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.     

Mechanisms of mechanical load-induced atrial natriuretic peptide secretion: role of endothelin, nitric oxide, and angiotensin II

There are three members in the natriuretic peptide hormone family, atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP, brain natriuretic peptide), and C-type natriuretic peptide (CNP), that are involved in the regulation of blood pressure and fluid homeostasis. CNP is found principally in the central nervous system and vascular endothelial cells while ANP and BNP are cardiac hormones. ANP is synthesized mainly in the atria of the normal adult heart, while BNP is produced by both the atria and ventricles. The mechanisms controlling ANP release have been the subject of intense research, and are now fairly well understood. The major determinant of ANP secretion is myocyte stretch. Although much less is known about the factors regulating BNP release from the heart, myocyte stretch has also been reported to stimulate BNP release from both atria and ventricles. However, whether wall stretch acts directly or via factors such as endothelin-1, nitric oxide, or angiotensin II liberated in response to distension has not been established. Recent studies show that by stimulating endothelin type A receptors endothelin plays an important physiological role as a mediator of acute-volume load-induced ANP secretion from atrial myocytes in conscious animals. In fact, endogenous paracrine/autocrine factors liberated in response to atrial wall stretch rather than direct stretch appears to be responsible for activation of ANP secretion in response to volume load, as evidenced by almost complete blockade of ANP secretion during combined inhibition of endothelin type A/B and angiotensin II receptors. Furthermore, under certain experimental conditions angiotensin II and nitric oxide may also exert a significant modulatory effect on stretch-activated ANP secretion. The molecular mechanisms by which endothelin-1, angiotensin II, and nitric oxide synergistically regulate stretch-activated ANP release are yet unclear.     

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.     

Intracellular sodium modulates the state of protein kinase C phosphorylation of rat proximal tubule Na+,K+-ATPase

The natriuretic hormone dopamine and the antinatriuretic hormone noradrenaline, acting on alpha-adrenergic receptors, have been shown to bidirectionally modulate the activity of renal tubular Na+,K+-adenosine triphosphate (ATPase). Here we have examined whether intracellular sodium concentration influences the effects of these bidirectional forces on the state of phosphorylation of Na+,K+-ATPase. Proximal tubules dissected from rat kidney were incubated with dopamine or the alpha-adrenergic agonist, oxymetazoline, and transiently permeabilized in a medium where sodium concentration ranged between 5 and 70 mM. The variations of sodium concentration in the medium had a proportional effect on intracellular sodium. Dopamine and protein kinase C (PKC) phosphorylate the catalytic subunit of rat Na+,K+-ATPase on the Ser23 residue. The level of PKC induced Na+,K+-ATPase phosphorylation was determined using an antibody that only recognizes Na+,K+-ATPase, which is not phosphorylated on its PKC site. Under basal conditions Na+,K+-ATPase was predominantly in its phosphorylated state. When intracellular sodium was increased, Na+,K+-ATPase was predominantly in its dephosphorylated state. Phosphorylation of Na+,K+-ATPase by dopamine was most pronounced when intracellular sodium was high, and dephosphorylation by oxymetazoline was most pronounced when intracellular sodium was low. The oxymetazoline effect was mimicked by the calcium ionophore A23187. An inhibitor of the calcium-dependent protein phosphatase, calcineurin, increased the state of Na+,K+-ATPase phosphorylation. The results imply that phosphorylation of renal Na+,K+-ATPase activity is modulated by the level of intracellular sodium and that this effect involves PKC and calcium signalling pathways. The findings may have implication for the regulation of salt excretion and sodium homeostasis.     

Renal function after myocardial infarction and cardiac arrest in rats: role of ANP-induced albuminuria?

