AMERICAN JOURNAL OF PHYSIOLOGY Vol. 222, No. 1, January 1975. Printd

Right

atrium

in U.S.A.

and renal

sodium

excretion

SUSAN OPAVA STITZER AND RICHARD L, MALVIN De$mrtment of Physiology, University of Michigan, Ann Arbor, Michigan

STITZER, SUSAN OPAVA, AND RICHARD L. MALVIN. Right atrium and renal sodium excretion. Am. J. Physiol. 228(l) : 184-190. 1975.~Inflation of a balloon in the right atrium of 13 dogs resulted in salt and water retention not attributable to changes in GFR, RPF, filtration fraction, mean arterial pressure, left atria1 pressure, or renal venous pressure. The response to right atria1 balloon inflation was compared with the renal effects of constriction of the abdominal aorta above the renal arteries and constriction of the ascending aorta. Neither procedure evoked the same response as balloon inflation. Results suggest that the decrease in mean arterial pressure which accompanies balloon inflation accounts for only part of the decreased salt and water excretion. There was no significant difference between the responses of denervated and intact kidneys to right atria1 balloon inflation. A binary response to stretching of the right atrium is suggested, both components apparently involving hormonal mediation. right kidney

atria1

pressure;

renal

perfusion

pressure;

baroreceptors;

TN THE DOG the right atrium has for some time been regarded as the site of receptors that are involved in the reflex regulation of salt and water balance. In 1959, Anderson, McCaIly, and Farrell (2) demonstrated that stretching the right atrium with sutures caused the concentration of aldosterone in plasma to decrease. Coupled with the observation of Davis et al. (13) that increases in plasma aldosterone concentration followed constriction of the inferior thoracic vena cava, this suggested that right atria1 receptors existed which were sensitive to changes in right atria1 volume or pressure. Atria1 receptors which might respond to such stimuli had been described by Nonidez (23), and Coleridge et al. (12) had succeeded in isolating nerve fibers from the right atrium whose rate of firing could be diminished or abolished by constriction of the superior or inferior vena cava. Moreover, Gupta et al. (17) showed that graded decreases in blood volume correlated well with decreases in the rate of firing of right atria1 nerve fibers. In 197 1 Brennan et al. (10) demonstrated that increases in right atria1 pressure, brought about by inflation of a balloon in the right atrium, were associated with significant decreases in plasma renin activity, thus offering a possible mechanism for the previously observed changes in aldosterone secretion. The present study was undertaken in order to extend our knowledge in this area to the effect of alterations in right atrial pressure or volume on renal salt and water excretion.

48104

METHODS

All experiments were performed on sodium pentobarbital(30 mg/kg) anesthetized, mongrel dogs ranging in weight from 11 to 32 kg. The animals were deprived of food, but not water, overnight. A few of the animals received morphine sulfate (3 mg/kg) as a preanesthetic with the subsequent dose of pentobarbital reduced appropriately. All but three of the dogs were female. Following the induction of anesthesia, the animals were prepared as follows. Catheters were placed in the abdominal aorta via the right and left femoral arteries for the recording of mean arterial pressure (MAP) and the sampling of arterial blood. A catheter was introduced into the inferior vena cava, via the left femoral vein, for intravenous infusion. Both ureters were catheterized for urine collection following their exposure through one flank incision. In several animals renal venous pressure (RVP) was estimated by recording pressure in the inferior vena cava at about the level of the renal veins. Left atria1 pressure (LAP) was measured via a cardiac catheter placed directly into the left atrium through the left atria1 appendage. These and all other pressures, arterial and venous, were measured with Statham highand low-pressure transducers and recorded on a multichannel Grass polygraph. Electronic attenuation of the pulsatile components of the pressure waves produced a tracing of the mean pressures. The zero reference level used was the atmospheric pressure at the height of the dog’s heart. In those dogs in which the right atrium was to be stretched, a Foley indwelling urinary catheter ( 18 French), whose tip had been shortened, was inserted into the right atrium through an incision in the right atria1 appendage. This is a double-lumened catheter, one lumen leading to a balloon of 30-ml capacity, the other opening into the atrium at the tip of the catheter. The balloon was inflated with saline to stretch the atrium; the other lumen was used to record right atria1 pressure (RAP). To minimize artifacts in pressure measurement due to occlusion of the opening at the tip of the catheter, a second opening was cut in the wall of the catheter above the balloon. Thus there was a hole for measuring pressure both above and below the balloon. In another group of dogs, Foley catheters were placed in both the right and left atria. The ascending aorta was constricted by tightening, in an adjustable clamp, a loop of umbilical tape which had been placed around the aorta. The dogs subjected to constriction of the ascending aorta, and all other open-chested dogs,

