Kidney function in ANF-transgenic mice: effect of blood volume expansion

1991 ◽  
Vol 260 (1) ◽  
pp. R1-R5 ◽  
Author(s):  
L. J. Field ◽  
A. T. Veress ◽  
M. E. Steinhelper ◽  
K. Cochrane ◽  
H. Sonnenberg

Transgenic mice, created from inbred C3HeB/FeJ embryos, were used to overexpress selectively in the liver a fusion gene comprising mouse transthyretin (TTR) regulatory and atrial natriuretic factor (ANF) structural sequences. Animals were anesthetized, and kidney function was studied before and after blood volume expansion. Baseline urine volumes and electrolyte excretions were not significantly different from those of non-transgenic littermates, despite a markedly lower arterial blood pressure in the experimental group. A slightly lower glomerular filtration rate (GFR) in transgenics was not different statistically. Plasma ANF levels measured by radioimmunoassay were approximately 10-fold higher in the transgenic animals, compared with their nontransgenic siblings. After acute blood volume expansion, the diuretic, natriuretic, kaliuretic, and chloruretic responses were markedly enhanced in the transgenic group. Arterial pressure was increased as a result of hypervolemia, although it remained relatively depressed relative to the controls. GFR again was not different. We conclude that transgenic mice overexpressing ANF can maintain normal excretion of salt and water, possibly via ANF-induced reduction of renal perfusion pressure. After acute blood volume expansion, an increase in pressure may allow full renal expression of the chronically elevated ANF levels.

1984 ◽  
Vol 62 (7) ◽  
pp. 798-801 ◽  
Author(s):  
U. Ackermann ◽  
J. R. Rudolph

The blood volume of anesthetized rats was expanded acutely by 33% with donor blood while a caval snare was gradually tightened so that right atrial pressure (RAP) was prevented from rising (n = 6). In control experiments (n = 5) an aortic snare was used to hold mean arterial blood pressure near the values found in the experimental series. However, RAP was allowed to change freely and increased by 1.6 ± 0.4 mmHg (1 mmHg = 133.322 Pa) during volume expansion. When the two groups were compared, there were no significant differences between their mean arterial blood pressures (near 110 mmHg) or in their cardiac outputs (near 0.25 mL∙min−1∙g body weight−1). There were, however, significant differences between their renal responses to the volume load. When RAP was free to change, the rate of volume excretion [Formula: see text] increased to 30 ± 15 (SEM) μL∙min−1∙g kidney weight−1 (KW) from its control value of 3.49 ± 0.31 and the rate of sodium excretion [Formula: see text] increased to 3.59 ± 0.20 μequiv.∙min−1∙g KW−1 from its preinfusion value of 0.42 ± 0.10. When RAP was not allowed to increase during volume loading, [Formula: see text] and [Formula: see text] did not change from their respective preinfusion values (2.99 ± 0.46 μL∙min−1∙g KW−1 and 0.35 ± 0.10 μequiv.∙min−1∙g KW−1). The results imply that during acute blood volume expansion increased central vascular pressure is a prerequisite for the homeostasis of body water and salt.


1978 ◽  
Vol 234 (5) ◽  
pp. F386-F392
Author(s):  
U. Ackermann

The disappearance rate constant of radioiodinated human serum albumin (RIHSA) and 51Cr-tagged erythrocytes was measured in rats before and after intravenous, isoncotic blood volume expansion (6% bovine albumin; 75 or 33% of blood volume). Before volume expansion the average slope of the semilogarithmically plotted plasma RIHSA activity was -2.068 X 10(-3) +/- 0.146 X 10(-3) (SE) min-1. The slope was not significantly changed when tested by subsequent tracer injections which were made immediately after and 1 h after volume expansion. Preinfusion plasma volume (PV) was constant, but total erythrocyte volume (RCV) increased at a significant rate from 0.0253 +/- 0.0030 to 0.0300 +/- 0.0038 ml/g body wt over the 2-h period. PV was elevated and RCV was unchanged by the infusion, but both decreased significantly thereafter. The observed erythrocyte loss could not be accounted for by sampling or bleeding. Arterial hematocrit remained constant while RCV and PV were decreasing, and it was identical to whole-body hematocrit throughout. It was concluded that 1) isoncotic albumin expansion did not change the rate constant of transcapillary albumin loss; 2) nonsteady state PV could be calculated from a single preinfusion RIHSA dose; and 3) sequestration of blood may be a part of the rat's response to volume expansion.


1997 ◽  
Vol 272 (1) ◽  
pp. R148-R157 ◽  
Author(s):  
N. S. Stachenfeld ◽  
L. DiPietro ◽  
E. R. Nadel ◽  
G. W. Mack

