EXPT.
NO.

Onn bwNnN

12
13

17
22
23

TABLE VI

EFFECT OF INCREASED URETERAL PRESSURE
ON RENAL BLOOD FLOW IN
INTACT DENERVATED KIDNEYS

t

WITHOUT DIURESIS E. P, WITH DIURESIS
(mm Hg)
A UP* A RBF A Up* A RBF
(mm Hg) (cc/min) (mm Hg) (ce/min)

0> 71> 73 1687 1807? 122
0°? 75 2767 213
0> 85 183> 150
0> 8 1207 94

0> 65 156> 130 44

0> 24 276> 255

0> 44 162> 156 45

0> 63 188> 162

O> 24> 33 264 246> 237 23

0> 53 140> 150 48

0> 17> 42 150> 158> 138 16

0> 25> 68 1107 1147 92 38

0> 93 137> 120 85

0° 35° 59-216 228° 198 = 338

0> 72 207> 228 0? 95 2587 180

0> 31 144> 14] 25

*Intermediate values of UP are to be associated with intermediate values of RBF.

7Determined by value of deep venous pressure and/or value of increased large vein pres-

sure resulting in significant decrease in renal blood flow.

TABLE VII

EFFECT OF CAROTID ARTERY OCCLUSION ON
VASCULAR RESISTANCE OF ISOLATED
PERFUSED KIDNEY*

CAROTID OCCLUSION
A SYSTEMIC ARTERIAL A RENAL RESISTANCE

8 EXPTS. PRESSURE (mm Hg) (mm Hg/cc/min)

MEAN 132? 193 18> 2.4

S. E. 3.9 12.5 0.2 0.4
RELEASE OF CAROTID OCCLUSION

6 EXPTS.

MEAN 171> 125 197° 1.6

S. E. 7.9 5.2 0.2 0.3

“Arterial pressure or renal blood flow of isolated kidney maintained constant.

7
E.P.
(mm Hg)

48

—12— 0.5, GOVERNMENT PRINTING OFFICE : 1964 0~732-430


The effect of large vein pressure elevation on
renal hemodynamics is summarized in 17 intact
kidney experiments (Table IV). Large vein
pressure was successfully increased by adjust-
ment of screw clamp on the venous outflow
catheter. On the average, renal blood flow is
little influenced by increases in renal vein pres-
sure (orifice vein pressure) through a wide
range of venous pressure values (045 mm.
Hg). Total resistance (RAP-LVP/F) progres-
sively decreases as a function of increased
yenous pressure varying from 0 to 60 mm. Hg.
Renal artery pressures are maintained relative-
ly constant in each experiment through the en-
tire range of venous pressure alteration. Deep
venous pressures were measured in four experi-
ments in which large vein pressures were in-
creased as in the previous table. Table V demon-
strates the effect of increased large vein pres-
sure on total resistance (RAP-LVP/F) and
venous segment resistance (DVP-LVP/F) in
the intact kidney. Renal artery pressure is main-
tained relatively constant in each experiment.
It is seen that renal blood flow remains rela-
tively constant until large vein pressure approxi-
mates or exceeds resting deep vein pressure
(extravascular pressure). Total resistance (Rx)
decreases as a function of elevated large vein
pressure (LVP), which is primarily due to the
drop in venous segment resistance (Rv).

The effect of ureteral pressure elevation on
renal blood flow in intact kidneys, with and
without a diuresis is illustrated in Table VI.
Control (pre-ureteral pressure elevation) extra-
vascular pressures are shown in most experi-
ments. Ureteral pressure was increased by oc-
clusion of the ureteral catheter following cath-
eter attachment to a pressure transducer. Re-
sulis show that a decrease in renal blood flow
ordinarily occurs when ureteral pressure ap-
proximates or exceeds resting extravascular
pressure.

