Changes in renal hemodynamics and sodium excretion during saline infusion in lambs.

The renal response to a progressive isotonic extracellular volume (ECV) expansion was studied in 13 lambs of two age groups (5-28 days and 48-57 days). Changes in renal hemodynamics induced by the ECV expansion were followed. Intrarenal blood flow was determined by the microsphere method. For determination of the glomerular filtration rate (GFR) standard clearance techniques were used. Recordings were made during control conditions and when normal saline had been infused in amounts up to 4.5% of the body weight. During the infusion there was an increase in sodium excretion both in absolute values and in relationship to GFR. The increase was, however, much less pronounced in the younger lambs. The GFR did not change significantly during saline infusion. The cortical blood flow increased only in the older lambs. As a consequence the quotient between GFR and cortical blood flow decreased in the older lambs. The possibility of a causal relationship between the fall in filtration fraction so obtained and the more pronounced natriuretic response in the older lambs is discussed. The inner to outer cortical blood flow ratio increased more in the younger lambs during saline infusion. The functional significance of an age related blood flow redistribution is, however, not clear.     

Role of Nitric Oxide and Renal Nerves in the Renal Responses to Acute Volume Expansion in Anaesthetized Rats

An investigation was undertaken into the potential role of nitric oxide (NO) and its interaction with renal sympathetic nerves in mediating renal responses to acute saline volume expansion (VE). Groups of anaesthetized Wistar rats with innervated and denervated kidneys were subjected to VE, 0.25 % body wt min-1 for 40 min, in the presence and absence of nitric oxide synthase (NOS) inhibitors, NG-nitro-L-arginine-methyl-ester (L-NAME, non-selective), aminoguanidine (AG, relatively selective for inducible NOS (iNOS)), and 7-nitroindazole (7-NI, relatively selective for neuronal NOS (nNOS)). Pretreatment with L-NAME or AG enhanced the cumulative sodium excretion (CuU(Na)V) after 40 min VE in the innervated kidneys by 27 and 23 % (both P < 0.001), respectively, compared to the untreated control group, whereas they were without effect in the denervated kidneys. Cumulative urine flow (CuUV) after VE in L-NAME- and AG-treated groups was enhanced in both kidneys, by some 17-21 % in the denervated (P < 0.01) and 37-39 % in the innervated kidneys (P < 0.001) by comparison with the corresponding untreated controls. 7-NI had no effect on CuUV, but reduced CuU(Na)V in the denervated kidneys by 25 % (P < 0.01) when compared to the control group. The results suggested that NO, possibly generated by endothelial NOS (eNOS) and iNOS, was a contributory factor in mediating the renal response to VE. There appeared to be a tonic inhibitory action of NO on water excretion which was renal nerve independent, whereas its impact on sodium handling appeared to be dependent upon a background level of renal nerve activity. Experimental Physiology (2001) 86.1, 47-54.     

Renal excretion of prostaglandin metabolites, arginine vasopressin, and sodium during endotoxin and endogenous pyrogen induced fever in the goat

Responses to intravenous injections of an endotoxin (E. coli-lipopolysaccharide, 1 microgram/kg b.wt.) and endogenous pyrogen were studied in euhydrated and hyperhydrated goats. The biphasic febrile response to the endotoxin was associated with a pronounced increase in the renal excretion of measured prostaglandin (PG) metabolites (11-ketotetranor PGF metabolites). This increase was time-correlated with the elevation of the rectal temperature, and (in hyperhydrated animals) with an inhibition of the water diuresis and an increase in renal excretion of arginine vasopressin (AVP). Other effects of the endotoxin were an immediate depression of renal Na and K excretion followed by the development of pronounced natriuresis, and a reduction of plasma Fe and Zn concentrations. The appearance of the febrile reactions (peripheral vasoconstriction and shivering) was accompanied by miosis. The maximum elevation of the rectal temperature was significantly greater during euhydration than during hyperhydration. Also endogenous pyrogen elicited miosis concomitant with febrile reactions, and an elevation of the renal excretion of PG metabolites which was closely correlated in time with the monophasic febrile response, and (during hyperhydration) with temporary inhibition of the water diuresis and an increase in the renal AVP excretion. However, the responses were much weaker than the corresponding endotoxin effects. No appreciable changes in renal excretion of Na and K were observed in response to the endogenous pyrogen. It is concluded that the observed effects on renal cation excretion were manifestations of direct endotoxin influences on kidney function.(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.     

