Relationship between renal sympathetic activity and diuretic effects of atrial natriuretic peptide (ANP) in the rat

The effects of various adrenergic agonists and antagonists on the diuretic/natriuretic effects of rANP (103-125) were investigated in conscious and anaesthetized normotensive rats. Pharmacological sympathetic inhibition by reserpine completely inhibited the diuretic/natriuretic effects of ANP. However, surgical renal nerve denervation did not influence the renal response to ANP. Further studies using various pharmacological agents which interfere with adrenergic activity revealed that the diuretic mechanism of action differed between conscious and anaesthetized animals. In the anaesthetized group only, dopamine (D1) blockade reduced ANP-induced diuresis. In the conscious as well as anaesthetized rats, however, pre-synaptic dopamine (D2) stimulation and alpha 2-adrenergic receptor blockade effectively inhibited the renal response to ANP. The results of this study are compatible with the notion that ANP acts indirectly within the kidney via interaction with dopamine-containing neuronal or non-neuronal structures in the kidney.     

The dopamine receptor antagonist haloperidol blocks natriuretic but not hypotensive effects of the atrial natriuretic factor

Studies were performed on anesthetized male Münich-Wistar rats to investigate the influence of the dopamine (DA) receptor antagonist haloperidol on the natriuretic response to infusion of a synthetic atrial natriuretic factor. The whole kidney glomerular filtration rate (GFR), urinary excretion of electrolytes, and arterial blood pressure (BP) were therefore measured in groups of animals pretreated with haloperidol or vehicle and given a continuous intravenous infusion of atrial natriuretic peptide (ANP; 28 amino acids). Forty-five minutes of ANP infusion at 10 micrograms h-1 kg-1 body wt did not increase GFR (change from 1.14 +/- 0.08 to 1.15 +/- 0.05 ml min-1 g-1 kidney wt). Sodium excretion (UNaV) increased more than four-fold from 0.037 +/- 0.008 to 0.165 +/- 0.070 mumol min-1 g-1 kidney wt (P less than 0.01). Potassium excretion (UKV) increased by 86% (P less than 0.001) and the urine flow rate (V) increased transiently by 63% (P less than 0.05) and did not differ from the control value during the last 15 min of ANP infusion. The urinary sodium concentration (UNa) increased almost three-fold, while BP decreased by 14%. There was no change in urine osmolality. In animals pretreated with haloperidol (1 mg kg-1 body wt), 45 min of ANP infusion did not significantly alter GFR (from 1.10 +/- 0.08 to 0.98 +/- 0.09 ml min-1 g-1 kidney wt). The UNaV did not increase significantly (change from 0.026 +/- 0.006 to 0.030 +/- 0.009 mumol min-1 g-1 kidney wt). The UKV was not elevated by ANP infusion.(ABSTRACT TRUNCATED AT 250 WORDS)     

Denervated and intact kidney responses to saline load in awake and anesthetized dogs.

The function of the innervated and denervated kidney was examined in clearance studies with unilaterally renal-denervated conscious and anesthetized dogs before and after saline loading. Barbiturate anesthesia distinctly depressed hemodynamics and excretory function of both kidneys and increased the difference between the denervated and innervated organ. In conscious moderately hydrated dogs the denervated kidney excreted slightly more sodium and water, while after saline loading higher excretion was observed on the innervated side. The denervated-to-innervated kidney ratios for UNaV, UNaV/100 ml GFR, and urine flow fell significantly from mean control values of 1.27, 1.27, and 1.20, respectively, to 0.80, 0.87, and 0.77 after extracellular volume expansion. Similar alterations of the ratios were observed in anesthetized dogs, but higher excretion of the denervated kidney persisted after saline loading. It is concluded that the greater natriuretic response of the intact kidney to saline infusion was due to inhibition of sodium-retaining action of renal efferent nerve activity by acute extracellular volume expansion.     

