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Department of Physiology, University of the Witwatersrand, Johannesburg 2050, South Africa
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ABSTRACT |
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 TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
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This
study was designed to further examine the role of plasma ANG II
in the excretion of sodium in the Pekin duck, a bird with salt glands.
Renal and extrarenal (salt gland) excretion of an intravenously
administered isotonic saline load was monitored over a 4-h period in a
group of eight birds under two conditions: the control condition, in
which isotonic saline infusion decreased endogenous plasma ANG II from
102.6 to 16.5 pg/ml, and the experimental condition, in which ANG II
suppression was prevented by intravenous infusion of a 3.5 ng · kg
1 · min1 dose of
synthetic ANG II. ANG II infusion significantly decreased the total
sodium excretion (by 15%), primarily via an inhibition of salt gland
output. The results suggest that ANG II suppression facilitates the
excretion of an administered sodium load in birds with salt glands.
angiotensin II; kidney
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INTRODUCTION |
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TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
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THE RENIN-ANGIOTENSIN-ALDOSTERONE system (RAAS) has been extensively studied in both mammals (3, 6, 30) and birds (7, 8, 11, 27), and in both groups the foremost product of the RAAS, ANG II, is thought to play a vital role in salt and fluid homeostasis.
In birds, there is considerable evidence to suggest that ANG II is a sodium- and fluid-conserving hormone. For example, ANG II has been shown to stimulate aldosterone production in the adrenal steroidogenic cells of the domestic turkey (22) and the Pekin duck (17). In addition, centrally applied ANG II stimulates the release of arginine vasotocin, the antidiuretic hormone of birds, as well as stimulating water intake (28). In addition, under conditions of dehydration (19) and hemorrhage (29), plasma ANG II concentrations rise, and during salt loading the levels decrease (15, 18), providing further evidence that the physiological function of ANG II is to prevent extracellular fluid volume shrinkage, via antinatriuresis and antidiuresis.
In addition to the kidneys, marine and shore birds possess salt-secreting glands that assist in the elimination of excess electrolytes, mainly sodium chloride (9). It has been shown that ANG II has a strong inhibitory action on the salt glands of both kelp gulls (12) and Pekin ducks (5, 11). As there are no ANG II receptors on the salt glands (27), it is thought that ANG II acts indirectly via the central nervous system to inhibit salt gland activity (4). This action of ANG II again conforms to the idea that the peptide has a sodium-conserving action in birds.
However, some avian studies have shown that circulating ANG II actually promotes renal sodium and fluid excretion (7, 8, 15, 23). Clearly, this finding does not support the idea that the primary role of ANG II is sodium conservation and suggests a highly complex mechanism of action of ANG II in its role in sodium and fluid excretion.
The purpose of this study is to further explore the role of plasma ANG II on sodium and fluid regulation by the avian kidneys and salt glands. To this end, we monitored renal and extrarenal salt and fluid output, first during infusion of an isotonic saline load (which caused a decrease in endogenous ANG II) and then during saline infusion with added ANG II, which prevented the reduction in systemic ANG II. With this protocol, it should be possible to determine whether the suppression of circulating ANG II by the administration of a salt load is necessary for the elimination of that load, which would indicate that the action of endogenous plasma ANG II is normally antinatriuretic.
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MATERIALS AND METHODS |
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TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
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Animals
The studies were carried out using a group of eight adult (6 female, 2 male) Pekin ducks (Anas platyrhynchos) weighing 2.6-4.2 kg. The birds were kept in flocks at 22 ± 2°C and were fed commercial dry chicken feed. Pekin ducks are able to eliminate salt loads via both salt glands and the kidneys (9, 26), therefore, the ducks were given free access to isotonic saline as their only drinking fluid to activate their salt glands. All experiments were performed on conscious birds accustomed to the experimental conditions.Preparation of Animals
The bird was placed in a restraining stand with a canvas sling supporting its trunk, preventing the bird from excessive movement and immobilizing the legs. A flexible aseptic cannula (18-gauge Braunula, Braun, Melsungen, Germany) was inserted into a leg vein for the administration of saline and exogenous ANG II with an infusion pump (Perfusor III, Braun). A second cannula for collecting blood samples was placed in the other leg and kept patent by an infusion of heparinized (5 U/ml) isotonic saline at a rate of 0.05 ml/min. Silastic tubing was fixed to the nasal nares for the aspiration of salt gland fluid, and a perforated perspex bulb was inserted into the cloaca for urine collection as previously described (14).Experimental Procedure
After an equilibration period of 30 min, a blood sample (4 ml) was collected for the measurement of ANG II and for the determination of osmolality and electrolyte concentration. Then one of the following procedures was carried out.Control. Administration of isotonic saline at a rate of 2 ml/min for a period of 4 h.
