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Department of Human Physiology, University of California, Davis, California 95616
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
ACKNOWLEDGEMENTS
FOOTNOTES
REFERENCES
ABSTRACT 
Albert, T. S. E., V. L. Tucker, and E. M. Renkin. Acute
alveolar hypoxia increases blood-to-tissue albumin transport: role of
atrial natriuretic peptide. J. Appl.
Physiol. 82(1): 111-117, 1997.
Plasma
immunoreactive atrial natriuretic peptide (irANP) and blood-to-tissue
clearance of 131I-labeled rat
serum albumin (CRSA) were
examined in anesthetized rats during hypoxic ventilation
(n = 5-7/group). Hypoxia (10 min) increased irANP from 211 ± 29 (room air) to 229 ± 28 (15%
O2, not significant), 911 ± 205 (10% O2), and 4,374 ± 961 pg/ml (8% O2),
respectively. Graded increases in
CRSA were significant at 8%
O2 in fat (3.6-fold), ileum
(2.2-fold), abdominal muscles (2.0-fold), kidney (1.8-fold), and
jejunum (1.4-fold). CRSA was
decreased in back skin and testes; heart, brain, and lungs were
unaffected. The increases in CRSA
were related to irANP and not to arterial PO2. Circulating plasma volume was
negatively correlated with whole body
CRSA. Graded increases in
extravascular water content (EVW) were found in the kidney, left heart,
and cerebrum and were positively related to
CRSA in the kidney. EVW decreased in gastrointestinal tissues; the magnitude was inversely related to
CRSA. We conclude that ANP-induced
protein extravasation contributes to plasma volume contraction during
acute hypoxia.
plasma volume; capillary permeability; albumin clearance; edema
INTRODUCTION IN A COMPANION PAPER (1), we described the changes in
plasma immunoreactive atrial natriuretic peptide concentration (irANP) produced by exposure of anesthetized rats to graded alveolar hypoxia. We showed that within 10 min of ventilation with 10% or 8%
O2, there was a large increase in
plasma irANP that was sustained throughout a 50-min period of hypoxia.
There was also an early decrement in plasma volume (PV) and a
corresponding increase in hematocrit, with little change in plasma
protein concentration. Similar reductions in intravascular volume are
produced by intravenous administration of ANP, suggesting that this
peptide acts at the capillary membrane to increase permeability to
fluid and plasma proteins (2, 19). Subsequent studies utilizing direct
measurements of plasma protein transport in intact rats (18, 24) and in single capillaries of frog mesentery (6) have corroborated this view.
The purpose of the present study was to evaluate the role of ANP in
mediating increases in protein and fluid extravasation during acute
hypoxia. These are the same experiments as reported in the companion
paper (1); however, here we focus on events occurring at the tissue
level. Blood-to-tissue albumin transport was measured in multiple
tissues by using a sensitive double-isotope technique. PV and
extravascular water (EVW) contents of individual tissues were also
assessed. Our main finding was that ventilation hypoxia increased
albumin extravasation into abdominal muscles, visceral fat, kidney, and
gastrointestinal tissues in a dose-dependent manner. Of all the
parameters measured, irANP was the best predictor of albumin
extravasation in these tissues. The importance of hypoxia-induced protein extravasation to fluid shifts occurring at whole-animal and
tissue levels is discussed.
METHODS
10
min]. A second set of blood samples was collected after 10 min of
gas treatment (t = 10 min). Albumin
extravasation was measured during the last 35 min of the gas
ventilation by using a double-isotope subtraction technique (15). To
start the measurement,
131I-labeled rat serum albumin
(131I-RSA, 6 µCi) was injected
intravenously at t = 15 min. Blood samples (100 µl) were collected 20 and 30 min after the start of gas
treatment and 5 and 15 min after isotope infusion for measurement of
plasma 131I activity. These blood
samples were replaced with similar volumes of lactated Ringer solution.
At t = 45 min (30 min after
131I-RSA injection), the clearance
measurement was completed by injection of
125I-RSA (6 µCi), which served
as a "reference tracer" for measurement of tissue intravascular
blood volumes. Terminal blood samples were collected 5 min later at
t = 50 min after the start of gas ventilation (35 min after injection of
131I-RSA). The rats were then
killed with intravenous KCl, and selected tissues were collected for
determination of radioactivity and water content. As described in the
companion paper (1), the amounts of injected
131I-RSA and
125I-RSA were known, enabling the
20- and 50-min samples to be used to calculate circulating PV at these
times.