Effects of atrial natriuretic peptide (ANP) during converting enzyme inhibition

Studies were performed on anesthetized adult Münich-Wistar rats to investigate the role of angiotensin II in the natriuretic response to synthetic atrial natriuretic peptide (ANP, 28 amino acids). For this purpose the whole kidney glomerular filtration rate (GFR) and urinary excretion of electrolytes were measured in groups of animals pretreated with the converting enzyme inhibitor captopril (3 mg h-1 kg-1 body wt) or vehicle and then given a continuous intravenous infusion of ANP at 10 micrograms h-1 kg-1 body wt. In the vehicle-pretreated animals, 45 min of ANP infusion did not change GFR (control value 1.17 +/- 0.11, experimental value 1.17 +/- 0.06 ml min-1 g-1 kidney wt). Sodium excretion (UNaV) increased more than three-fold from 0.036 +/- 0.010 to 0.134 +/- 0.058 mumol min-1 g-1 kidney wt (p less than 0.05) and potassium excretion (UKV) increased from 0.481 +/- 0.055 to 0.946 +/- 0.068 mumol min-1 g-1 kidney wt (P less than 0.05). Urine osmolality (UOsm) remained unchanged, while the blood pressure (BP) decreased by 15%. In animals pretreated with captopril, ANP infusion led to a decrease in GFR from 1.27 +/- 0.11 to 1.05 +/- 0.09 ml min-1 g-1 kidney wt (P less than 0.05). Despite this effect, UNaV increased more than two-fold from 0.076 +/- 0.020 to 0.193 +/- 0.087 mumol min-1 g-1 kidney wt (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Contribution of Endothelial Nitric Oxide Synthase in the Blunted Renal Responses to Volume Expansion in Diabetic Rats

The renal excretory responses to volume expansion (VE), by 10 % body wt, were determined in groups of anaesthetised streptozotocin-induced diabetic rats with one denervated and one innervated kidney in the presence and absence of nitric oxide synthase (NOS) inhibitors. VE in diabetic rats increased (P < 0.001) cumulative urine sodium excretion (CuU(Na)V) to 104 +/- 9 and 69 +/- 6 micromol min(-1) (g kidney wt)(-1) in the denervated and in the innervated kidneys, respectively, which were both less (P < 0.001) than in the non-diabetic rats, at 225 +/- 14 and 148 +/- 14 micromol min(-1) (g kidney wt)(-1), respectively, in the denervated and the innervated kidney. The non-selective NOS inhibitor, N(G)-nitro-L-arginine-methyl-ester (L-NAME) given to the diabetic rats with intact renal innervation enhanced CuU(Na)V after VE by 43 % (P < 0.001), while the combination of L-NAME and renal denervation restored CuU(Na)V to a value comparable to that of non-diabetic rats. In diabetic rats treated with either a relatively selective inhibitor for the neuronal isoform of NOS, 7-nitroindazole, or a relatively selective inhibitor for the inducible isoform of NOS, aminoguanidine, CuU(Na)V after VE was similar to the untreated diabetic rats irrespective of whether or not the renal nerves were present. This investigation demonstrated that NO production contributed, at least partly, to the depressed ability to excrete a saline load in diabetes mellitus. The endothelial isoform of NOS was most probably responsible for generating NO which caused the blunted excretory responses. The ability of NO to attenuate the excretory responses to volume expansion was an action independent of the renal innervation status. Experimental Physiology (2001) 86.4, 481-488.     