ANG II infusion.
Synthetic ANG II was added to the isotonic saline and administered at a
dose of 3.5 ng · kg1 · min1
over the 4-h period.
Analytic Methods
Plasma, urine, and salt gland secretion were analyzed for osmolality and electrolyte content using a vapor pressure osmometer (Wescor 5100C, Logan, UT) and an I-Lyte Na+-K-Cl System
(Instrumentation Laboratory, ME002121, Milan, Italy), respectively.
Measurement of plasma ANG II was made after acetone extraction using a
previously described radioimmunoassay (18).
Statistics
The results are presented as mean values with standard errors (±SE). Data groups were subjected to repeated-measures ANOVA and Student-Newman-Keuls multiple-range tests when appropriate.| |
RESULTS |
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TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
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Administration of isotonic saline at a rate of 2 ml/min resulted
in a significant decrease in the circulating ANG II concentration. To
prevent this decrease in the experimental animals, synthetic ANG II was
added to the isotonic saline and the concentration was maintained at
about that of the baseline value (Table
1). We attempted to maintain the ANG II
at preinfusion levels; however, the actual concentration was somewhat
higher, although the difference was not statistically significant.
During the course of the experiments, there were no significant changes
in the plasma osmolalities, which had preinfusion values of 293.5 ± 3.6 and 291.1 ± 3.1 mosmol/kgH2O in the control
and ANG II-infused birds, respectively.
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In both the control and ANG II-infused birds, urinary output and salt
gland secretion began ~30 min after the start of isotonic saline
infusion and remained reasonably stable for the duration of the
experiment. The maintenance of an elevated plasma ANG II concentration
did have an effect on fluid outputs; however, the responses
differed with respect to the kidneys and the salt glands. The salt
glands tended to secrete at a higher rate and osmolality in the control
birds, although the differences did not reach statistical significance
(Table 2), whereas the urine from the ANG
II-infused birds was excreted at a slightly higher rate but at
unchanged osmolality (Table 3). When
expressed in terms of the total outputs, the ANG II-infused birds
excreted significantly more fluid via the kidney but significantly less
fluid via the salt glands than the control animals. The combined effect
of an increased renal fluid excretion and reduced salt gland fluid
secretion meant that overall there was no significant difference in the
total fluid outputs between the control and ANG II-infused birds (Fig.
1).
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With regards to the sodium excretion, both control and experimental
birds showed a significant increase over time, elicited by both the
salt glands and the kidneys. However, once again there were
differential responses of the salt glands and kidneys to ANG II
infusion, which essentially mirrored the flow rate responses. For the
salt glands, the reduced osmolality and flow rate produced a
significant fall in the total sodium excreted via this route in the ANG
II-infused animals. The sodium excretion by the kidneys, however, was
higher in these birds, although not by an amount equivalent to that
retained by the salt glands so that overall the total sodium output via
kidneys and salt glands together was significantly lower when ANG II
was infused than when the peptide was suppressed (Fig.
2).
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DISCUSSION |
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TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
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The precise role of endogenous plasma ANG II in the handling of sodium and water in birds is currently not fully understood. Although there is a significant amount of evidence to suggest that systemic ANG II is a sodium-conserving hormone (18, 19, 27), it has also been demonstrated that ANG II infusion can promote renal sodium excretion in a variety of avian species (7, 8, 12, 23). Because of this lack of clarity, the objective of this study was to evaluate the role of plasma ANG II in the excretion of an intravenously administered sodium load in a bird using both kidneys and salt glands to eliminate the load.
With this model, we found that the maintenance of plasma ANG II concentrations at or slightly above preinfusion levels did indeed reduce the overall excretion of the sodium load but did not change the fluid output. Although this suggests that endogenous plasma ANG II has a sodium-conserving action in the ducks, the picture is complicated by the fact that the responses of the two excretory organs eliminating the salt and fluid were markedly different. In the case of the salt glands, the ANG II infusion reduced the sodium and water excretion via this route to only ~50% of that in the control situation. This inhibitory action of ANG II on avian salt glands conforms to previous findings (5, 12) and is clearly supportive of a salt- and fluid-conserving action for plasma ANG II in birds.
With respect to the kidneys, however, the situation appears to be much more complex and certainly does not demonstrate a sodium- and/or fluid-conserving action for ANG II. The urinary output of sodium and water was significantly elevated by ANG II infusion, a finding that has been noted in other earlier studies (7, 8, 12, 23), although it should be noted that in the previous investigations plasma ANG II levels were not just maintained but elevated, sometimes to supraphysiological levels.