Atrial natriuretic factor, urinary catechol compounds and electrolyte excretion in rats during normal hydration and isotonic volume expansion. Influence of dopamine receptor blockade

To investigate the influence of acute isotonic volume expansion (VE) on the plasma concentration of atrial natriuretic factor (ANF), the excretion of catechol compounds and electrolytes and the whole kidney glomerular filtration rate (GFR), these variables were measured before and during 60 min of VE (2% of body weight per hour). Atrial natriuretic factor was measured at the end of the experiment. In a control group (n = 7) without volume expansion, plasma ANF was 58 +/- 4 pg ml-1. The excretion of sodium, dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), noradrenaline (NA) and GFR did not change during the control study. In VE animals (n = 7) plasma ANF was 82 +/- 7 pg ml-1, significantly higher than in the control group. Sodium excretion increased more than 17-fold. The excretion of the DA increased by 38% and that of DOPAC by 30%. Noradrenaline excretion remained unchanged while GFR increased by 20%. In haloperidol-pretreated animals subjected to VE (n = 7), plasma ANF was 81 +/- 8 pg ml-1 during VE, significantly higher than in the control animals. Although the sodium excretion increased more than ninefold in this group during VE, this increase was only 55% of that in the VE group not given haloperidol. The DA and DOPAC excretion was increased by haloperidol, indicating a feedback effect of receptor blockade. DOPAC excretion was not increased further by VE, but the excretion of DA increased by 15% and GFR increased by 19%.(ABSTRACT TRUNCATED AT 250 WORDS)     

CNS-induced natriuresis during dopamine receptor blockade. Further support for the existence of, at least, two separate natriuretic hormonal systems

Intracerebroventricular (ICV) stimulation with hypertonic sodium chloride solutions has previously shown indications to stimulate the release of a blood-borne natriuretic factor. Sodium excretion in this situation increases in the order of 10-20 times. Acute isotonic volume expansion has shown to be a potent stimulus for endogenous release of the atrial natriuretic factor (ANF). It has also been demonstrated that the natriuretic response to both volume expansion and exogenously applied ANF can be attenuated by the dopamine receptor blocker haloperidol. The present study was performed to investigate if the natriuretic response to ICV stimulation also could be attenuated with haloperidol, thus indicating similar effector mechanisms as for ANF. A first group of anaesthetized animals was, therefore, pre-treated with haloperidol (H) and then ICV stimulated (H-ICV). A second group of animals was subjected to acute isotonic volume expansion (VE, 2% b.w.h.-1) to evoke the documented ANF release. In a third group of animals pre-treatment with haloperidol was followed by volume expansion (H-VE). In the H-ICV group there was a more than 30-fold increase in sodium excretion, due to an increase both in urine flow rate (more than sixfold) and in the urinary concentration of sodium (more than fourfold). Potassium excretion increased more than eightfold, urine osmolality was unchanged, and blood pressure increased by 7%. In the VE group sodium excretion increased more than 18-fold, consequent to large increases in urine flow rate (more than 23-fold), while the urinary concentration of sodium tended to decrease. Potassium excretion increased more than threefold, urine osmolality decreased by 88%, and blood pressure was unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)     

Arginine vasopressin excretion in response to volume expansion in the healthy human,and in patients with glomerulonephritis

The urinary excretion of arginine vasopressin (AVP) was studied during volume expansion (VE) in nine healthy normotensive individuals and 14 patients with active IgA glomerulonephritis (GN). The studies were started after 17–18 h of food and fluid deprivation (hydropenia, HP) and VE was induced by a continuous infusion of Ringer solution up to an amount corresponding to 3% of the body weight. The clearance of inulin and PAH, urine osmolality and urinary excretion of sodium and AVP were determined. The AVP excretion decreased in response to VE in the healthy individuals, both when related to GFR (from 129+ 17 pg min ‘ 100 ml ’ GFR during HP to 65 ± 9 after 3% VE, P < 0.01)andtobody surface area (BSA) (from 134 ± 22 pg min“¹ 1.73 m^-2 BSA to 75 ±11, P < 0.05). In the patients with IgA GN, who had normal blood pressure and normal GFR, the AVP excretion tended to decrease, but the change was not significant (0.05 < P < 0. 1). The patients with hypertension but essentially normal GFR, and those with hypertension and markedly decreased GFR did not change their renal excretion of AVP in response to VE. If related to the GFR, the latter patients had a markedly increased AVP excretion.     