Arterial pressures in the present experiment
were increased by transfusion of homologous
blood. Other investigators (26) have achieved
this by carotid artery occlusion. Several experi-
ments were carried out utilizing the latter pro-
cedure to determine if extrarenal influences
were present to interfere with renal autoregula-
tion. Table VII illustrates the results from these

studies. An isolated kidney from a donor dog
was perfused at constant arterial pressure or
flow with blood from an intact dog. The com-
mon carotid arteries of the dog were tempo-
rarily occluded and the vascular effects on the
isolated kidney were measured. Changes in re-
sistance in the perfused kidney could only be
due to changing concentrations of vasoactive
agents in the blood. Results from eight experi-
ments show that when bilateral carotid occlu-
sion occurs, constrictor agents are released into
the blood which cause a marked rise in renal
resistance. Conversely, when carotid occlusion
is released, a marked drop in toial resistance
in the isolated perfused kidney occurs. Because
of the magnitude of the resistance changes when
compared to the corresponding systemic artery
pressure alterations, autoregulation of a kidney
may be grossly interfered with by the extrinsic
humoral influences. These experiments were
also carried out in intact kidneys, and similar
complicating extrarenal influences were also
noted. It was shown that intra-arterial injections
of catechol amines in the intact kidney result
in marked decreases in deep venous pressure
(extravascular pressure). Therefore, the effect
of carotid occlusion on the intact kidney is two-
fold: (a) renal artery vasoconstriction and
(b) a tendency to reduce extravascular pressure.
These carotid occlusion experiments demon-
strate the important role of extra-renal humoral
influences on renal vascular resistance.

DISCUSSION

Results from the present work on the intact
denervated kidney are in agreement with pre-
viously reported isolated perfused kidney
studies (8-15) regarding the important role of
extravascular pressure in the autoregulatery
phenomenon. Findings from four independent
procedures in determining extravascular pres-
sures show cssential agreement. These proced-
ures are: values of (a) deep vein pressure (ar-
cuate vein or deeper); {b) needle pressure;
(c) large vein pressure increase which results
in a significant fall in renal blood flow and
(d) ureteral pressure increase producing a drop
in renal blood flow. These independent meas-
urements appear to adequately substantiate
needle pressure measurements previously re-

ported in this laboratory (8-15), and by others

—3—



RENAL VASCULAR RESISTANCE

Nn
ry

TISSUE PRESSURE

BOWMAN'S CAPSULE
EXTRAVASCULAR PRESSURE

POST-GLOMERULAR VISCOSITY
MYOGENIC RESPONSE

METABOLIC RESPONSE

i

100 200

RENAL ARTERY PRESSURE
(mm Hg)

Ficure 3. Mechanism of autoregulation: suggested components of resistance. (Qualitative re-
lationships. )

—s—


study, initially occurs when ureteral pressure
is well below the level of control extravascular
pressure. A myogenic reflex resulting from a
decrease in pre-glomerular transmural pres-
sure (due to increased extravascular pressure)
therefore appears improbable. Other possibili-

ties have been pointed out by Selkurt (24).

Figure 3 is a schema of the proposed mechan-
isms operating te produce renal autoregulation.
The several suggested components of resistance
are depicted in a qualitative fashion. General-
ized extravascular pressure (tissue pressure) is
seen io account for approximately 2/3 of the
total resistance change. Other components, each
accounting for fractions of the total resistance
are, Bowman’s capsule extravascular pressure
(10); changes in post-glomerular viscosity
(10, 12); the myogenic response (4, 15, 16,
26) and metabolic factors (15). It is probable
that the contributions of each of the proposed
components of resistance may vary in magni-
tude in kidneys as is suggested by the results
of the present and past (8-15) investigations.

REFERENCES
1. Bounous, G.. M. Onnis, and H. B. Shumacker, Jr. The

abolition of rena) autoregulation by renal decapsulation.
Surg. Gynec. & Obstet. 111: 682-690, 1960.

Brun, C,, C. Crone, H. G. Davidsen, J. Fabricius, A. T.
Hansen, N, A. Lassen, and O. Munck. Renal interstitial
pressure in normal and in anuric man: Based on wedged
renal vein pressure. Proc. Soc. Exp. Biol. Med. 91: 199.
202, 1956.

. Chatterjee, S. K., and A. K. Dutta. Anatomy of the intra-
renal distribution of renal arteries of the human kidney.
J. Ind. Med. Assoc. 40: 155-162, 1963.