Dynamic exercise attenuates spontaneous baroreceptor reflex sensitivity in conscious rats

In humans, it has been reported that dynamic exercise attenuates spontaneous baroreceptor reflex sensitivity (sBRS), which is an index of the gain of the baroreceptor-cardiac reflex. We demonstrated previously that endogenously produced NO from endothelial nitric oxide synthase (eNOS) within the nucleus tractus solitarii (NTS), the central terminal site of baroreceptor afferents, depressed sBRS. In this study, we investigated whether eNOS activity within the NTS plays any role in down-modulating the sBRS during dynamic exercise. In conscious Wistar rats arterial pressure and heart rate (HR) were monitored continuously and chronically using radiotelemetry before and during wheel cage running at 6 m min(-1) for 10 min. sBRS was determined by a time-series method. During dynamic exercise systolic blood pressure (SBP) and HR were significantly increased (SBP: 138 +/- 2 vs. 125 +/- 2 mmHg, P < 0.001; HR: 447 +/- 6 vs. 362 +/- 8 beats min(-1), P < 0.001) while sBRS was significantly decreased (0.53 +/- 0.03 vs. 1.08 +/- 0.08 ms mmHg(-1), P < 0.001). In sino-aortic denervated rats the change in SBP in response to dynamic exercise was significantly larger than that in baroreceptor-intact rats (denervated: 21.6 +/- 2.5 mmHg; intact: 12.0 +/- 2.8 mmHg, P < 0.05). In contrast, denervation made no difference to the change in HR. Although disabling eNOS activity in the NTS by adenoviral-directed expression of a dominant negative mutant form of eNOS increased resting sBRS (1.48 +/- 0.20 vs. 1.09 +/- 0.15 ms mmHg(-1), P < 0.05), the absolute level reached during dynamic exercise was identical to control. These results demonstrate that during dynamic exercise (i) the sBRS decreases around the operating point of the baroreceptor-cardiac reflex function curve in normotensive rats, (ii) the baroreceptor reflex operates to limit the rise in arterial pressure, and (iii) the attenuation of sBRS is not mediated by changes in eNOS activity within the NTS.     

Baroreflex participation of cardiovascular response to E. coli endotoxin

The purpose of this experiment was to evaluate the effects of the arterial baroreceptor buffering capacity on cardiovascular parameters during hypotension caused by E. coli endotoxin in anesthetized dogs. In the control group, mean blood pressure and cardiac output fell significantly from 104 +/- 10 mmHg to 63 +/- 7 mmHg and 1.17 +/- 0.16 l/min to 0.67 +/- 0.08 l/min, respectively, 60 min after intravenous injection of endotoxin (1 mg/kg). Central venous pressure also decreased significantly after the injection. Total peripheral resistance and portal vein pressure increased significantly immediately after the injection, and then returned toward baseline levels. The time course of changes in these five cardiovascular parameters after the injection of endotoxin was the same as that in dogs with sino-aortic denervation. Following the injection of endotoxin, stroke volume and left ventricular dP/dt fell significantly in both control and denervated dogs; however, these decreases in the denervated group were significantly greater. These findings suggest that the arterial baroreceptors may play a role in the poor compensatory response to hypotension induced by endotoxin, at least, in the cases of mean blood pressure, cardiac output, total peripheral resistance, central venous pressure, and portal vein pressure.     

Supersensitivity of the renal tubule to catecholamines in the chronically denervated canine kidney

Experiments were performed on anesthetized dogs to study whether or not renal tubules of the chronically denervated kidney show supersensitivity toward circulating catecholamines. In one kidney the influence of plasma catecholamines was inhibited by intrarenal administration of the alpha adrenergic receptor blocker phenoxybenzamine (POB, 2 g/min), and renal parameters of the infused kidney were compared to those of the contralateral noninfused organ. Before POB infusion urine flow (V), urinary sodium and potassium excretion (U_NaV, U_KV) as well as clearance of inulin and PAH (GFR, C_PAH) were similar in infused and contralateral kidneys in all the groups studied. In dogs (n=8) with two innervated kidneys POB infusion elevated V and U_NaV by 53±13% and 102±34% (p<0.05). In dogs (n=8) with acute bilateral renal denervation POB administration failed to alter any of the measured parameters. In contrast, V and U_NaV from chronically denervated kidneys (n=7) were increased after POB infusion by 40±9% and 103±34% (p<0.05). Glomerular filtration rate, C_PAH and U_KV were not changed by alpha adrenoceptor blockade in any of the groups. In an additional group of animals (n=8) acute unilateral renal denervation increased V and U_NaV to a significantly higher extent (by 282±85% and 330±106%) than POB administration did in the innervated kidney and elevated U_KV (44±10%), too. It is concluded that supersensitivity to catecholamines developed in renal tubules of the chronically denervated dog kidney and, in consequence, circulating catecholamines at elevated plasma levels caused by surgery were capable of increasing tubular reabsorption of sodium and water.     