Effect of isotonic volume expansion on proximal tubular reabsorption of Na and fluid in the developing rat kidney1

Young rats (aged 22–24 days) and adult rats (aged 40–42 days) were studied during hydropenia (HP) and during volume expansion (VE) in order to clarify the role of the proximal tubule of the immature kidney in the blunted natriuretic response seen in young mammals during VE. The position of the last accessible site for micropuncture of the proximal tubular segment was determined. The disadvantages of using lissamine green as a marker of different tubular segments were investigated. Tubular function was ascertained by micropuncture of superficial proximal nephrons. Measurements of tubular length were made from latex casts of the proximal tubule. No side-effects of lissamine green were detected, when small quantities were used (20–30 μl) and at least 20 min elapsed between the infusions of the dye and tubular samplings. The last accessible proximal tubule available for micropunction was found to be similarly located in young and adult rats. Fractional reabsorption during HP remained constant during development. An equivalent degree of VE induced an increase in tubular load in both age groups, but it was more marked among younger rats. Absolute proximal reabsorption in both young and old rats in HP paralleled that of the tubular load. Fractional reabsorption, however, decreased slightly during VE but to the same extent in both age groups. This indicates a great flexibility in the immature proximal tubule under various tubular loads although it had been thought that this part of the nephron was in the later stages of development. The results imply that the proximal tubule does not create the blunted sodium response in the immature kidney during VE.     

Effect of Arterial Blood Pressure Reduction on Renal Hemodynamics in the Developing Lamb

Aperia , A. and P. Herin . Effect of arterial blood pressure reduction on renal hernodynamics in the developing lamb. Acta physiol. scand. 1976. 98. 387–394. The relationship between pressure and flow in the kidney has been examined in 2–9 and 31–48 day old lambs. Renal blood flow (RBF), determined by the microsphere technique, and glomerular filtration rate (GFR) were first studied under control conditions. The abdominal aorta was then constricted above the renal arteries until the pressure ranged between 60 and 70 mmHg, i.e. just below the normal auto-regulatory range, and the hemodynamic recordings were repeated. During control conditions the arterial pressure was lower in the younger (93 mmHg) than in the older lambs (107 mmHg). During aortic constriction total RBF and GFR were reduced. In both age groups GFR was reduced out of proportion to RBF. The sodium excretion fell around 60% in both age groups. The fall in perfusion pressure resulted in a more pronounced blood flow reduction to the outer than to the inner cortical glomerular capillaries. This pressure-induced blood flow redistribution was found in both age groups. The consequences of the pronounced effect of reducing the perfusion pressure to 60–65 mmHg for the young lambs with their basally low arterial blood pressure are discussed.     

Atrial natriuretic peptide attenuates pressor but enhances natriuretic responses to angiotensin II in pregnant conscious goats

This study was designed to examine the actions of ANP in acute, ANGII-mediated hypertension during pregnancy. Effects on blood pressure, blood volume, and renal Na and K excretion were evaluated in conscious goats (n= 6). ANP (2 μrg min^-1), ANGII (0.5 μg min^-1), or ANGII + ANP (doses the same as for each peptide alone) was infused intravenously for 60 min. The pressor response to ANGII was reduced in pregnant goats. This reduction was seen in systolic, but not in diastolic pressure. ANP decreased pressure by 5–10 mmHg both in pregnancy and in non-pregnancy. When ANGII + ANP was infused, blood pressure initially rose as with ANGII but then declined. ANP suppressed only the elevated systolic pressure. Plasma protein concentration and haematocrit was reduced by ANGII but increased by ANP alone or together with ANGII, thereby implying fluid shift into the vasculature by ANGII and opposite movement by ANP. ANGII increased renal Na excretion to 1500 μmol min^-1in non-pregnancy, but only to half of that in pregnancy. ANP alone caused small natriuresis, but enhanced ANGII-induced natriuresis to near 3000 μmol min^-1in both non-pregnant and pregnant goats. In summary, ANP further attenuated the blunted blood-pressure rise due to ANGII in pregnant goats, and reduced plasma volume, but enhanced renal Na excretion as in non-pregnant goats. This implies that with the present combination ANP and ANGII caused a near maximal natriuretic response that was not modified by the systemic cardiovascular changes occurring in pregnant goats.     