Renal function was measured by clearance technique before and after acute myocardial infarction (MI) induced by left coronary artery ligation in male Sprague–Dawley rats. The animals were anaesthetized with halothane-nitrous oxide, paralysed with pancuronium and artificially ventilated. All parameters were stable throughout the experiment in sham-operated time control animals (n = 8). After MI, rats developed left ventricular dysfunction with increased left ventricular end-diastolic pressure and decreased mean arterial pressure. MI produced antidiuresis and antinatriuresis without changes in glomerular filtration rate (GFR), lithium clearance or renal albumin excretion (n = 8). The antidiuretic and antinatriuretic responses to MI were similar in rats with chronic bilateral renal denervation (n = 5). Three additional rats with chronic bilateral renal denervation had cardiac arrest and were resuscitated with cardiac massage, i.v. lidocaine and intracardiac adrenaline administration. These animals showed a transient increase in urine flow rate, sodium and albumin excretion with maximum 30–60 min after resuscitation, while GFR and lithium clearance were normal. Since cardiac ischaemia and sympathetic stimulation are strong stimuli for the release of atrial natriuretic peptide (ANP), we examined if ANP (0.25, 0.50, and 1.00 μg kg^?1 min^?1, n = 8 per dose) affects urinary albumin excretion. ANP increased dose-dependently the urine/plasma concentration ratio of albumin relative to inulin, which suggests that ANP increases the glomerular permeability for albumin. We conclude that MI causes stimulation of renal tubular sodium and water reabsorption by a mechanism which is independent of intact renal innervation. MI does not produce any change in renal albumin excretion in rats, but transient albuminuria may be observed in rats following cardiac arrest and/or manoeuvres used in cardiac resuscitation. Since ANP produces albuminuria, we speculate that ANP may be an important mediator of albuminuria in states with elevated plasma concentrations of ANP.     

The collecting duct, dopamine and vasopressin-dependent hypertension

AVP not only increases osmotic water permeability (Pf) in the rat cortical collecting duct (CCD), but also acts synergistically with aldosterone to augment sodium reabsorption (JNa). These effects are inhibited by catecholamines via alpha2 adrenergic receptors, and by dopamine. We review here studies designed to determine the mechanism and receptor involved in dopamine action. The inhibitory effect of dopamine on Na+ and water transport was found to be reversible, and was not produced by agonists specific to D1A and D1B receptors. D2-type (D2, D3 or D4) receptors and activation of the GTP-binding protein Gi were implicated by the observation that dopamine had no inhibitory effect when JNa and Pf were stimulated by a cyclic AMP analogue plus isobutylmethylxanthine. The only dopaminergic antagonist that reversed the inhibitory effect of dopamine was clozapine, which is relatively D4-specific. We also found that dopamine or D1-specific agonists by themselves had no effect on cAMP production. However, dopamine inhibited the high rate of AVP-dependent cAMP production, and this effect of dopamine was reversed by clozapine but not other antagonists or by inhibitors of protein kinase C. The D4 receptor was observed in western blots of renal cortical proteins, and it was localized to the collecting duct by RT-PCR and immuno-histochemistry using a D4-specific antibody. These results show that at least a portion of the natriuretic effect of dopamine can be attributed to inhibition of AVP-dependent Na+ reabsorption by the CCD, and they introduce another signalling system as a candidate in the aetiology of low-renin, salt-dependent hypertension.     

Low sodium intake induces an increase in renal monoamine oxidase activity in the rat. Involvement of an angiotensin II dependent mechanism

AIMS: The interplay between natriuretic dopamine and antinatriuretic angiotensin II represents an important mechanism for the regulation of renal sodium and water excretion. Monoamine oxidase is the main metabolizing pathway for dopamine in the renal cortex. In this study, we have analysed the effect of low sodium feeding and AT1 receptor blockade on renal dopamine metabolism by monoamine oxidase. METHODS: Four groups of rats were studied: 1, normal salt diet (NS); 2, low salt diet (LS); 3, NS receiving Losartan (Los, specific AT1 receptor antagonist, 20 mg kg(-1) bwt day(-1), NS + Los); 4, LS receiving Los (LS + Los). RESULTS: Urinary dopamine excretion was lower in LS than in NS rats (543 +/- 32 vs. 680 +/- 34 ng day(-1) 100 g(-1) bwt, P < 0.05). When treated with Los, DOPAC excretion and urinary DOPAC/dopamine ratio fell significantly in the LS + Los group as compared with the LS group (1199 +/- 328 vs. 3081 +/- 681 ng day(-1) 100 g(-1) bwt and 1.90 +/- 0.5 vs. 5.7 +/- 1.2, respectively, both P < 0.02). Losartan increased hydroelectrolyte excretion in the LS group. No changes were found in the NS + Los group. Aromatic L-amino acid decarboxylase activity in cortex was similar in NS and LS rats. Instead, monoamine oxidase activity was higher in cortical homogenates from LS rats (in nmol mg tissue(-1) h(-1): NS 7.66 +/- 0.52; LS 9.82 +/- 0.59, P < 0.05) and this difference was abolished in LS + Los rats (7.34 +/- 0.49 nmol mg tissue(-1) h(-1), P < 0.01, vs. LS). CONCLUSIONS: We have concluded that low levels of dopamine in the urine of LS rats are because of an increase in the activity of renal monoamine oxidase and that angiotensin II mediates this increase through stimulation of AT1 receptors.     