Regional sympathetic denervation affects the relation between canine local myocardial blood flow and oxygen consumption

Myocardial blood flow and oxygen consumption are heterogeneously distributed. Perfusion and myocardial oxygen consumption are closely correlated in the normal heart. It is unknown how this metabolism-perfusion relation is influenced by sympathetic denervation. We investigated this question in seven chloralose-anaesthetized dogs, 3-4 weeks after regional sympathetic denervation of the left circumflex coronary artery area of supply of the left ventricle. Measurements were made of local myocardial blood flow (MBF, in ml min(-1) (g dry wt)(-1)), measured with microspheres, and myocardial oxygen consumption ( , in mumol min(-1) (g dry wt)(-1)) in the same location, calculated from the (13)C spectrum of tissue extracts after intracoronary infusion of 3-(13)C-lactate. Since both innervated and denervated regions are subject to the same arterial pressure, lower blood flow indicates higher resistance. Mean MBF was 5.56 ml min(-1) (g dry wt)(-1) (heterogeneity of 3.47 ml min(-1) (g dry wt)(-1)) innervated, 7.48 ml min(-1) (g dry wt)(-1) (heterogeneity of 3.62 ml min(-1) (g dry wt)(-1)) denervated (n.s.). Significant linear relations were found between MBF and M Vo2 of individual samples within the innervated and denervated regions. The slopes of these relations were not significantly different, but the adjusted mean was significantly higher in the denervated regions (+1.92 ml min(-1) (g dry wt)(-1), an increase of 38% of the mean MBF at the pooled mean M Vo2, P = 0.028, ANCOVA). The ratio MBF/M Vo2(in ml micromol(-1)) was significantly higher, being 0.296 +/- 0.167 ml micromol(-1) in the denervated region compared with the innervated region, 0.216 +/- 0.126 ml micromol(-1), P = 0.0182, Mann-Whitney U test. These results indicate that sympathetic tone under chloralose anaesthesia imposes a moderate vasoconstrictive effect in the myocardium that is not detected by comparison of the mean blood flow or resistance.     

Effects of high NaCl diet on arterial pressure in Sprague-Dawley rats with hepatic and sinoaortic denervation

The Na(+) receptor that exists in the hepatoportal region plays an important role in postprandial natriuresis and the regulation of Na(+) balance during NaCl load. Thus it would be considered that a dysfunction of the hepatic Na(+) receptor might result in the elevation of arterial pressure under a condition of high NaCl diet. To elucidate this hypothesis, arterial pressure was continuously measured during three weeks of high NaCl diet (8% NaCl) in four groups of rats: (i) intact rats, (ii) rats with hepatic denervation (HD), (iii) rats with sinoaortic denervation (SAD), and (iv) rats with SAD+HD. During a 1-week normal NaCl diet period, there was no difference in arterial pressure among the four groups. A high NaCl diet had no influence on arterial pressure in intact or HD rats; however, it significantly increased by 11 +/- 3 mmHg in SAD rats. The addition of HD to SAD had no synergistic effect on arterial pressure; i.e., in SAD+HD rats, mean arterial pressure increased by 13 +/- 1 mmHg. In conclusion, sinoaortic baroreceptor, but not hepatic Na(+) receptor, has a significant role in the long-term regulation of arterial pressure on a high NaCl diet.     

Contribution of renal prostaglandins to the natriuretic action of bradykinin in the dog.