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.KIGHT

ATRIUM

AND

SODIUM

185

EXCRETION

were ventilated throughout the experiments with room air, using a Harvard positive-pressure respiration pump. The pneumothorax was not reduced, but the wound was covered with saline-moistened gauze to minimize evaporative loss. In another series the abdominal aorta was constricted with a clamp placed immediately above both renal arteries. This group differed from all others in that the chests of these animals were not opened and the catheter in the .abdominal aorta measured pressure below the clamp. Mean arterial pressure was measured via a catheter placed in one carotid artery. Renal denervation was accomplished by identifying and -cutting all the renal nerves which could be visualized by extensive dissection. In addition a Z-cm segment of the renal artery was stripped of all adventitia. In two animals, following surgical denervation, lidocaine hydrochloride was applied topically to the renal vessels. Following surgery an intravenous infusion of isotonic saline was begun at a rate of approximately 3 ml/min. This infusion was continued for 30-60 min until a moderate increase in urine flow was observed. The infusion was then stopped briefly and a priming dose of creatinine (1.1 g) or creatinine and PAH (0.1 g), dissolved in 50 ml of water, was given intravenously. This was immediately followed by a sustaining infusion of creatinine and PAH in isotonic This infusion was continued saline also at 3 ml/min. throughout the experimen t. Two consecutive 1O-min control clearances were begun when u rine flow ra .tes had stabilized or a minimum of 30 min after the start of the second infusion. Following the control clearances, the desired experimental manipulation was carried out, either inflation of the balloon or adjustment of an aortic clamp. Thirty minutes were allowed to elapse before two consecutive experimental clearances were done in the same manner as the controls. The experimental procedure was then reversed by deflation of the balloon or removal of the clamp. Again 30 min elapsed, followed by two recovery clearances. clearances were done during In several animals additional the 30-min waiting periods. In those animals with balloons in both atria, the experimental manipulations consisted of a sustained inflation of the right atria1 balloon, during which the left atria1 balloon was inflated and deflated, followed finally by deflation of the right atria1 balloon* Each maneuver was

followed by a 30-min waiting period and two consecutive clearances. Urine and plasma samples were analyzed for Naf and K+ with a National Instrument Laboratories flame photometer, for creatinine according to the method of Bonsnes and Taussky (8), and for PAH according to the method of Smith et al. (26). Results were analyzed statistically by paired sample analysis, Student f test, and least-squares analysis of variance. RESULTS

Efect of inJation of a balloon in the rz$t atrium. The results of all experiments have been reported as either percent change or absolute change from control. In order to indicate the absolute magnitude of these changes, the mean values for renal and hemodynamic variables measured prior to inflation of a balloon in the right atrium are presented in Table 1. Control data from all other groups are also presented. In 13 dogs the balloon was inflated until RAP increased a minimum of 5 cmHz0 or to a maximum volume of 15 ml if a 5-cmHg0 increase in RAP was not observed as the balloon was inflated. The elect of balloon inflation on urine flow rate and sodium excretion is shown in Fig. 1. Results are the means for the experimental periods expressed as percent decrease from control. In all of the animals, inflation of the balloon resulted in a large decrease in salt and water excretion (I) values < -01). The mean decrease in sodium excretion (U,,V) for the group was 62.9 ‘ii> & 5.1; the mean decrease in urine flow rate (UFR) was 42.1 C? & 7.2. Upon deflation of the balloon, incomplete recovery toward the preinflation level of sodium excretion was observed, the mean postinflation value representing a decrease from control of 32.8 % & 9.6 (1’ < .Ol). However, in the recovery period urine flow rate had returned to a value not significantly different from control. Inflation of a balloon in the right atrium aflected a number of renal and cardiovascular parameters. Table 2 summarizes the effects of balloon inflation on all variables measured during these experiments. As shown in Table 3, the only significant correlations which could be demonstrated were between changes in UN,V and corresponding changes in GFR or MAP and between changes in urine flow rate and MAP. The possible roles of mean arteria1

Renal Variable

l&V,

peqlmin

Urine flow, ml/min UKV, peq/min GFR, ml/min RPF, ml/min Filtration fraction MAP, mmHg RAP, cmH& LAP, cmH20

Balloon

165 1.32 40.1 74.7 253 0.34 111 3.0 5.9

+ It =t + zt * zt + l

Inflation

31 (13) 0.20 (13) 5.7 (8) 6.1 (13) 45 (5) 0.03 (5) 5 (13) 0.6 (9) 1.9 (5)

Double-Balloon

86.4 0.96 30.7 52,5

Inflation

+ sit: zt +

63.1 (4) 0.31 (4) 3.2 (4) 3.7 (4)

111 * 5 (4) 4.8 zk 0.8 (3) 7.2 rt 1.3 (4)

Values are means & SE. Numbers in parentheses significantly different from intact kidneys by paired balloon-inflation group (P < .05).