Blood samples were centrifuged, and aliquots of plasma were diluted to
1 ml and placed in count tubes for determination of 131I and
125I activities. Uniform tissue
samples were rapidly dissected postmortem, blotted, and placed in
covered vials for 131I and
125I assay. Entire tissues or
organs were collected in the following cases: left lateral
gastrocnemius, heart (left and right ventricles), kidney, brain
(cerebellum and right cerebral cortex), and testis. For back skin,
abdominal muscle, visceral fat, lung (right middle lobe and left lower
lobe), and intestine (jejunum, ileum, cecum, and colon), samples
uniform in size and anatomic location were collected. Weights of
samples varied from 0.2 to 1.3 g among the different tissues and organs
but were similar within each category. After the tissue samples were
weighed, 100 µl of ethanol were added to each, and the vials were
placed in count tubes for determination of
131I and
125I activities. Plasma samples,
tissue samples, and tracer standards were counted in
131I and
125I channels of a gamma
scintillation counter (Searle Analytical, Des Plaines, IL) for 20 min.
For most samples, well >10,000 counts/sample were collected. The
counts were corrected for background, crossover from
131I to
125I (including effect of sample
volume on crossover), and decay of
131I. Crossover of
131I to the
125I channel was measured in each
experiment and ranged from 10.9 to 11.3%. After tissues were counted,
they were placed in an oven (95°C) and dried to constant weight
(±1 mg). To estimate EVW, total water contents (wet wt dry
wt) were corrected by subtracting plasma and erythrocyte water from the
total wet weight (18).
Calculation of albumin clearance.
Final distribution volumes of
131I- and
125I-RSA in organ and tissue
samples were calculated by dividing tissue counts by counts per
milliliter of final plasma. The volume of
125I-RSA in the tissues (after
5-min exposure) represents mainly intravascular ("small vessel")
PV. After 35 min of circulation, the volume of
131I-RSA in the tissues represents
not only intravascular PV but also an apparent distribution volume of
131I-RSA extravasated during the
experimental period. Subtraction of the
125I-RSA PV from the
131I-RSA volume yields the
extravascular albumin accumulation, measured as a plasma clearance of
albumin (CRSA) over 30 min. For
most tissues, interstitial fluid volumes are much larger than the
extravascular distributions of tracer in 30 min (21); therefore,
CRSA is taken as an estimate of
unidirectional albumin transport (albumin flux per unit plasma
concentration). A correction was made for a small drop in plasma
131I activity that occurred during
the experimental period by dividing clearance values by the ratio of
average to final 131I counts.
Average 131I activity was obtained
by approximate integration (trapezoidal rule) of the 5-, 15-, and
35-min counts (t = 20, 30, and 50 min of treatment, respectively). CRSA
values were normalized to tissue blood-free dry weight and expressed as
microliters per minute per gram
(µl · min
1 · g1).
Materials.
RSA, (Cohn Fraction V, Sigma Chemical, St. Louis, MO) was iodinated
with
131I
and
125I
(New England Nuclear-DuPont, Wilmington, DE) by using chloramine-T and
purified by anion exchange and repeated concentration-dilution with
Minicon filters (Amicon, Danvers, MA). Labeled RSA (specific activity = 10-50 µCi/mg) was repurified on the day of use to reduce free
I levels to <1%.
Statistics.
Data are expressed as means ± SE unless otherwise indicated.
Differences among treatment means were tested by using one-way analysis
of variance followed by orthogonal contrasts and Duncan's new
multiple-range test for post hoc comparisons among individual means.
Relationships among variables were evaluated by using linear (simple
and multiple) regression analyses. Differences are reported as
statistically significant when P 
0.05.