Central nitric oxide blocks vasopressin, oxytocin and atrial natriuretic peptide release and antidiuretic and natriuretic responses induced by central angiotensin II in conscious rats

The presence of nitric oxide synthase (NOS), the enzyme that catalyses the formation of nitric oxide (NO), in the circumventricular organs and magnocellular neurones suggests an important role of NO in the modulation of vasopressin (AVP) and oxytocin (OT) release. Intracerebroventricular (I.C.V.) injection of angiotensin II (Ang II) stimulates the release of AVP, OT and atrial natriuretic peptide (ANP), with the resultant antidiuretic and natriuretic effects. This study investigated the interaction between nitrergic and angiotensinergic pathways on the release of AVP, OT and ANP and on urinary volume and sodium excretion in water-loaded rats. Unanaesthetized, freely moving, male Wistar rats received two water loads followed by an injection into the lateral ventricle of an inhibitor of NOS (L-NAME), a NO donor [3-morpholinylsydnoneimine chloride (SIN-1) or S-nitroso-N-acetyl penicillamine (SNAP)] or vehicle (isotonic saline) and, 20 min after, they received a second I.C.V. injection of Ang II or vehicle. Injections of L-NAME or Ang II produced an increase in plasma levels of AVP, OT and ANP, a reduction in urinary volume and an increase in sodium excretion. Pretreatment with L-NAME enhanced the Ang II-induced increase in AVP, OT and ANP release, as well as the antidiuresis and natriuresis. Injection of SIN-1 or SNAP did not modify hormonal plasma levels and urinary parameters. In contrast SNAP blocked the AVP, OT and ANP release, as well as antidiuretic and natriuretic responses induced by ANG-II. Thus, the central nitrergic system can act to inhibit AVP, OT and ANP secretion and the antidiuretic and natriuretic effects in response to Ang II.     

Intracellular sodium modulates the state of protein kinase C phosphorylation of rat proximal tubule Na+,K+‐ATPase

The natriuretic hormone dopamine and the antinatriuretic hormone noradrenaline, acting on α‐adrenergic receptors, have been shown to bidirectionally modulate the activity of renal tubular Na⁺,K⁺‐adenosine triphosphate (ATPase). Here we have examined whether intracellular sodium concentration influences the effects of these bidirectional forces on the state of phosphorylation of Na⁺,K⁺‐ATPase. Proximal tubules dissected from rat kidney were incubated with dopamine or the α‐adrenergic agonist, oxymetazoline, and transiently permeabilized in a medium where sodium concentration ranged between 5 and 70 mM . The variations of sodium concentration in the medium had a proportional effect on intracellular sodium. Dopamine and protein kinase C (PKC) phosphorylate the catalytic subunit of rat Na⁺,K⁺‐ATPase on the Ser23 residue. The level of PKC induced Na⁺,K⁺‐ATPase phosphorylation was determined using an antibody that only recognizes Na⁺,K⁺‐ATPase, which is not phosphorylated on its PKC site. Under basal conditions Na⁺,K⁺‐ATPase was predominantly in its phosphorylated state. When intracellular sodium was increased, Na⁺,K⁺‐ATPase was predominantly in its dephosphorylated state. Phosphorylation of Na⁺,K⁺‐ATPase by dopamine was most pronounced when intracellular sodium was high, and dephosphorylation by oxymetazoline was most pronounced when intracellular sodium was low. The oxymetazoline effect was mimicked by the calcium ionophore A23187. An inhibitor of the calcium‐dependent protein phosphatase, calcineurin, increased the state of Na⁺,K⁺‐ATPase phosphorylation. The results imply that phosphorylation of renal Na⁺,K⁺‐ATPase activity is modulated by the level of intracellular sodium and that this effect involves PKC and calcium signalling pathways. The findings may have implication for the regulation of salt excretion and sodium homeostasis.     