XN

4, Folkow, B, Transmural pressure and vascular tone—some
aspects of an old controversy. Arch. int. Pharmacodyn.
139: 455-459, 1962.

Haddy, F. J. J. Scott, M. Fleishman. and D. Emanuel.
Effect of change in renal venous pressure upon renal vas-
cular resistance, urine and lymph flow rates. Am. J.
Physiol. 195: 97-110, 1958,

. Haddy, F. J., J. Scott, M. Fleishman, and D. Emanuel.
Effect of change in flow rate upon renal vascular re-
sistance. Ant. J. Physiol. 195: 111-119. 1958.

7, Haddy, F. J. and J. B. Scott. The relation between renal
lymph’ pressure and autoregulation of renal blood flow.
Physiologist 6: 194, 1963.

8. Hinshaw, L. B., S. B. Day, and C. H. Carlson. Tissue pres-
sure as a causal factor in the autoregulation of blood
flow in the isolated perfused kidney. Am. J. Physiol. 197:
309-312, 1959.

w

ry

9. Hinshaw, L. B., H. M. Ballin, $. B. Day. and C. H. Carl-
son. Tissue pressure and autoregulation in the dextran.
perfused kidney. Am. J. Physiol. 197: 853-855, 1959.

10. Hinshaw, L. B., and C. H. Carlson. Mechanisms of auto-

regulation in isolated perfused kidney. Proc. Soc. Exptl.
Biol. Med, 103: 373-375, 1960.

1. Hinshaw, L. B, R. D. Flaig, R. L. Logemann and C. H.
Carlson, Intrarenal venous and tissue pressure and auto-
regulation of blood flow in the perfused kidney, Am. J.
Physiol. 198: 891-894, 1960.

12, Hinshaw, L. B, R. D. Flaig, C. H. Carlson, and N. K.
Thuong. Pre- and postglomerular resistance changes in
the isolated perfused kidney. Am. J. Physiol. 199: 923-
926, 1960.

13. Hinshaw, L. B.. and D, M. Worthen. Role of intrarenal
venous pressure in the regulation of renal vascular re-
sistance. Circulation Res. 9: 1156-1163, 1961.

14. Hinshaw, L. B., C. M. Brake, P. F, Iampietro. and T. E.
Emerson, Jr. Effect of increased venous pressure on renal
hemodynamics. Am. J. Physiol. 204: 119-123, 1963.

15. Hinshaw, L. B., B. B. Page, C. M. Brake, and T. E.
Emerson, Jr. Mechanisms of intrarenal hemodynamic
changes following acute arterial occlusion. Am. J. Physiol.
fin press)

16. Johnson, P. C.. W. H. Waugh, and L. B. Hinshaw. Auto-
regulation of blood flow. Science 140: 203-205, 1963.

17. Kiil, F., and K. Aukland. Renal concentration mechanism
and’ hemodynamics at increased ureteral pressure during
osmotic and saline diuresis. Scand. J. Clin. Lab. Invest.
13: 276-287, 1961.

18. Montgomery, A. V., E. R. Mickle, H. G. Swann, and J. J.
Coleman. A measure of intrarenal pressure. Texas Reports
Biol. Med. 8: 262-270, 1950.

19. Morison, D. M. A study of the renal circulation with
special reference to its finer distribution. Am. J. Anat.
37: 53-93, 1926.

20. Rusznyak, Istvan, Mihaly Foldi, and S. Gyorgy. Lymphat-

ics and Lymph Circulation. New York; Pergamon Press,
1960; (pgs. 116, 688-703).

21. Samelius, U., and A. Astrom. On pressure flow relation-
ships in the cat kidney. Acta Physiol. Scand. 50 (Suppl.
175): 139, 1960,

22. Scher. A. M. Mechanism of autoregulation of renal blood
flow. Nature 184: 1322-1323, 1959.

23. Schmidt, C. F., and J. M. Hayman, Jr. A note upon
lymph formation in the dog’s kidney and the effect of
certain diuretics upon it. Am. J. Physiol. 91: 157-160,
1929.

24. Selkurt, E. E. Effect of ureteral blockade on renal blood
flow and urinary concentrating ability. Am. J. Physiol.
205: 286-292, 1963.

