a significant natriuresis from the intact kidney. Volume expansion (infusion of saline) produced a significant diuresis and natriuresis from both intact and denervated kidneys. Blocking the V2 receptor for vasopressin with a V2-specific receptor blocker d(CH2)5[D-Ile2,Val4]AVP (40 micrograms/kg bolus dose followed by infusion of 4 micrograms/kg/min) did not alter the diuretic and natriuretic responses to volume expansion. However, the absence of renal nerves or the absence of actions of vasopressin produced a significant reduction in the capacity of the kidneys to increase the relative amount of diuresis or natriuresis, thus losing the control over output; i.e., absence of renal nerves only allowed 12-fold increase in diuresis to volume expansion compared with 25-fold in the intact state and absence of vasopressin only allowed 4.6-fold increase in diuresis to volume expansion compared with 25-fold in the intact state. Examining the "volume reflex" in terms of a control system trying to regulate fluid balance, the presence of either renal nerves or actions of vasopressin allows the volume regulating system a greater range in which to control the diuresis and natriuresis (making it possible to fine tune the output to much greater extent).     

The mechanism of polyethylene glycol-induced natriuresis in rats: role of atrial natriuretic hormone

A putative role of atrial natriuretic hormone (ANH) in a polyethylene glycol (PEG) 200-induced natriuresis was examined in conscious Wistar rats. Low molecular weight PEG 200 (0.5 or 1.0 ml/100g body weight) was orally administered to rats by gavage. Urine was collected during a 3 hr test period and blood was obtained at the end of each experiment for measurement of ANH, PRA, clearance studies and for indirect indices of plasma volume. Urinary excretion of sodium and volume increased while plasma ANH concentrations were markedly decreased in a dose-related manner following PEG 200 administration. The osmotic clearance was also elevated following PEG 200 administration. No significant change was observed in any of the parameters following high molecular weight PEG 8000. The observed decrease in ANH was associated with an apparent contraction of plasma volume despite the increased serum osmolality. These data indicate that the ANH inhibitory influence of the decreased plasma volume takes precedence over the stimulatory effect of the hyperosmolality and the latter is primarily responsible for the increased osmotic clearance and natriuresis observed in this model.     

Atrial natriuretic peptide influence on nitric oxide system in kidney and heart

Atrial natriuretic peptide (ANP) and nitric oxide (NO) induce diuresis, natriuresis and diminish vascular tone. Our previous studies showed NO system is involved in ANP hypotensive effect. The aim was to investigate ANP effects on renal and cardiac NO-synthase (NOS) activity. Rats were divided into two groups: group I, infused with saline (1 h, 0.05 ml/min); group II, received ANP bolus (5 microg/kg)+ANP infusion (1 h, 0.2 microg/kg x min). NADPH-diaphorase activity (NADPH-d) was determined in kidney and heart. NOS catalytic activity was determined in renal medulla and cortex and cardiac atria and ventricle by measuring the conversion of l-[U(14)C]-arginine to l-[U(14)C]-citrulline. In group I, NOS activity was determined in basal conditions and plus 1 microM ANP and in group II, NOS activity was determined in basal conditions. NADPH-d was higher in group II than in group I in glomeruli, proximal tubule, cortical and medullar collecting duct, right atria and left ventricle. NOS activity was increased by in vitro ANP addition and, in vivo, ANP infusion in all the studied tissues. ANP treatment increases renal and cardiac NO synthesis. This effect would be independent on the hemodynamic changes induced by ANP. The activation of NO pathway would be one of the mechanisms involved in diuretic, natriuretic and hypotensive effects of ANP.     

Comparison of the diuretic and natriuretic effects of dopamine in control and diabetes insipidus dogs. Effect of propranolol]

The diuretic effect of dopamine is unchanged in the dog with diabetes insipidus but the natriuretic effect of dopamine is shorter. With the normal dog propanolol delays the dopamine-induced diuresis and natriuresis but the magnitude of this double effect is unchanged. In the dog with diabetes insipidus, propanolol suppresses the dopaminergic diuresis and reduces the natriuresis.     

Effect of head-out immersion on plasma atrial natriuretic factor in man

This study was conducted to examine the role of atrial natriuretic factor (ANF) in the development of diuresis and natriuresis in response to the head-out immersion in 35 degrees C water. Six male subjects were hydrated (0.5% body wt), sat for 1 hr in air (preimmersion), were immersed in water to the neck for 3 hr, and then sat for 1 hr in air (postimmersion). In another series they were similarly hydrated and then sat for 5 hr in air for the time control. Urine and venous blood samples were collected hourly for creatinine and electrolyte measurements. In addition, the concentration of ANF was determined in unextracted plasma by a radioimmunoassay. The pattern of electrolyte excretion was evaluated on the basis of fractional excretion of filtered load. In the time control series, urine flow and fractional excretion of Na and K remained low throughout the 5-hr experimental period. On the other hand, urine flow increased significantly from the preimmersion level of approximately 2 to approximately 7 ml/min during the first hour of immersion (P less than 0.05), after which it decreased to approximately 5 ml/min during the second hour of immersion (P less than 0.05) and to approximately 2 ml/min during the third hour of immersion. Fractional excretion of Na increased continuously from preimmersion level of approximately 1.0 to approximately 1.8% during the second and third hours of immersion (P less than 0.05) and then decreased to 1.2% during the 1-hr postimmersion period. The plasma ANF remained low (approximately 75 pg/ml) during the 5-hr time control period. In the immersion series, plasma ANF increased significantly from the preimmersion level of approximately 80 to approximately 120 pg/ml during the entire 3-hr immersion period and then returned to the preimmersion level during 1 hr postimmersion. These results indicate that the immersion diuresis and natriuresis are indeed associated with the increased ANF release. However, it can not be ascertained from the present study if the increased ANF contributes directly to these renal responses to immersion or in concert with other mediators.     