RESULTS
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1 · g1
for fat to 4.05 ± 0.79 µl · min1 · g1
for lung. The mean effects of graded hypoxic ventilation on
CRSA in individual tissues are
shown in Fig. 1. One rat from the 15% O2 group has been omitted from
Fig. 1 because its response behavior clearly deviated (>3 SD) from
the remainder of the group. This rat exhibited a large increase in
plasma irANP at 50 min (2,976 pg/ml), and
CRSA was elevated two times or
more basal values in several tissues. The remaining five rats
ventilated with 15% O2 exhibited
small but significant increases in irANP (+43%) by 50 min with no
detectable change in CRSA in any
tissue. Four out of five rats ventilated with 10%
O2 showed variable increases in
CRSA in one or more tissues;
however, group averages were not significantly greater than in
controls. In contrast, all six rats ventilated with 8%
O2 exhibited elevated
CRSA in multiple tissues, with the
average CRSA being significantly
higher than room air controls in visceral fat (3.6-fold), ileum
(2.2-fold), abdominal muscle (2.0-fold), kidney (1.8-fold), and jejunum
(1.4-fold). Higher CRSA values
were also noted in the lateral gastrocnemius, cecum, and colon; these
differences did not reach statistical significance. In back skin and
testis, CRSA was significantly reduced in both 10 and 8% O2
groups. Brain, heart, and lung clearances did not differ from control
values.
0.05.
Relationship between plasma irANP and CRSA. Figure 2 illustrates changes in CRSA plotted as a function of either PaO2 (A) or the logarithm of average plasma irANP concentrations (B). All data points from control and hypoxic groups are included in these graphs, including the aberrant 15% O2 rat in which irANP was elevated. PaO2 levels were similar between 8 and 10% O2 groups, yet irANP and CRSA reached their highest levels in the 8% O2 animals. The P values obtained from single regression analyses suggest that irANP was a better predictor of the CRSA response to hypoxia. Furthermore, when both factors were analyzed simultaneously by multiple regression, irANP alone (at constant PaO2) was a significant factor in the CRSA response to hypoxia, whereas PaO2 was not. In comparison, the decreases in CRSA observed in back skin and testis were not as strongly related to either irANP (P = 0.06 for both tissues) or PaO2 (P > 0.5) when both factors were included in the regression analysis.
), 15% (
), 10%
(
), 8% (
). A:
CRSA vs. PaO2.
PaO2 was measured at beginning of
clearance period (10 min after start of gas treatment).
B:
CRSA vs. log irANP. irANP values were obtained by pooling measurements collected at beginning and end of
clearance period. Solid lines, regression slopes (with model
P values). Dashed lines, regression
slopes for same tissues (Lat Gas substituted for Ab muscle) in
anesthetized rats infused with exogenous ANP representing
concentration-response relations under baseline conditions in normoxic
rats. [From Tucker et al. (18).]
The tissue specificity of the CRSA response to hypoxia in this study was strikingly similar to previous observations in rats given exogenous ANP (18, 22, 24). In our own experiments (18), infusion of synthetic ANP (400 ng · kg ·
1 · min1)
in rats given supplemental fluids to maintain PV increased clearance of
131I-BSA into gastrointestinal
tissues (2.9-4.6-fold), kidney (2-fold), fat (1.9-fold), skeletal
muscles (1.6-fold) and left ventricle (1.5-fold) but not in skin or
lungs (brain and testis were not sampled). However, the magnitude of
CRSA response for a given increment in irANP was greater in these previous experiments, particularly for gastrointestinal tissues. Regression slope
coefficients relating CRSA to log
irANP obtained in normovolemic rats given variable doses of ANP have
been included in Fig. 2B (dashed
lines) to illustrate this difference. [From Tucker et al.
(18).]
PV and EVW.
If elevated protein extravasation was a factor in the observed PV
reductions during hypoxia, we would expect to find
1) a negative correlation between
whole body CRSA and circulating PV and 2) a positive correlation
between CRSA and water content of individual tissues. The former relationship is illustrated in Fig.
3, in which changes in PV during the
clearance period are plotted as a function of whole body
CRSA, which was obtained by subtracting the 131I-RSA (35-min)
distribution volume from the
125I-RSA (5-min) distribution
volume. These data indicate that even though most of the
hypoxia-induced PV reduction occurred before the clearance measurement
(see Table 1), there was a definite linear relationship between
decreases in PV and increments in CRSA during the clearance
measurement period (P = 0.0001, r2 = 0.7132).
PV) as a function of whole body albumin
clearance (CRSA). PV were
calculated as difference between whole animal (5-min) tracer
distribution volumes obtained at beginning and end of clearance period.