Compensatory adaptation of sodium and bicarbonate excretion: effect of diuretics.

Complete clamping of the contralateral kidney results in a rapid and significant increase in the fractional excretion of Na, K, and bicarbonate by the remaining kidney during bicarbonate loading. Similar studies were performed in dogs after administration of diuretics with different major sites of action to localize the adaptive excretory response to acute reduction in renal mass. Volume expansion was carefully avoided. In experiments with the loop inhibitor, furosemide, contralateral kidney clamping rapidly and significantly increased fractional excretion of Na and bicarbonate. A more delayed and smaller response was observed in dogs given hydrochlorothiazide. Acetazolamide, a potent inhibitor of proximal Na bicarbonate reabsorption, completely blocked the excretory response to contralateral kidney clamping. The enhanced response with furosemide and its blockade with acetazolamide indicates a proximal site of adaptation to acute contralateral kidney exclusion. The overall natriuretic response depends on the level of inhibition of loop reabsorption.     

Atrial natriuretic hormones — Thirty years after the discovery of atrial volume receptors

Summary Twenty-five years after the discoveries of the existence of atrial granules and of volume receptors in the heart atria the search for natriuretic hormones has led to the isolation and identification of the atrial natriuretic factors (ANF) now considered as a hormonal system. These peptides are probably synthesized and stored in the Golgi apparatus of cardiac myocytes and are released in response to atrial wall stretch following acute plasma volume expansion and increased central blood volume, e.g., during head-out water immersion, in arterial hypertension, or increased left and/or right atrial pressure in cardiac failure, but also possibly in response to increased frequency of myocardial contractions, e.g. in paroxysmal tachycardia. The mechanisms of the renal action of these potent natriuretic hormones are not yet precisely known. Increased GFR may contribute to the initial rise in urinary sodium excretion and increased renal medullary blood flow to the later phase of natriuresis. The proximal tubule, the thin descending and the ascending limb of Henle's loop and especially the medullary collecting tubule were so far incriminated as tubular sites of action of ANF. Finally, recycling of sodium in medullary tissue and secretion of sodium via back-flux from the interstitium into the medullary collecting tubule are postulated to result in the hypernatric urine observed after ANF administration. Direct suppression of the secretion of renin, aldosterone, vasopressin, and vasopressin-stimulated cAMP synthesis may also contribute to its diuretic, natriuretic, and antihypertensive effects. The renal hemodynamic and tubular as well as the adrenal and systemic vascular effects are related to enhanced cGMP synthesis in medium-sized arterial vessels, in glomeruli and specific tubular segments, and in adrenal tissue, and may be calcium dependent. Specific ANF-binding sites were detected in these target organs. Although increased ANF release was observed in response to atrial distension in various disease states, which may contribute to renal sodium elimination in human hypertension and congestive heart failure, further studies are needed to identify its precise physiological and pathophysiological significance.Abbreviations ACTH Adrenocorticotropic hormone - ANF Atrial natriuretic factor - AVP Arginine vasopressin - cAMP Cyclic adenosine monophosphate - cGMP Cyclic guanosine monophosphate - d-DAVP d-Desamino arginine vasopressin - DOCA Deoxycorticosterone acetate - ECFV Extracellular fluid volume - GFR Glomerular filtration rate - PAH Paraaminohippurate - PG Prostaglandin - PRA Plasma renin activity - RBF Renal blood flow - SNGFR Single nephron GFR Dedicated to Prof. Dr. F. Krück on the occasion of his 65th birthday     

Atrial natriuretic peptide attenuates pressor but enhances natriuretic responses to angiotensin II in pregnant conscious goats.