To study the effects of stimulation of renal prostaglandin biosynthesis by bradykinin, we assessed the changes in renal functions induced by intrarenal infusion of bradykinin (10 ng . min-1 . kg-1) in the dog anesthetized with pentobarbital before and during inhibition of prostaglandin synthesis by sodium meclofenamate (5 mg/kg). Before meclofenamate administration, bradykinin augmented the urinary output of a "PGE"-like substance from 1.00 +/- 0.25 to 3.88 +/- 1.09 ng/min (P less than 0.05) and increased renal blood flow by 65 +/- 9 ml/min (P less than 0.001), urine flow by 0.55 +/- 0.23 ml/min (P less than 0.05), and sodium excretion by 64.8 +/- 18.0 mueq/min (P less than 0.01). Administration of meclofenamate did not affect the bradykinin-induced increase in renal blood flow and urine volume, but suppressed the evoked output of "PGE" and reduced the associated natriuresis, i.e., sodium excretion increased by only 11.1 +/- 4.8 mueq/min (P greater than 0.05). In contrast, meclofenamate did not affect the natriuresis effected by an equidilator dose of PGE2 (5 ng . min-1 . kg-1) infused intrarenally. These observations suggest that a product of prostaglandin synthetase produced by the kidney during intrarenal infusion of bradykinin contributes to the natriuretic action of the peptide.     

Hepatic portal vein infusion of glucose on sodium excretion in the rat.

Anesthetized rats were prepared with catheters in the hepatic portal (HPV) and femoral (FEM) veins and in the bladder or ureters. In some experiments the left kidney was denervated. HPV infusion of 1 M glucose at 2 ml/h for 20 min increased Na excretion by the kidney when given as a second infusion. Bilateral cervical vagotomy eliminated the increase in Na excretion during glucose infusion and uncovered a delayed decrease in Na and K excretion. Renal denervation attenuated the increase in Na excretion to HPV glucose. FEM infusion of glucose had variable effects, increasing Na excretion only after vagotomy. The results are interpreted to suggest that central and vagal receptors tend to enhance Na excretionwhereas splanchnic nerve afferents and humoral mediator(s) have the opposite effect.     

Renal sodium reabsorption after acute renal denervation in the rabbit

1. Separate effects on the functions of left and right kidneys were examined after left-sided renal handling and acute denervation. Studies were done on pentobarbital-anaesthetized rabbits using clearance techniques to evaluate renal haemodynamics and water and electrolyte excretion.2. When compared with its counterpart, the handled kidney exhibited some decrease in function for at least 20 min. Recovery of most functions occurred in 40-60 min.3. The effects of denervation on renal functions were observed when the effects of handling had subsided. Renal plasma flow (R.P.F.) and glomerular filtration rate (G.F.R.) were not significantly changed, whereas the decrease in Na, K and water excretion, which was usually observed for no ascertained reason in the innervated kidney, was prevented.4. The magnitude of the denervation natriuresis was greater in these rabbits than in dogs studied previously; other functions studied were comparable in the two species.5. The results from thirty-five experiments are interpreted to indicate that denervation decreases Na reabsorption independently of G.F.R., perhaps by a direct effect on tubular transport, but more probably by a redistribution of filtration to nephrons of lesser reabsorptive capacity.     

Hepatic portal vein infusion of glucose on sodium excretion in the rat

Anesthetized rats were prepared with catheters in the hepatic portal (HPV) and femoral (FEM) veins and in the bladder or ureters. In some experiments the left kidney was denervated. HPV infusion of 1 M glucose at 2 ml/h for 20 min increased Na excretion by the kidney when given as a second infusion. Bilateral cervical vagotomy eliminated the increase in Na excretion during glucose infusion and uncovered a delayed decrease in Na and K excretion. Renal denervation attenuated the increase in Na excretion to HPV glucose. FEM infusion of glucose had variable effects, increasing Na excretion only after vagotomy. The results are interpreted to suggest that central and vagal receptors tend to enhance Na excretion whereas splanchnic nerve afferents and humoral mediator(s) have the opposite effect.     