CRSA measured over same 30-min
period were obtained by subtracting final
125I-RSA 5-min distribution volume from final
131I-RSA 35-min distribution
volume. Solid line, least squares regression coefficient
(P = 0.0001, r2 = 0.7132).
Small-vessel PV, measured at the termination of the experiment as the tissue 125I-RSA (5-min) distribution volume, and tissue EVW content evaluated by desiccation of the tissue samples are recorded in Table 2 for each treatment group. In testis, PV in rats ventilated with 10 or 8% O2 were significantly lower than in controls. For back skin and left ventricle, average PV were not different between groups by mean comparisons; however, linear-regression analyses indicated significant positive correlations between PV and the fraction of inspired O2, suggesting that hypoxia decreased PV in these tissues as well. Differences in EVW between control and hypoxia groups were insignificant for most tissues, including several of the tissues where CRSA was elevated. The jejunum, cecum, and colon all exhibited a trend toward lower EVW with increasing severity of hypoxia, and mean EVW in 8% O2 rats was significantly decreased in both jejunum (
10%) and colon (13%)
compared with that in controls. Of all the tissues with elevated
CRSA during hypoxia, increased EVW
was manifest only in the kidney. Water content was also increased in
the left ventricle and right cerebrum; however, these changes appeared
to be unrelated to changes in CRSA.
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DISCUSSION
In the companion paper (1), it was shown that plasma ANP levels were more closely related to the fraction of inspired O2 ("alveolar hypoxia") than to PO2 in arterial blood ("arterial hypoxemia"). This distinction allows us to evaluate the contribution of these factors to the observed changes in blood-to-tissue albumin transport. In tissues where increased CRSA was observed, these changes were better explained by elevations in plasma irANP as opposed to decrements in PaO2. The increases in CRSA were greater in 8% O2-treated animals, which had higher irANP levels, even though average PaO2 values were not different from animals ventilated with 10% O2.
Although changes in irANP and CRSA during hypoxia were clearly related, some of the tissues (most notably the jejunum and ileum) responded in a weaker manner compared with our own studies in nonhypoxemic rats infused with exogenous ANP (see Fig. 2). It seems reasonable to attribute this decreased sensitivity to known compensatory hormonal and hemodynamic changes produced by hypoxia. Increases in plasma vasopressin (12), sympathoadrenal activity (9), and chemoreceptor stimulation (13) during hypoxic ventilation could decrease microvascular pressures and/or surface area for exchange via selective vasoconstriction of peripheral tissues. Other investigators (23) reported selective gastrointestinal vasoconstriction in dogs given intravenous ANP in the presence of autonomic blockade. Thus it is possible that decreases in jejunum, cecum, and colon EVW observed in the present study resulted from ANP-mediated vasoconstriction. Hypoxia-induced reductions in tissue perfusion were also suggested by our observation of significantly lower CRSA and tissue PV values in tissues previously found to be "ANP insensitive" (e.g., back skin). Furthermore, the presence of factors that blunt the action of released ANP on albumin and fluid extravasation in the hypoxic state could explain the leveling off of PV reduction and hematocrit increase after their initial changes in the rats exposed to 8 and 10% O2. In hypoxic states where tissue perfusion and hydrostatic are better maintained (i.e., in conscious models), elevated CRSA would likely have a proportionally greater effect on PV redistribution into extravascular spaces.
Transfer of protein from the circulation to the interstitial compartment acts to augment transfer of fluid volume, potentiating the loss of PV and accumulation of interstitial fluid (16). Of what advantage to a hypoxic animal is increased extravasation of fluid and protein? Loss of circulating PV could certainly be considered detrimental to systemic circulatory function at a time when increased blood supply is needed to compensate for decreased arterial O2 content. However, there is considerable evidence that hypoxia-induced ANP release benefits cardiopulmonary function by reducing hypoxia-induced pulmonary hypertension (3, 8, 10). The antihypertensive action of ANP on the pulmonary circulation could occur directly, by relaxing pulmonary arterioles (7), or indirectly, by reducing cardiac output in the face of increased pulmonary vascular resistance (11, 19). The relationship between irANP and CRSA observed in the present study suggests that an additional effect of ANP could be to reduce cardiac output and filling pressures by increasing microvascular fluid filtration in peripheral tissues. In contrast to the minimal diuresis observed in our hypotensive pentobarbital sodium-anesthetized rats, renal excretory function is usually enhanced during acute hypoxia in conscious humans and animals (5). Under these conditions, a transvascular shift of protein into peripheral tissues would have the important consequence of minimizing the rise in plasma colloid osmotic pressure during diuresis, thus favoring PV reduction over the loss of interstitial fluid.