25. Swann. H. G., V. Moore, and A. V. Montgomery. Influ-
ence of arterial pressure on intrarenal pressure. Am. J.
Physiol. 168: 637-641, 1952.

26. Thurau, K.. and E. Wober. Zur Lokalisation der autoreg-
ulativen Widerstandsanderungen in der Niere. Pflueger
Arch. ges. Physiol. 274: 553-566, 1962.

Winton, F. R. Hydrostatic pressures affecting the flow
of urine and blood in the kidney. The Harvey Lectures,
Series XLV, New York, Acad. Press. 1951-52, pp. 21-52.

28. Winton, F. R. Intrarenal pressure and renal blood flow.
Transactions of the Third Conference, Renal Function:
New York. Josish Macy. Jr. Foundation, 1951, pp. 51-102.

27.


(25, 27, 28). It appears that if bleeding is pro-
duced b; the tissue pressure needle, it is venous
in origin. Since deep venous transmural pres-
sures approximate zero mm. Hg (11, 13, 14),
deep venous pressures are reflections of tissue
pressure. A penetrating needle may be apt to
puncture veins because of the large volume
occupied by the venous segment (3, 19). Extra-
vascular pressures obtained in the present study
are of similar magnitude, although slightly
higher, than those previously reported in isolat-
ed perfused kidneys (8-15).

Autoregulation was observed in the present
study when both renal arterial and renal venous
pressures were altered. “Renal arterial” auto-
regulation was found to be produced in’ large
part by changes in extravascular pressure,
whereas “renal venous” autoregulation was
brought about by failure to alter resting extra-
vascular pressures until approximated in magni-
tude by large vein pressure.

It has been shown (26) that capillary and
tubular pressures are uninfluenced by changes
in renal artery pressure. However, these report-
ed results (26) may be accounted for by release
of catechol amine-like agents following carotid
artery occlusion, as demonstrated in the present
study. Release of constrictor agents into the
blood as a result of carotid occlusion would pro-
duce an exaggerated degree of autoregulation
by afferent arterial constriction, and would pre-
vent a rise in extravascular pressure. Compres-
sion of the aorta above the renal artery would
act in reverse fashion to offset normal changes
in extravascular pressure.

Values of directly measured deep venous
pressures in the present study are corroborated
by the other previously described procedures
(8-16). Additional information validating this
measurement is as follows: (a) obstruction of
the venous bed by the catheter is unlikely be-
cause of the massive degree of collateralization
(2, 3, 19); (b) the size of the catheter does not
influence the magnitude of the pressure (16),
and (c) the greater the degree of autoregulation
when either arterial or venous pressures are
increased, the higher is the recorded deep venous
pressure value (12-15).

Obstruction of lymphatic vessels did not ac-
count for the high values of extravascular pres-

sure in the present study. No lymphatic vessels
were ligated and results in the intact study were
similar to isolated perfused preparations (8-.
15). Lymphatic outflow, reportedly lesser in
magnitude when arterial pressure is increased
than during venous pressure elevation (5, 6) is
entirely consistent with the present and past
(8-15) investigations: increasing arterial pres-
sure results in increased extravascular pressure
which would compress lymphatic vessels. Lym-
phatic flow therefore autoregulates (6, 7). The
mag) .iudes of tissue pressure and lymph flow
rale are inversely related (20). On the other
hand, increases in large vein pressure would
increase peritubular transmural pressure but
extravascular pressure tends to remain constant
through wide ranges of venous pressure altera-
tion (14). Lymphatic outflow would therefore
increase. Caution should be exercised in the in-
terpretation of the relationship of lymphatic
pressures and flows and autoregulation, for ex-
ample, lymphatic pressure should not be taken
as a measure of tissue pressure (7) unless the
tip of the measuring catheter is in the renal
parenchyma (13). This relationship also exists
between large vein and deep (arcuate, inter-
lobular) venous pressures (13, 16). It is diffi-
cult to interpret the significance of changes in
lymphatic pressures and flows for the following
additional reasons: lymph vessels of capsule
and parenchyma anastomose (20); acute lym-
phatic congestion has no effect on GFR and
RBF (20); injections of epinephrine result in
a decrease in urine flow but an increase in
lymph flow (23). The latter observation could
be explained by decreases in glomerular and
tissue pressures.