This study was designed to examine the actions of ANP in acute, ANGII-mediated hypertension during pregnancy. Effects on blood pressure, blood volume, and renal Na and K excretion were evaluated in conscious goats (n = 6). ANP (2 micrograms min-1), ANGII (0.5 microgram min-1), or ANGII+ANP (doses the same as for each peptide alone) was infused intravenously for 60 min. The pressor response to ANGII was reduced in pregnant goats. This reduction was seen in systolic, but not in diastolic pressure. ANP decreased pressure by 5-10 mmHg both in pregnancy and in non-pregnancy. When ANGII+ANP was infused, blood pressure initially rose as with ANGII but then declined. ANP suppressed only the elevated systolic pressure. Plasma protein concentration and haematocrit was reduced by ANGII but increased by ANP alone or together with ANGII, thereby implying fluid shift into the vasculature by ANGII and opposite movement by ANP. ANGII increased renal Na excretion to 1500 mumol min-1 in non-pregnancy, but only to half of that in pregnancy. ANP alone caused small natriuresis, but enhanced ANGII-induced natriuresis to near 3000 mumol min-1 in both non-pregnant and pregnant goats. In summary, ANP further attenuated the blunted blood-pressure rise due to ANGII in pregnant goats, and reduced plasma volume, but enhanced renal Na excretion as in non-pregnant goats. This implies that with the present combination ANP and ANGII caused a near maximal natriuretic response that was not modified by the systemic cardiovascular changes occurring in pregnant goats.     

Influence of ruminal water‐loading on renal sodium excretion and water intake following feeding in sheep

We investigated the effect of ruminal water loading before feeding on the natriuretic and drinking responses that follow feeding. Six sheep fed 800 g of chaff drank 1360 ± 150 mL during the 5 h immediately following feeding and increased renal Na excretion. Plasma Na concentration increased by 4 mmol L^–1 and plasma osmolality by 9 mosmol kg^–1 within 1.5 h and remained elevated. A rumen load of water administered before feeding prevented the increases in plasma Na and osmolality without affecting feeding. The natriuresis, water drinking and vasopressin secretion in response to feeding were abolished. Total sodium excreted during the experiment was halved in water‐loaded animals compared with untreated animals (30.4 ± 2.1 mmol^–1 cf. 63.8 ± 2.9 mmol^–1; P < 0.01). Ruminal loading with isotonic saline caused a 33% reduction in postprandial drinking, however, reducing cerebrospinal fluid NaCl concentration abolished postprandial drinking and natriuresis. Intravenous infusion of isotonic dextran appeared to delay the onset of water intake without changing the total volume of water drunk, suggesting a role of plasma volume in initiating drinking. We conclude from the data that central osmoregulatory mechanisms that include increased sodium excretion as well as thirst and vasopressin release are activated following food intake by sheep.     

Renal nerve blunts natriuretic and diuretic response to atrial natriuretic peptide in conscious rabbits

The contribution of the renal nerve to the natriuretic and diuretic responses to rat atrial natriuretic peptide (rAMP) was investigated in conscious rabbits with unilateral renal denervation. Renal nerve activity (RNA) was measured at the contralateral innervated kidney. Catheters were bilaterally implanted into the ureters. Urine samples were collected from each kidney by gravity drainage at 10-min clearance intervals. In rabbits with all baroreflexes intact, infusion of rANP at 0.3 micrograms/(kg.min) for 30 min decreased mean arterial pressure by 8 +/- 4 mmHg and increased RNA by 53 +/- 13%. After sinoaortic baroreceptor denervation (SAD), hypotensive response to infusion of rANP was greater than that in intact rabbits, while RNA did not change. After SAD plus vagotomy, infusion of rANP lowered mean arterial pressure by 21 +/- 4 mmHg and RNA by 19 +/- 6%. In the denervated kidney, infusion of rANP increased Na+ excretion by 16.1 +/- 4.5 from 3.5 +/- 1.0 muEq/min and water excretion by 0.17 +/- 0.05 from 0.08 +/- 0.02 ml/min. In the contralateral innervated kidney, infusion of rANP increased the amount of Na+ and water excretion by 4.5 +/- 3.2 muEq/min and 0.07 +/- 0.04 ml/min, which were significantly less than those in the denervated kidney. These results indicate that infusion of rANP increases RNA, due to baroreceptor reflexes, and that this increase in RNA blunts natriuretic and diuretic action of rANP.     