In humans exposed to 3-5 h of a simulated altitude of 4,500 m
(PO2 
40 Torr), Parving (14)
observed a small increase in the transcapillary escape rate of
131I-albumin from 5.6 to 6.5%,
which did not reach statistical significance. This led to the
conclusion that increased albumin extravasation was unlikely to have
contributed to the 7% reduction in PV observed in these subjects.
Average increases in whole body
CRSA in hypoxia groups were also
small and insignificant in the present study. However, a negative
relationship between whole body
CRSA and circulating PV was
clearly evident and statistically significant (Fig. 3). This finding
suggests that on a whole body basis, the albumin extravasation rate is
an insensitive index to changes in the driving force for fluid
filtration. This can be at least partially explained by the nonlinear
osmotic properties of serum albumin, which dictate disproportionately
larger deviations in osmotic pressure per unit change in albumin
concentration. Another problem is that whole body extravasation is
dominated by visceral tissues that comprise only a small fraction of
the total extracellular fluid volume. Taking these factors into
account, we conclude that the modest increases in local extravasation
rates in the present study resulted in the observed redistribution of
extracellular fluid.
The lack of a detectable increase in EVW in tissues where
CRSA was elevated is not
surprising for the following reasons. First, given that the total EVW
is much larger than the plasma space, a PV loss of the magnitude
observed in these experiments (15%) would have a relatively small
impact on EVW, particularly if it were distributed over several
tissues. Second, it is unlikely that either capillary hydrostatic
pressures or exchange surface areas were static in these experiments.
Hypoxic ventilation resulted in prominent hypotension in all groups and
reduced cardiac output in rats ventilated with 8%
O2 (see Ref. 1). Thus it is
possible that decrements in capillary hydrostatic pressure and flow
opposed increases in filtration induced by albumin extravasation. This might also explain why EVW decreased during hypoxia in most of the
gastrointestinal samples. Interestingly, the change in EVW (EVW)
appeared to be inversely related to the magnitude of
CRSA elevation
(CRSA) in these
tissues, with ileum showing the smallest EVW
(CRSA = 2.2-fold) and colon
showing the largest EVW
(CRSA = 1.3-fold). These data
suggest that increases in CRSA
antagonized absorptive forces in these tissues.
In light of the known permeability actions of ANP (6, 18, 24), it has been suggested that ANP contributes to hypoxia-induced pulmonary edema (4). In the present study, lung CRSA was unaffected by hypoxia, although EVW tended to increase in rats ventilated with 15 and 10% O2 (P = 0.09). The variability of EVW data was higher in the lungs than in other tissues; therefore, the possibility of a Type II error (i.e., the probability of failing to detect a real difference) cannot be ruled out. Interestingly, rats given 8% O2 (i.e., those with the greatest irANP response) had mean EVW values that were more similar to control. In this case, it is possible that a reduction in cardiac output, as was observed in a group of identically treated rats (1), could have contributed to a lower EVW via a reduction in pulmonary microvascular pressure. When regression analysis was performed on all data except those from the 8% O2 group, we found no significant correlation between average ANP levels and lung EVW (r2 = 0.12). Taken together, these observations do not support increased permeability as a mechanism linking ANP to pulmonary edema. However, given the high variability in lung EVW and the possibility that cardiac output was altered in the most severely hypoxic animals, a definitive relationship between ANP and lung fluid balance, whether it be positive or negative, cannot be ascertained from this study.
Increased pulmonary capillary transit time subsequent to reduction of cardiac output might favor uptake of O2 from alveolar gas (20). This is not likely to be of consequence under conditions where reductions of alveolar PO2 occur in the presence of normal alveolar membranes but could be beneficial when arterial hypoxemia is the result of pulmonary edema or fibrosis of the alveolar-blood interface. In this regard, ANP-induced PV reduction could improve arterial blood oxygenation by reducing pulmonary blood flow and minimizing pulmonary edema. This interpretation is supported by our finding of similar (if not higher) PaO2 during constant ventilation with 8% O2 compared with 10% O2.