Acute neutral endopeptidase inhibition is natriuretic in old rats.

Neutral endopeptidase 24.11 (NEP) inhibitors prevent breakdown of atrial natriuretic peptide (ANP), and may be useful therapeutically, in sodium overload states as often occurs in the aged. However, age-dependent changes in ANP/NEP may limit the activity of these agents in the elderly. To investigate this we conducted experiments in young, middle aged and old conscious male rats, studied in the baseline euvolemic state and during acute NEP inhibition (NEPI). NEPI produced a marked increase in sodium excretion (>100%) in all groups, regardless of age. A selective, potassium sparing effect was also seen, only in the middle-aged and old rats. Although baseline hemodynamics were affected by age with mean blood pressure, BP, and renal vascular resistance (RVR) being higher in old versus young (131+/-5 vs. 115+/-3 mmHg; P<0.05 and 29+/-3 vs. 20+/-1 mmHg/ml per min per 100 g body weight (BW); P<0.02, respectively); NEPI produced similar mild pressor and significant renal vasoconstrictor effects in all age groups. Despite the tendency of NEPI to reduce renal perfusion, this is an effective method of increasing sodium excretion in all age groups while the potassium sparing actions seen selectively in the older rats may increase the usefulness of NEPI as a diuretic agent for the elderly.     

Blood pressure and sleep in the rat in normotension and in neurogenic hypertension.

1. Blood pressure was recorded in normotensive rats (114 +/- 2 mmHg) and in those made hypertensive by baroreceptor denervation (135 +/- 4 mmHg) during natural sleep. The different states of the wakefulness-sleep cycle were identified by analysis of the frontal electrocorticogram, the cervical electromyogram and by behavioural changes. 2. During synchronized sleep the arterial pressure in the control animals usually remained unchanged as compared to values prevailing when the rats were awake and quiet. The blood pressure usually attained higher levels in the sino-aortically denervated rats during this state. 3. Coincidently with the short episodes of electrocortical desynchronization of the synchronized sleep the blood pressure exhibited rapid oscillations. These fluctuations were greater in the rats with neurogenic hypertension where there were large pressure drops. 4. During desynchronized (REM) sleep arterial pressure underwent marked oscillations. While in the control rats the pressure usually rose, the baroreceptor-denervated rats showed a severe reduction in pressure. Arterial pressure in denervated animals became lower than that of the control rats, 106 +/- 2 and 121 +/- 2 mmHg, respectively. 5. We interpret these results to mean that in the rat alterations in the sensitivity of the baroreceptor reflex could be an important factor in preventing the arterial pressure from rising to hypertensive levels during syndhronized sleep and from dropping to low values during desynchronized (REM) sleep.     

Renal function in Lophius americanus: effects of angiotensin II.

Arterial blood pressure, urine flow rate, and plasma and urine electrolytes were measured in the aglomerular goosefish (L. americanus) before, during, and after the intravenous infusion of angiotensin II (from 5 to 280 ng/min.kg body wt). Increases in arterial blood pressure were directly related to the logarithm of the angiotensin infusion rate (r = 0.62, P less than 0.005). Angiotensin also increased urine flow from 0.676 +/- 0.065 to 0.755 +/- 0.068 ml/h.kg body wt (P less than 0.005) and Na excretion from 41.0 +/- 5.5 to 54.4 +/- 7.0 mumol/h.kg body wt (P less than 0.001). In 17 of the 19 fish infused with angiotensin the diuretic and natriuretic effects were directly related to the logarithm of the infusion rate (r = 0.44, P less than 0.04 and r = 0.51, P less than 0.02, respectively). There was no relationship between the pressor and the diuretic or natriuretic effects of angiotensin II. These results are consistent with inhibitory effects of angiotensin on solute transport by aglomerular tubules.     