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.     

Effects of brain natriuretic peptide on hemodynamics and renal function in dogs

A new natriuretic peptide has been found in the porcine brain and termed brain natriuretic peptide (BNP). To examine the effects of BNP on the cardiovascular system and kidney as compared with alpha-hANP (ANP), BNP, and ANP (33, 167, 667 pmol/kg) were intravenously administered to anesthetized dogs. BNP dose-dependently decreased arterial pressure and left atrial pressure and dose-dependently increased heart rate, cardiac output, renal blood flow, urine volume, and sodium excretion. These effects were not significantly different from the effects of respective doses of ANP. To eliminate the possibility that these results were confounded by opposing actions of the baroreflex system, we performed additional experiments following sinoaortic denervation and vagotomy. These results also demonstrated no differences between the effects of BNP and ANP on the measured variables. Finally, we determined that the pharmacokinetics of exogenously injected BNP and ANP are indistinguishable. These findings lead to the possibility that BNP physiologically works in the body in the same manner as ANP.     

The natriuretic response to a dopamine DA1 agonist requires endogenous activation of dopamine DA2 receptors

Dopamine produced in the kidney acts as a natriuretic hormone by inhibiting tubular Na⁺, K⁺-ATPase activity. Previous in vitro studies have shown that Na⁺, K⁺-ATPase activity in the proximal tubule is inhibited by a synergistic action of dopamine 1 (DA₁) and dopamine 2 (DA₂) receptors. This in vivo study, performed on rats, investigates whether the natriuretic response to DA requires a synergistic action of DA₁ and DA₂ receptors. The DA₁ agonist, fenoldopam, significantly increased urinary sodium excretion, but there was no increase in sodium excretion when a DA₁ agonist was given together with a DA₂ antagonist. Neither DA₁ nor DA₂ antagonists had any influence on sodium excretion. The natriuretic response to fenoldopam was also significantly attenuated after the administration of benserazide, which inhibits aromatic acid decarboxylase and thereby suppresses the endogenous production of dopamine. In conclusion, the natriuretic effect of dopamine depends on the activation of both DA₁ and DA₂ receptors. The DA₂ receptor appears to be constitutively activated by endogenous dopamine.     

Development and application of a urodilatin (CDD/ANP-95#x2013;126)-specific radioimmunoassay

Urodilatin, a renal natriuretic peptide that is an analogue to circulating atrial natriuretic peptide [-ANP (99-126)], is measurable with a highly specific and sensitive radioimmunoassay. While most ANP antibodies cannot distinguish between urodilatin and other ANP analogues, the polyclonal urodilatin antibody specifically measures human urodilatin without any cross-reactivity to other ANP analogues. Urodilatin is not detected in blood from healthy volunteers nor from cardiac patients. Urinary urodilatin accounts for only a part of total urinary ANP immunoreactivity. Urodilatin excretion closely parallels sodium excretion in response to an acute volume load while changes in urinary immunoreactive ANP excretion do not reflect this renal response. We conclude that specific urodilatin assays are required to explore further the physiological role of the renal natriuretic peptide.     

The lack of receptors for atrial natriuretic peptides on human monocytes prevents a rise of cGMP and induction of tumor necrosis factor-alpha synthesis.

Freshly harvested human monocytes were shown to produce tumor necrosis factor-alpha (TNF-alpha) in response to exogenously added or sodium nitroprusside-generated cGMP. In contrast, atrial natriuretic peptide (ANP) that acts by elevating cGMP in a variety of cells, was incapable of inducing TNF-alpha synthesis. This failure was due to a lack of ANP receptors and thus, to the inability of ANP to raise cGMP in human monocytes.     