Summary. In anesthetized rats ventilated with 10 or 8% O2, plasma ANP concentrations were elevated, and there was loss of fluid and protein from the plasma. In animals exposed to 8% O2, transport of tracer albumin was elevated in several tissues previously shown to be most sensitive to the action of exogenous ANP (abdominal muscle, visceral fat, kidney, jejunum, ileum) but not in ANP-insensitive tissues (lungs, heart, skin). In individual tissues, the increases in albumin transport showed significant correlation with plasma concentrations of irANP but less so with levels of PaO2. A notable depression in irANP sensitivity compared with previously observed effects of exogenous ANP was attributed to systemic vasoconstriction in the hypoxic rats, with subsequent reduction of functional capillary surface area. Loss of protein into peripheral tissues was associated with reductions of circulating PV during acute hypoxia. In intestinal tissues, decreases in EVW during 8% O2 were inversely related to the magnitude of CRSA elevation. We conclude that ANP-induced protein extravasation antagonizes reabsorbtive forces, thus favoring PV contraction during acute hypoxia. ANP-induced volume contraction could act in compensatory fashion by either improving arterial oxygenation or antagonizing pulmonary hypertension during acute hypoxia. Whether such a mechanism contributes importantly to the physiology or pathophysiology of hypoxia in the conscious state remains to be determined.ACKNOWLEDGEMENTS
We thank E. Bravo, T. Myers, and G. Johnson for technical assistance.
FOOTNOTES
Address for reprint requests: V. L. Tucker, Dept. of Human Physiology, Univ. of California-Davis, Davis, CA 95616-8671.
Received 1 February 1996; accepted in final form 4 September 1996.
REFERENCES
| 1. | Albert, T. S. E., V. L. Tucker, and E. M. Renkin. Atrial natriuretic peptide levels and plasma volume contraction in acute alveolar hypoxia. J. Appl. Physiol. 102-110, 1997. |
| 2. | Almeida, F. A., M. Suzuki, and T. Maack. Atrial natriuretic factor increases hematocrit and decreases plasma volume in nephrectomized rats. Life Sci. 39: 1193-1199, 1986. [Medline] |
| 3. |
Baertschi, A. J.,
J. Jiao,
D. E. Carlson,
R. W. Campbell,
W. G. Teague,
D. Willson,
and
D. S. Gann.
Neural control of ANF release in hypoxia and pulmonary hypertension.
Am. J. Physiol.
259 (Heart Circ. Physiol. 28):
H735-H744,
1990.
|
| 4. |
Bärtsch, P.,
S. Shaw,
M. Franciolli,
M. P. Gnadinger,
and
P. Weidmann.
Atrial natriuretic peptide in acute mountain sickness.
J. Appl. Physiol.
65:
1929-37,
1988.
|
| 5. |
Honig, A.
Peripheral arterial chemoreceptors and reflex control of sodium and water homeostasis.
Am. J. Physiol.
257 (Regulatory Integrative Comp. Physiol. 26):
R1282-R1302,
1989.
|
| 6. | Huxley, V. H., and D. J. Meyer, Jr. Atrial natriuretic peptide (ANP)-induced increase in capillary albumin and water flux. Adv. Exp. Biol. Med. 252: 23-31, 1988. |
| 7. |
Ignarro, L. J.,
K. S. Wood,
R. G. Harbison,
and
P. J. Kadowitz.
Atriopeptin II relaxes and elevates cGMP in bovine pulmonary artery but not vein.
J. Appl. Physiol.
60:
1128-1133,
1986.
|
| 8. |
Jin, H.,
R. Yang,
Y. Chen,
R. M. Jackson,
H. Itoh,
M. Mukoyama,
K. Nakao,
H. Imura,
and
S. Oparil.
Atrial natriuretic peptide in acute hypoxia-induced pulmonary hypertension in rats.