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.     

Relationship between individual ventilatory response and acute renal water excretion at high altitude

We tested the hypothesis that the individual ventilatory adaptation to high altitude (HA, 5050 m) may influence renal water excretion in response to water loading. In 8 healthy humans (33+/-4 S.D. years) we studied, at sea level (SL) and at HA, resting ventilation (VE), arterial oxygen saturation (SpO2), urinary output after water loading (WL, 20 mL/kg), and total body water (TBW). Ventilatory response to HA was defined as the difference in resting VE over SpO2 (DeltaVE/DeltaSpO2) from SL to HA. At HA, a significant increase in urinary volume after the first hour from WL (%WLt0-60) was observed. Significant correlations were found between DeltaVE/DeltaSpO2 versus %WLt0-60 at HA and versus changes in TBW, from SL to HA. In conclusion, in healthy subjects the ventilatory response to HA influences water balance and correlates with kidney response to WL. A higher ventilatory response at HA, allowing a more efficient water renal handling, is likely to be a protective mechanisms from altitude illness.     

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.     

Atrial natriuretic factor,urinary catechol compounds and electrolyte excretion in rats during normal hydration and isotonic volume expansion. Influence of dopamine receptor blockade.

To investigate the influence of acute isotonic volume expansion (VE) on the plasma concentration of atrial natriuretic factor (ANF), the excretion of catechol compounds and electrolytes and the whole kidney glomerular filtration rate (GFR), these variables were measured before and during 60 min of VE (2% of body weight per hour). Atrial natriuretic factor was measured at the end of the experiment. In a control group (n= 7) without volume expansion, plasma ANF was 58 ± 4 pg ml^-1. The excretion of sodium, dopamine (DA), 3 ,4–dihydroxyphenylacetic acid (DOPAC), noradrenaline (NA) and GFR did not change during the control study. In VE animals (n= 7) plasma ANF was 82 ± 7pg ml^-1, significantly higher than in the control group. Sodium excretion increased more than 17–fold. The excretion of the DA increased by 38% and that of DOPAC by 30%. Noradrenaline excretion remained unchanged while GFR increased by 20%. In haloperidol-pretreated animals subjected to VE (n = 7). plasma ANF was 81± 8 pg ml^-1 during VE, significantly higher than in the control animals. Although the sodium excretion increased more than ninefold in this group during VE, this increase was only 55 % of that in the VE group not given haloperidol. The DA and DOPAC excretion was increased by haloperidol, indicating a feedback effect of receptor blockade. DOPAC excretion was not increased further by VE, hut the excretion of DA increased by 15% and GFR increased by 19%. In conclusion, haloperidol reduced the natriuretic response to VE without impairing either the VE-induced release of ANF or the increase in GFR. The results indicate an important involvement of ANF and DA in the natriuretic response to VE.     

Influence of ruminal water-loading on renal sodium excretion and water intake following feeding in sheep.

We investigated the effect of ruminal water loading before feeding on the natriuretic and drinking responses that follow feeding. Six sheep fed 800 g of chaff drank 1360 +/- 150 mL during the 5 h immediately following feeding and increased renal Na excretion. Plasma Na concentration increased by 4 mmol L (-1) and plasma osmolality by 9 mosmol kg (-1) within 1.5 h and remained elevated. A rumen load of water administered before feeding prevented the increases in plasma Na and osmolality without affecting feeding. The natriuresis, water drinking and vasopressin secretion in response to feeding were abolished. Total sodium excreted during the experiment was halved in water-loaded animals compared with untreated animals (30.4 +/- 2.1 mmol (-1) cf. 63.8 +/- 2.9 mmol-1; P < 0.01). Ruminal loading with isotonic saline caused a 33% reduction in postprandial drinking, however, reducing cerebrospinal fluid NaCl concentration abolished postprandial drinking and natriuresis. Intravenous infusion of isotonic dextran appeared to delay the onset of water intake without changing the total volume of water drunk, suggesting a role of plasma volume in initiating drinking. We conclude from the data that central osmoregulatory mechanisms that include increased sodium excretion as well as thirst and vasopressin release are activated following food intake by sheep.