Effects of oxytocin in normal man during low and high sodium diets

AIM: We tested the hypothesis that oxytocin in normal man causes natriuresis by means of nitric oxide and/or atrial natriuretic peptide. METHODS: Normal male subjects were investigated after 4 days of sodium controlled diets (30 mmol sodium chloride day(-1), n = 8 or 230 mmol sodium chloride day(-1), n = 6). Oxytocin was infused intravenously (1 pmol kg(-1) min(-1) for 240 min). RESULTS: Mean arterial blood pressure, heart rate and glomerular filtration rate by clearance of chromium-labelled ethylenediaminetetraacetate remained stable. Plasma oxytocin increased from 2 to 3 pg mL(-1) to around 50 pg mL(-1). Oxytocin decreased urine flow (4.2 +/- 0.2--0.75 +/- 0.11 and 4.6 +/- 1.3-1.4 +/- 0.6 mL min(-1), low- and high-salt diet, respectively). During low-salt conditions, oxytocin reduced sodium and potassium excretion (11 +/- 2--4 +/- 2 and 93 +/- 19--42 +/- 3 micromol min(-1), respectively). Plasma renin, angiotensin II, aldosterone and renal excretion of metabolites of nitric oxide (nitrate and nitrite) all decreased. Plasma atrial natriuretic peptide and cyclic guanosine monophosphate were unchanged. A similar pattern was obtained during high-salt conditions but in this case the antinatriuresis was not different from that occurring during the corresponding time control series. CONCLUSIONS: The data reject the hypothesis. In contrast, we found significant antinatriuretic, antikaliuretic and antidiuretic effects, which were not mediated by the renin-angiotensin-aldosterone system, atrial natriuretic peptide, systemic haemodynamics, or processes increasing urinary excretion of metabolites of nitric oxide. The natriuretic effect of oxytocin found in laboratory animals is species-specific.     

Renal and cardiovascular effects of atrial natriuretic peptide in Wistar-Kyoto and spontaneously hypertensive rats during a chronic salt loading

Spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats were maintained on tap water or 1.5% NaCl for 3 weeks. During the high sodium regime 24-h urinary sodium excretion increased 10-fold and the basal blood pressure increased in the SHR. After 3 weeks the rats received arterial (carotid artery), venous and bladder catheters (suprapubic). Saline was infused continuously and in conscious rats atrial natriuretic peptide (alpha-hANP) was administered as bolus injections (8 and 16 nmol kg-1) and the blood pressure and heart rate and the urinary excretions of sodium, potassium (flame photometry), noradrenaline and dopamine (HPLC) were followed at 5-min intervals. The administration of ANP caused a short-lasting blood pressure reduction, tachycardia, diuresis and increased urinary excretions of sodium, potassium, noradrenaline and dopamine. The blood pressure responses to ANP did not differ between the rat strains, irrespective of the diet. The natriuresis and diuresis to ANP was reduced in animals on a high sodium diet, especially in the SHR. This may be interpreted as a down-regulation of target organ responsiveness to ANP during a high sodium diet and the inappropriately large decrease in the responsiveness that was observed in the SHR may be related to increase in blood pressure during the high sodium diet.     

Different renal effects of two inhibitors of catechol-O-methylation in the rat: Entacapone and CGP 28014

Dopamine is a natriuretic hormone that is abundantly synthesized in the kidney and is involved in sodium homeostasis. It is metabolized by monoamine oxidase (MAO) and catechol-O-methyl transferase (COMT) to form 3-methoxytyramine and dihydroxyphenylacetic acid (DOPAC) and finally homovanillic acid (HVA). In order to investigate whether dopamine metabolism is involved in renal sodium regulation, we tested the renal effects of the nitrocatechol entacapone (COMT inhibitor), in comparison with those of the pyridine derivative CGP 28014, in the anaesthetized rat. Entacapone injection resulted in a more than 5-fold increase in sodium excretion, while the renal excretion of dopamine only transiently increased by 20%. DOPAC excretion showed a more than 2-fold increase which persisted throughout the study. Pretreatment with the selective dopamine DA₁-receptor antagonist SCH23390 reduced the entacapone-induced natriuretic response by 69%. Glomerular filtration rate (GFR) and mean arterial blood pressure (MAP) remained unchanged. Injection of CGP 28014 did not produce a natriuretic response; nevertheless, both dopamine and DOPAC excretion increased by 78% and more than 2-fold, respectively. GFR and MAP remained unchanged. In conclusion, COMT inhibition using entacapone results in a mainly DA₁ receptor mediated natriuresis involving inhibition of tubular transport processes, supporting a role for dopamine metabolism in sodium homeostasis. Although CGP 28014 increases the renal excretion of both dopamine and DOPAC it does not affect renal sodium handling indicating a different mechanism of action.     