J. Appl. Physiol.
71:
807-814,
1991.
|
| 9. | Johnson, T. S., J. B. Young, and L. Landsberg. Sympathoadrenal responses to acute and chronic hypoxia in the rat. J. Clin. Invest. 71: 1263-1272, 1983. |
| 10. |
Klinger, J. R.,
R. D. Petit,
L. A. Curtin,
R. R. Warburton,
D. S. Wrenn,
M. E. Steinhelper,
L. J. Field,
and
N. S. Hill.
Cardiopulmonary responses to chronic hypoxia in transgenic mice that overexpress ANP.
J. Appl. Physiol.
75:
198-205,
1993.
|
| 11. |
Lee, R. W.,
and
S. Goldman.
Mechanism for decrease in cardiac output with atrial natriuretic peptide in dogs.
Am. J. Physiol.
256 (Heart Circ. Physiol. 25):
H760-H765,
1989.
|
| 12. |
Louwerse, A. M.,
and
J. M. Marshall.
The role of vasopressin in the regional vascular responses evoked in the spontaneously breathing rat by systemic hypoxia.
J. Physiol. Lond.
470:
463-472,
1993.
|
| 13. | Öberg, B. Effects of cardiovascular reflexes on net capillary fluid transfer. Acta Physiol. Scand. 62, Suppl. 229: 1-98, 1964. |
| 14. | Parving, H. H. The effect of hypoxia and carbon monoxide exposure on plasma volume and capillary permeability to albumin. Scand. J. Clin. Lab. Invest. 30: 49-56, 1972. [Medline] |
| 15. |
Renkin, E. M.,
W. L. Joyner,
M. Gustafson-Sgro,
G. Plopper,
and
L. Sibley.
Albumin extravasation rates in tissues of anesthetized and unanesthetized rats.
J. Appl. Physiol.
66:
2056-2060,
1989.
|
| 16. |
Taylor, A. E.
Capillary fluid filtration.
Circ. Res.
49:
557-575,
1981.
|
| 17. |
Tucker, V. L.,
and
V. H. Huxley.
O2 modulation of single-vessel hydraulic conductance.
Am. J. Physiol.
254:
H317-H323,
1988.
|
| 18. |
Tucker, V. L.,
K. E. Simanonok,
and
E. M. Renkin.
Tissue-specific effects of physiological ANP infusion on blood-tissue albumin transport.
Am. J. Physiol.
263 (Regulatory Integrative Comp. Physiol. 32):
R945-R953,
1992.
|
| 19. |
Valentin, J.-P.,
J. Ribstein,
and
A. Mimran.
Effect of nicardipine and atriopeptin on transcapillary shift of fluid and proteins.
Am. J. Physiol.
257 (Regulatory Integrative Comp. Physiol. 26):
R174-R179,
1989.
|
| 20. | Westendorp, R. G. J., A. N. Roos, H. G. V. Hoeven, M. Y. Tijiong, R. Simons, M. Frölich, J. H. M. Souverijn, and A. E. Meinders. Atrial natriuretic peptide improves pulmonary gas exchange in subjects exposed to hypoxia. Am. Rev. Respir. Dis. 148: 304-309, 1993. [Medline] |
| 21. |
Wigg, H.,
M. DeCarlo,
L. Sibley,
and
E. M. Renkin.
Interstitial exclusion of albumin in rat tissues measured by a continuous infusion method.
Am. J. Physiol.
263 (Heart Circ. Physiol. 32):
H1222-H1233,
1992.
|
| 22. |
Williamson, J. R.,
S. W. Holmberg,
K. Chang,
J. Marvel,
S. P. Sutera,
and
P. Needleman.
Mechanisms underlying atriopeptin-induced increases in hematocrit and vascular permeation in rats.
Circ. Res.
64:
890-899,
1989.
|
| 23. |
Woods, R. L.,
and
J. S. Smolich.
Regional blood flow effects of ANP in conscious dogs: preferential gastrointestinal vasoconstriction.
Am. J. Physiol.
261 (Heart Circ. Physiol. 30):
H1961-H1969,
1991.
|
| 24. |
Zimmerman, R. S.,
N. C. Trippodo,
A. A. MacPhee,
A. J. Martinez,
and
R. W. Barbee.
High-dose atrial natriuretic factor enhances albumin escape from the systemic but not the pulmonary circulation.
Circ. Res.
67:
461-468,
1990.
|
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