It is this natriuretic/diuretic action of ANG II that confuses our understanding about the physiological role of this peptide in birds and points to a complexity in ANG II control of avian renal function. Previous studies have shown that the renal action of plasma ANG II is dose dependent and, in addition, can be modulated by osmotic status. In conditions of salt and fluid loading, all doses of exogenously applied ANG II promote sodium excretion (12, 15), whereas in the absence of salt and fluid loading the action of ANG II is biphasic, with low doses causing renal sodium retention but high circulating levels inducing natriuresis. The transition from antinatriuretic to natriuretic effects of ANG II clearly needs further investigation if the physiological role of this peptide is ever to be fully defined, and there is a number of potential starting points. For example, in mammals the increased renal excretion of sodium induced by high doses of ANG II is related to an increase in renal arterial pressure (24), and this may also be the case in birds. Alternatively, the observed increase in sodium excretion may not be a direct action of ANG II but rather via an interaction with other renotropic agents; again, there are several candidates. For instance, PGs may be involved, because in mammals it is well established that systemic ANG II can release PGs within the kidney (20, 31), and in both birds and mammals PGs produce natriuresis and diuresis (1, 2). Similarly, catecholamines could play a role as they are known to be released by ANG II in ducks (33) and have been shown to have marked natriuretic effects in the same species (22).
Another renotropic agent likely to be involved is atrial natriuretic peptide (ANP). The plasma concentration of this hormone is known to be increased by hypervolemia (14) and it has been shown to stimulate renal function in ducks (25) and chickens (13). It has also been shown in mammals (32) that ANG II stimulates ANP release, and so it would obviously be of interest to know whether the circulating concentrations of ANP in the present study were significantly higher in the ANG II-infused animals than in the controls, although it would be difficult to explain why only the kidney responded to the elevated ANP and not the salt glands, which are also known to be stimulated by systemic ANP (16). Unfortunately, we were not able to measure plasma ANP concentrations in the present study, and, clearly, further studies are required to examine the mechanism(s) behind the complex effect of ANG II on renal sodium and fluid excretion.
In this study, we interpreted the increased renal excretion in ANG II-infused birds as being a direct consequence of the ANG II elevation; this may not, in fact, be the case. Rather the change in renal function may be a result of the strong salt gland response to ANG II. Afferent control of salt gland and kidney function is known to be closely integrated (26), with the receptive elements controlling both systems, probably colocalized in the rostral brain stem, e.g., in the tissues surrounding the third cerebral ventricle (10, 26). Hence, a reflex stimulation of renal function associated with salt gland inhibition may be the dominant factor regulating renal function, and this could easily be independent of circulating ANG II.
Although the urinary sodium and water excretion in ANG II-infused birds was greater than in the control situation, the relative increase in sodium output was not as great as the decrease via salt gland inhibition. Hence, when sodium excretion via both routes is taken together, the overall effect of an elevated plasma ANG II is one of sodium conservation. This observation is in agreement with studies carried out in humans (30), which showed that ANG II suppression is essential for the excretion of a sodium load. Therefore, although there remain many unanswered questions about the precise renal actions of plasma ANG II, this study does indicate that in birds the suppression of ANG II concentration facilitates the overall excretion of an administered sodium load.
Perspectives
As in mammals, the avian RAAS is generally regarded as a sodium-conserving system, therefore the frequent observation that the elevation of plasma ANG II concentration in birds leads to an increased (renal) excretion of sodium becomes difficult to reconcile. In the present study, although the findings are consistent with an overall sodium-conserving role for plasma ANG II, only its sodium-retaining actions at the salt glands were demonstrable. The renal actions of ANG II appear to be extremely complex, and the factors that control the apparent transition from antinatriuretic to natriuretic effects of plasma ANG II need detailed characterization. Future studies will have to pay close attention to experimental design, particularly the osmotic status of the animal. For example, the use of salt and volume loading, which physiologically would be associated with a depression of plasma ANG II levels, appears to change the action of the peptide so that elevated concentrations produce confounding effects. Clearly, there is still a great deal lacking in our understanding of the physiological role of plasma ANG II and we believe that this holds true not only for birds but for mammals, too.| |
ACKNOWLEDGEMENTS |
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The animal care provided by the Central Animal Unit of the University of the Witwatersrand was much appreciated.
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FOOTNOTES |
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This study was approved by the Animal Ethics Committee of the University of the Witwatersrand (clearance Nos. 97/3/3 and 99/68/3) and was supported by funding from the National Research Foundation of South Africa and the Technikon Witwatersrand Research Council.
Address for reprint requests and other correspondence: M. K. Heinz, Dept. of Physiology, 7 York Rd., Parktown, Johannesburg 2193, South Africa (E-mail: myriamh{at}twrinet.twr.ac.za).
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Received 27 October 2000; accepted in final form 1 March 2001.
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REFERENCES |
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TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
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