To test the hypothesis that the inhibitory action of central blood volume expansion on thirst and renal fluid regulation is attenuated with aging, we monitored the drinking and renal responses of dehydrated older (70 +/- 2 yr, n = 6) and younger (24 +/- 1 yr, n = 6) subjects during 195 min of head-out water immersion (HOI), which shifts blood centrally and increases plasma volume (PV). Subjects dehydrated by exercising for 2 h at 36 degrees C in the evening and refraining from fluids overnight before HOI in 34 degrees C water or a seated control in water perfusion suit [time control (TC)] the next morning. Ad libitum water intake was allowed after 15 min of HOI. Dehydration decreased PV by 10.6 +/- 1 and 7.3 +/- 1.8% (P < 0.05) and increased plasma osmolality by 6 +/- 2 and 7 +/- 1 mosmol/kg H2O (P < 0.05) in older and younger subjects, respectively. Thirst ratings increased in both groups, but pre-HOI thirst perception on a line rating scale was lower in older (69 +/- 8 mm) than younger (94 +/- 6 mm, P < 0.05) subjects. Fifteen minutes of HOI restored PV by 7.8 +/- 1.0 and 5.7 +/- 1.0% in older and younger subjects, respectively, but suppressed thirst rating in younger subjects only (P < 0.05). Fluid intake was reduced in HOI compared with TC in younger (6.3 +/- 0.5 vs. 14.3 +/- 2.2 ml/kg, P < 0.05) but not in older (6.7 +/- 2.1 vs. 8.4 +/- 3.3 ml/kg) subjects. During HOI, older subjects had smaller suppression of plasma renin activity and aldosterone concentration but a greater increase in the plasma atrial natriuretic peptide concentration (P[ANP], P < 0.05). HOI increased fractional sodium excretion in both groups, but mean arterial pressure increased only in the older subjects (P < 0.05). We conclude that the inhibitory influence of central volume expansion on thirst and drinking behavior is diminished with aging. Furthermore, in contrast to younger people, HOI natriuresis is associated with exaggerated increases in P[ANP] and arterial blood pressure in older people, suggesting arterial baroreceptors may be involved in the fluid regulatory response to central blood volume expansion in older people.


1984 ◽  
Vol 247 (5) ◽  
pp. R833-R836 ◽  
Author(s):  
E. Tomomatsu ◽  
J. P. Gilmore

Studies were undertaken in the cat to determine if moderate hemorrhage or volume expansion significantly altered carotid sinus and aortic baroreceptor activity. In addition, the experimental design provided the opportunity to compare gain of the two sets of receptors. A 20% blood volume expansion increased mean arterial blood pressure 5.2% and carotid sinus nerve activity 14.7%, whereas a 20% hemorrhage decreased mean arterial blood pressure 10.8% and carotid sinus nerve activity 32.3%. For the aortic baroreceptors, a 20% blood volume expansion increased mean arterial blood pressure 5.9% and nerve activity 10.5%, and a 20% hemorrhage decreased mean arterial blood pressure 8.9% and nerve activity 21.0%. The blood pressure-discharge curves for the carotid sinus and aortic baroreceptors were not different. The well-known high sensitivity of atrial receptors was also documented. We conclude that both high- and low-pressure receptors apprise the central nervous system of the status of intravascular volume and pressure.


1970 ◽  
Vol 38 (6) ◽  
pp. 617-627 ◽  
Author(s):  
E. M. Clarkson ◽  
L. B. Talner ◽  
H. E. de Wardener

1. Sodium, potassium and para-amino hippurate (PAH) transport was studied in renal tubule fragments incubated in vitro in plasma taken from dogs before and after their blood volume was expanded with blood with which the dog was in equilibrium. The individuals who carried out the cell transport studies did not know the identity of the plasma samples. 2. Tubule fragments were less able to maintain a gradient of sodium and potassium, or to accumulate PAH when incubated in plasma obtained after blood volume expansion than when they were incubated in control plasma. 3. It is concluded that expansion of the blood volume causes the dog to change the concentration of some unknown circulating substance which influences sodium, potassium and PAH transport in separated tubule fragments. 4. It is proposed that this substance is partly responsible for the rise in urinary excretion of sodium that accompanies blood volume expansion in the intact animal.


1988 ◽  
Vol 8 (4) ◽  
pp. 1821-1825
Author(s):  
K A Kelley ◽  
J W Chamberlain ◽  
J A Nolan ◽  
A L Horwich ◽  
F Kalousek ◽  
...  

In an attempt to use mouse metallothionein-I (mMT-I) regulatory sequences to direct expression of human ornithine transcarbamylase in the liver of transgenic animals, fusion genes joining either 1.6 kilobases or 185 base pairs of the mMT-I regulatory region to the human ornithine transcarbamylase protein-coding sequence were used to produce transgenic mice. In mice carrying the fusion gene with 1.6 kilobases of the mMT-I 5'-flanking sequences, transgene expression was observed in a wide range of tissues, but, unexpectedly, expression in liver was never observed. Surprisingly, in mice carrying the fusion gene regulated by only 185 base pairs of the mMT-I 5'-flanking sequences, the transgene was expressed exclusively in male germ cells during the tetraploid, pachytene stage of meiosis.


1981 ◽  
Vol 241 (4) ◽  
pp. H571-H575 ◽  
Author(s):  
G. E. Billman ◽  
D. T. Dickey ◽  
K. K. Teoh ◽  
H. L. Stone

The purpose of this study was to investigate the effects of anesthesia, body position, and blood volume expansion on baroreflex control of heart rate. Five male rhesus monkeys (7.0-10.5 kg) were given bolus injection of 4.0 micrograms/kg phenylephrine during each of the following situations: awake sitting, anesthetized (AN) (10 mg/kg ketamine-HCl) sitting, AN recumbent, AN 90 degrees head down tilt, and AN 50% blood volume expansion with normal saline. beta-Receptor blockade was also performed on each treatment after anesthesia. Four additional animals were similarly treated after 20% blood volume expansion. R-R interval was plotted against systolic aortic pressure, and the slope was determined by linear regression. Baroreflex slope was significantly (P less than 0.05) reduced by 90 degrees head down tilt and 50% volume expansion both before and after beta-receptor blockade. A similar trend was seen after 20% volume expansion. These data are consistent with the thesis that baroreflex control of heart rate is reduced by central blood volume shifts.


1997 ◽  
Vol 30 (10) ◽  
pp. 1257-1256 ◽  
Author(s):  
J.R.V. Graça ◽  
F. de-A.A. Gondim ◽  
D.I.M. Cavalcante ◽  
J. Xavier-Neto ◽  
E.L.M. Messias ◽  
...  

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