Increased severity of the acute renal failure induced by HgCl2 on rats with reduced renal mass

In rats unilaterally nephrectomized 2 days before and sham operated controls, an acute fenal failure (ARF) has been induced by subcutaneous HgCl2 injection. The uninephrectomized animals showed a more severe ARF than the sham operated, 60% of the former and 10% of the controls became anuric 48 hours after ARF induction. The increased diuresis and natriuresis produced by acute saline overload did not improve the severity of the ARF. The marked difference in the evolution of this model of ARF with respect to the glycerol induced ARF, which is ameliorated by reduction of renal mass, emphasizes the different pathogenetic mechanism of these two experimental models.     

Red cell ouabain binding sites, Na+K+-ATPase, and intracellular Na+ as individual characteristics

Healthy male volunteers were infused for three hours with either a dopamine hydrochloride solution at a rate of 4 ug/kg/min or with normal saline. Plasma amine oxidase and platelet MAO activity towards benzylamine both increased in response to intravenous dopamine. There was no increase in enzyme activity when dopamine was added to the platelet and plasma enzymes in vitro. This heretofore unreported increase in the oxidative deaminating capacity of the human organism may represent an adaptive physiologic response to the high circulating levels of dopamine and provides further evidence for a possible functional significance of these enzymes in man.     

Heart atrial auriectomy reduces the diuretic and natriuretic responses to a hypertonic saline load

Acute bilateral atrial auriectomy in anesthetized dogs reduced diuresis and natriuresis induced by both extracellular fluid volume expansion with isotonic saline and a hypertonic saline load. Since a hypertonic saline load, in contrast to isotonic saline infusion, was not accompanied by a significant increase in central venous pressure it is proposed that either increased plasma osmolality or plasma sodium concentration (or both) participate in the modulation of the atrial natriuretic mechanism.     

Evidence for hormonal participation in the natriuretic and kaliuretic responses to intraventricular hypertonic saline and norepinephrine.

To examine if hypothalamic or pituitary hormones are involved in the induction of the natriuresis which follows the injection of hypertonic saline or norepinephrine into the third ventricle, lesions were placed in the median eminence and the responses to intraventricular norepinephrine or hypertonic saline were evaluated. Sham lesions in which the electrode was lowered into the brain but stopped short of the hypothalamic region did not interfere with the natriuresis, kaliuresis, and antidiuresis induced by the third ventricular injection of either hypertonic sodium chloride or norepinephrine. Lesions in the median eminence which induced diabetes insipidus as evidenced by an increase in water consumption to approximately four times normal completely abolished the natriuresis and kaliuresis in response to intraventricular hypertonic saline or norepinephrine and diminished the antidiuresis. The observations suggest the possibility that a natriuretic hormone(s) is involved in the induction of central natriuresis.     

The role of posture on the changes in plasma atrial natriuretic factor and arginine vasopressin levels during immersion

In seven healthy male volunteers we investigated changes in plasma atrial natriuretic factor [( ANF]), arginine vasopressin [( AVP]) and plasma volume (PV) during supine immersion. Twenty minutes head-out water immersion in a supine position in a thermo-neutral water bath attenuated the increase in PV induced by 20 min in a supine position in air, but increased the mean plasma [ANF] from 32.0 pg.ml-1, SEM 5.1 to 53.3 pg.ml-1, SEM 3.6 and decreased the mean plasma [AVP] from 1.4 pg.ml-1, SEM 0.1 to 0.9 pg.ml-1, SEM 0.04. Simultaneously, diuresis and natriuresis increased markedly. During a 20-min control period in the supine posture without immersion, PV, plasma [ANF] and [AVP] remained unaffected while diuresis and natriuresis did not increase to the same extent. These data suggest that an increase in the central blood volume induced by a weak external hydrostatic pressure during supine immersion triggered the changes in plasma [ANF] and [AVP] and that the increase was probably due to a shift of blood volume from peripheral to central vessels. The changes in plasma [ANF] contributed to the changes in natriuresis.     