C-type natriuretic peptide does not affect plasma and urinary adrenomedullin in man.

To investigate whether C-type natriuretic peptide (CNP) at pathophysiological plasma levels stimulates the release of adrenomedullin (ADM) in man, six healthy subjects (three men and three women, mean age 35 +/- 3 years, range 33-40 years) received an intravenous infusion of synthetic human CNP-22 (2 pmol kg-1 min for 2 h), in a single-blind, placebo-controlled, random order, cross-over study, with measurements of the plasma levels of cyclic guanosine monophosphate (cGMP), ADM, renin and atrial natriuretic peptide (ANP), arterial pressure, heart rate, renal blood flow (para-aminohippurate clearance), glomerular filtration rate (creatinine clearance), and the urinary excretion rates of cGMP, ADM and sodium. Infusion of CNP induced increases in its own levels (from 1.17 +/- 0.11 up to 21.13 +/- 1.41 pmol l-1) without modifying the plasma levels of cGMP, ADM, renin and ANP, the urinary excretion rate of ADM and cGMP, renal haemodynamics and sodium excretion. These data indicate that circulating CNP is not involved in the regulation of ADM release, renal haemodynamics and sodium excretion in man.     

钠摄入量对充血性心衰大鼠血浆及心肌Ang Ⅱ、Ald和ANP水平的影响

观察严格限钠或适量补钠对充血性心衰(CHF)大鼠血钠及血浆和心肌组织中血管紧张素Ⅱ(AngⅡ)、醛固酮(Ald)和心钠素(ANP)水平的影响。结果表明：限钠使血钠进一步降低(P＜ 0.05), 血浆AngⅡ、Ald、ANP水平进一步升高(均 P＜ 0.01),尿钠、尿量显著减少,心衰加重;补钠则使血钠恢复正常,血浆AngⅡ和Ald降至正常,ANP仍保持较高水平,尿钠、尿量显著增加,心衰缓解。提示：充血性心衰时,适当补钠可促使RAAS与ANPS两大激素系统之间的活性恢复平衡、促进排钠利尿、心衰缓解。     

Urinary dopamine excretion in healthy volunteers: effect of sodium diet and acute water load

The present study was designed to investigate, in human subjects, urinary dopamine excretion under different conditions of sodium and water homeostasis. In a cross-over trial, ten healthy volunteers were subjected to low-salt (LS; dietary salt restriction, sodium chloride (NaCl) intake <5 g per day), normal-salt (NS; normal food ad libitum), and high-salt (HS; normal food plus NaCl 100 mg/kg per day) regimens for 8 days in a randomized order. On day 7, urine was collected for 24 h. The variations in urinary sodium excretion reflected the dietary salt intake (LS: 16.3+/-4.7; NS: 144.1+/-18.2; HS: 221.9+/-12.9 mmol 24 h(-1) 1.73 m(-2)), but were not accompanied by significant changes in urinary dopamine excretion. On day 8, clearance studies showed that an acute oral water load of 1500 ml did not alter glomerular filtration rate or renal plasma flow but significantly increased urinary flow rate without affecting dopamine excretion. Assuming that excreted dopamine is not metabolized or reabsorbed during the tubular passage, both the unchanged urinary dopamine output in spite of 14-fold variations in sodium excretion and its independence of an acute water load argue against the hypothesis that dopamine in the tubular lumen acts as a natriuretic and/or diuretic factor in humans.