Intact

Denervation*

Constriction Abdominal

Denervated

75.3 0.80

=t 14.7 zk 0.16

86.3 0.87

+ +

13.4 0.19

41.2

+

40.8

zt

5.2

5.7

120 + 8 (6) 2,8 zt 1.4 (6)

are numbers of experiments. * None t analysis. n = 6 pairs for each variable.

93.5 0.88 45.2 73.1

It + zt *

134 h

of Aorta

31.4 (7) 0.09 (7) 8.6 (5) 7.0 (7)

6t

(7)

of the values for t Significantly

Constriction Ascending

of Aorta

180 zt 26 (7) 1.23 + 0.31 (7) 73.6 220 0.34 102 2.5

denervated different

+ * AZ + zt

13.9 (7) 45 (7) 0.02 (7) 6 (7) 0.4 (5)

kidneys was from mean for

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186

S.

20 ----

5 L : P : 8

-80

-

-100

-

%Au,,v I Control

FIG.

and

urine

TABLE

Inflate

1. Effect of right atria1 flow rate, Results are

2.

i!$G!

balIoon means

UFR, UKV, GFR, RPF, w FF, MAP, (13 RAP,

%A (13) %A (13 %A (8) %A (13 %A (5) %A (5) A (5) AmmHg AcmH20

- -- ----..

R.

L,.

%AUFR

0

MALVIN

K 100

0

-/ 4’ 4*

50

.~

-50

l 3

,. -~----

--_I----

4

Deflate - I_ --.-.

/ I’

-I 00

Inflate ---

UN&v,

excretion

Uf right &id b&on i?i$dion I

Variable

AND

Deflate

inflation on sodium & SE. n = 13.

on renal and hemodynamic oarinhlcs --_-_ --

K

100

I

I

STITZER

Efect of changing left atrial pressure during sustained right atrial balloon injlution. In order to test the possibility that the results were due to changes in left atria1 pressure, rather than right atria1 pressure, four dogs were subjected to inflation and deflation of a balloon in the left atrium during sustained inflation of a balloon in the right atrium. The results of this series are shown in Fig. 3. In spite of the fact that during left atrial balloon inflation LAP approached, reached, or even exceeded its value prior to right atria1 balloon inflation, there was no significant alteration in sodium excretion or urine flow rate. Nor were there any significant differences in mean arterial pressure, right atria1 pressure, or GFR, as compared to their values during right atria1 balloon inflation alone. Efect of constriction of abdominal aorta on sodium excretion and urine Jilow rate. Since in all these series renal arterial pressure was decreased somewhat, in seven additional dogs reductions in renal arterial pressure were induced by constriction of the abdominal aorta above the renal arteries. The mean decrease in arterial pressure below the clamp, was 24.4 & 3.8 mmHg. Mean arterial pressure measured above the clamp increased only slightly, if at all, resulting

pressure and GFR in this response were investigated in later experiments. Efgct of renal deneruation on respunse to right &al balloon inj!ation. Six additional dogs were subjected to denervation of one kidney, the intact kidney serving as a control in each experiment. The response of each denervated kidney to right atria1 balloon inflation was compared to the response of its intact partner. Paired sample analysis revealed no significant difference between intact and denervated kidneys in their response to balloon inflation. Nor was the group of denervated kidneys as a whole significantly different from the balloon-inflation group with respect to changes in sodium excretion, urine flow rate, or GFR. This identity of behavior held in the postinflation period as well. Figure 2 compares the responses of intact and denervated kidneys to inflation and deflation of the right atria1 balloon. Q) zcc : ic --E

0.

/

KD 50

0’

IO0

,* -50

‘a

-.-_.__-

-662.9+5.1, -42.1*7.2, -12.W6.4, -7.ls2.9, -20.31t4.0, +14.8+2.6, +0.05~0.01, -8.8+2.9,

P < .Ol P < l Ol NS* P < .05 P < .Ol P < .Ol P < .Ol P < .Ol

-32.8zt9.6, -10.3+10.1, -5.U11.5, -2.9+3.2, -11.9+4.7, +16.3+4.6, +0.06%0.03, +4.5&4.0,

P < NS NS

+4,5+1-6,

P

Right atrium and renal sodium excretion.

Inflation of a balloon in the right atrium of 13 dogs resulted in salt and water retention not attributable to changes in GFR, RPF, filtration fractio...
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