Molecular advantage of diferric transferrin in delivering iron to reticulocytes: a comparative study

Administration of aprotinin, a kallikrein inhibitor, to anesthetized rats infused with 0.9% saline solution to expand the extracellular fluid volume resulted in blunted natriuresis and diuresis. Urine flow declined from 27.1 +/- 2.6 to 8.0 +/- 0.9 microliter/min/100 g body wt while sodium and potassium excretion were reduced 63 and 45%, respectively (P less than 0.01). Mean blood pressure and glomerular filtration rate were not significantly altered by aprotinin. Acute or chronic pretreatment with DOCA, to enhance kinin synthesis, failed to modify the renal excretory response to aprotinin suggesting that saline loading alone was able to induce kinin generation fully in these rats. The results indicate that aprotinin enhanced the reabsorption of filtrate in rats expanded with isotonic saline and imply an influence of renal kinins on the tubular transport of salt and water.     

Changes in urine volume and urinary electrolyte excretion after intracerebroventricular injection of arecoline and hemicholinium-3

Activation of cholinergic neurons in specific brain regions evokes a hypernatriuretic response, which appears to be atropine-sensitive and, perhaps, independent from the renal innervation. However the role of cholinergic neurons in central control of renal function is not well understood. The purpose of this study was to further investigate whether brain acetylcholine stores are able to influence kaliuresis and natriuresis in conscious rats. Therefore, the renal response to cholinergic drugs was examined in Wistar rats which underwent to a 0.15 M NaCl solution (saline) load administered by gavage. Central injection of arecoline, a muscarinic agonist, produced a dose-dependent reduction in water diuresis and a highly significant increase in sodium excretion within two hours from the oral saline load. An intracerebroventricular (ICV) injection of methylatropine completely blocked both the antidiuretic and the natriuretic response induced by arecoline. Hemicholinium-3 (HC), centrally administered at a dose (34.8 nmol) known to be capable of inducing a maximal depletion of brain acetylcholine, elicited a time-dependent antidiuretic effect accompanied by a highly significant reduction in potassium and sodium urinary excretion. Therefore, we suggest that brain cholinergic neurons are involved in the regulation of the electrolyte balance.     

Effects of atrial natriuretic peptides and furosemide in conscious dogs

Effects of ANF(8-33) and Auriculin A on renal variables were investigated in conscious water-diuretic dogs. The two substances were injected intravenously (1.08 micrograms/kg in 3 min) or ANF(8-33) was infused (0.2 microgram/kg X min in 20 min). The effects were compared to those of an equinatriuretic dose of furosemide (1.0 microgram/kg X min). Injections caused increases in sodium excretion, diuresis, and osmolar clearance. No significant change in exogenous creatine clearance (CCREA) occurred. Infusion of ANF(8-33) decreased blood pressure by 14% (P less than 0.01) and increased sodium excretion by a factor of 10 (P less than 0.01). The natriuresis was a function of increases in diuresis and urinary sodium concentration, the latter by a factor of 6 (P less than 0.01). Diuresis and free-water clearance (CH2O) increased by 60% (P less than 0.01), but urine osmolality did not change significantly. After the infusion a significant decrease in PAH clearance (CPAH) (P less than 0.01) was observed. Filtration fraction (FF) did not change. The furosemide natriuresis appeared later than that of ANF without significant deviations in diuresis, CH2O, CCREA, CPAH, and FF; urine osmolality increased by 35% (P less than 0.01). The effects of ANF(8-33) differ from those of furosemide in several ways. First, the onset of natriuresis is faster, second, the natriuresis is associated by marked increases in diuresis and free-water clearance but not in urine osmolality; and third, natriuresis is followed by a reduction in renal blood flow. The rapid natriuresis of ANF can occur without changes in glomerular filtration rate.     

Effect of pancreatic polypeptide-antiserum on bombesin-stimulated pancreatic exocrine secretion in dogs

Bombesin is a potent stimulus of both pancreatic protein secretion and plasma pancreatic polypeptide (PP) release in dogs. Physiological plasma levels of PP have been shown to inhibit pancreatic exocrine secretion in dogs. We examined the question whether the concomitant release of PP exerts a suppressive action on the pancreatic exocrine response to bombesin in dogs by measuring pancreatic exocrine secretion with and without in vivo immunoneutralization of PP with a high affinity PP-antiserum. Bombesin was infused in a dose of 150 ng/kg·hr, resulting in a rise of plasma PP from 24±5 to 224±25 pM (p<0.01). Before this bombesin infusion, 7 ml of normal rabbit serum had been administered to the dogs (n=8). At a later stage, the study was repeated after administration of 7 ml of PP-antiserum to the same animals. The bombesin induced increase in pancreatic exocrine secretion during administration of PP-antiserum (flow rate 24±10 ml/hr, protein output 1.35±0.43 g/hr, and bicarbonate output 3.25±1.42 mmol/hr) was not significantly different from that during control rabbit serum (flow rate 21±7 ml/hr, protein output 1.26±0.38 g/hr, and bicarbonate output 3.18±1.10 mmol/hr). It is therefore concluded that the pancreatic exocrine response to bombesin is not affected by the concomitant secretion of PP.