Renal interaction between sympathetic activity and ANP in rats with chronic ischaemic heart failure

The diuretic and natriuretic effects of r-alpha-ANP (99-126) were investigated in rats with chronic ischaemic heart failure (IHF) produced by left coronary artery ligation. The plasma concentration of immunoreactive ANP (IrANP) was significantly higher, 91.8 +/- 16.0 pm in the IHF rats compared to 31.0 +/- 4.9 pm in sham-operated controls. In the control rats, ANP infusion (0.25-1.0 micrograms kg 1 mm 1) increased urine flow rate (V) and urinary sodium (UNa V) excretion. At the highest dose level, both V and UNa V were increased approximately fivefold. The diuresis and natriuresis seen in the control group after the infusion of ANP were blunted in the IHF rats. A bilateral surgical renal denervation in the IHF rats did not alter the renal dopamine levels, but induced a significant decrease in renal noradrenaline content, and almost completely restored the renal responsiveness to the ANP infusions. We conclude that renal denervation reversed the blunted renal excretory response to ANP in IHF rats. Thus, in experimental IHF, there seems to be a functional antagonism between efferent renal sympathetic nerve activity and ANP.     

Different effects of furosemide on urinary excretion of prostaglandin E2 and F2 alpha in rabbits.

The effect of a constant infusion of furosemide (130 micrograms/min i.v. for 60 min, n = 8) was studied on urinary excretion of water, electrolytes and immunoreactive prostaglandin E2 (iPGE2) and iPGF2alpha in chloralose-urethane anesthetized rabbits. During the furosemide infusion sodium and water excretion increased ten-fold and the excretion of potassium and iPGE2 two to three times. The excretion of iPGF2alpha (0.06 +/- 0.03 micrograms/min/100 g kidney weight) was not significantly changed during the furosemide infusion but increased markedly after the infusion and reached a maximum (1.0 +/- 0.6 microgram/min/100 g) 30 to 45 min later, while the small increase in iPGE2 excretion at this time could be attributed to cross-reaction with PGF2alpha. The results indicate that PGE2 might possibly be involved directly in the action of furosemide, while PGF2alpha might participate in sodium and water conserving mechanisms in the rabbit kidney, activated by the drug induced diuresis.     

Increase in plasma sodium enhances natriuresis in response to a sodium load unable to change plasma atrial peptide concentration

The influence of plasma sodium concentration in the control of sodium excretion was investigated in conscious, water-diuretic dogs. NaCl was infused for 60 min as a hypertonic or isotonic solution at a rate of 60 mumol NaCl min-1 kg-1 body wt. Plasma sodium concentration rose only during hypertonic infusion (P less than 0.05). Sodium excretion increased markedly with both infusions (hypertonic, from 2.4 +/- 0.6 to 105 +/- 27 mumol min-1; isotonic, from 3.9 +/- 1.3 to 58 +/- 17 mumol min-1). Fractional sodium excretion increased more during hypertonic than during isotonic infusion. Hypertonic infusion decreased diuresis from 3.1 +/- 0.5 to 1.3 +/- 0.6 ml min-1, while isotonic infusion elicited an increase from 3.9 +/- 0.5 to 7.2 +/- 0.7 ml min-1. Plasma renin activity and plasma aldosterone decreased markedly in both series (P less than 0.05), the relative changes in the two series being very similar. Central venous pressure increased (2.8 +/- 0.7 to 4.5 +/- 1.0 mmHg) during isotonic infusion but not significantly during hypertonic infusion. Arterial pressure, heart rate and plasma levels of atrial natriuretic peptide and catecholamines did not change measurably in either series. It is concluded that simultaneous increases in extracellular volume and sodium concentration cause a larger natriuretic response than a change in volume alone, and that a 40-fold increase in sodium excretion may occur without measurable changes in plasma atrial natriuretic peptide concentration.