There has been much recent interest in the
effect of increased ureter: | pressure on renal
hemodynamics (13, 17, 24, 27). Results from
the present study are in agreement with those
reported by Kiil and Aukland (17), Winton
(27), and Waugh (W. H. Waugh, personal
communication). Renal blood flow falls when
ureteral pressure rises to values approximating
or exceeding resting (control) extravascular
pressure. In several experiments, renal blood
flow significantly increased following ureteral
occlusion. This has also been reported by others
(17, 24), and from the data of the present

—4—


DEEP RENAL 100 — =

PRESSURE
(mm Hg)

RENAL
ARTERY
PRESSURE

(mm Hg)

mm Hg /cc/ min

VEIN

5sO-

+
0.61
Ro-y 0.40 0.39
Ry 0.2! 0.18

RBF = 5.5 cc/min/gm (RAP = 128 mm Hg)

Figure 2, Relationships of deep renal vein pressure, renal artery pressure. and renal segmental
resistance.

(one expt.)

R,=TOTAL RESISTANCE (RAP/F) ‘LVP=ZsRO mm Hg)
R,~y=PRE-VENOUS SEGMENT RESISTANCE (RAP-DVP/F)
R,=VENOUS SEGMENT RESISTANCE (DVP—LVP/F)

—7—


C03 417

MECHANISM OF AUTOREGULATION
IN THE INTACT KIDNEY

LERNER B. HINSHAW
THOMAS E. EMERSON, Jr.
CHARLES M. BRAKE
(With the assistance of Martha S. Brown and Frederick D. Masucci)

Renal Physiology Section
Environmental Physiology Branch

IT p Fi po Lee

by. ey

63-32

FEDERAL AVIATION AGENCY
CIVIL AEROMEDICAL RESEARCH INSTITUTE
AERONAUTICAL CENTER

OKLAHOMA CITY, OKLAHOMA
DECEMBER 1963


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TABLE I

EXTRAVASCULAR PRESSURE AND ARTERIAL
PRESSURE IN THE INTACT KIDNEY
(21 KIDNEYS, 21 DOGS)

EXTRAVASCULAR MEAN ARTERIAL RENAL BLOOD FLOW
PRESSURE* (mm Hg) PRESSURE (mm Hg) ({cc/min./gm)
MEAN 37 122 4.0
RANGE 18-50 90-145 2.3-5.5
S. E. 2 3 0.2

“Determined by two to four procedures described in text. in 17 kidneys,
Determined by value of deep vein pressure in 4 kidneys.

TABLE I

DEEP VEIN PRESSURE AND RENAL ARTERY
PRESSURE IN INTACT KIDNEYS*

EXPT. NO. DEEP VEIN PRESSURE RENAL ARTERY PRESSURE
(mm Hg) (mm Hg)
13 . 45 123
14 37 145
15 37 128
16 61 151
7 45 13]
18 24 11¢
19 50 140
20 41 109
21 41 128
MEAN 42 129

*Pressure recorded early in experiment at time of equilibrium of renal blood flows.
(Average RBF = 4.2 cc./min./gm.; range, 2.7-5.5)


PLACEMENT OF DEEP VEIN CATHETER
IN INTACT KIDNEY

CATHETER TIP
IN DEEP VEIN

RENAL VEIN

~s aa Saa PLASTIC CANNULA

ieee RUBBER TUBING

wroee NEEDLE (No. 13)
/
VENOUS

OUTFLOW Qe

INTO RESERVOIR ----TO PRESSURE

TRANSDUCER

Ficure 1. Placement of deep vein catheter in intact kidney.

—6—


pump. Renal vein outflow was measured with
cylinder and stop watch. Large renal vein pres-
sure, lissue pressure (needle pressure) and
aortic pressure (orifice renal artery pressure)
were measured via pressure transducers and re-
corded on a Sanborn recorder, as previously
described (8-12). Twenty-three intact kidney
preparations were carried out as described
above. Renal blood flows averaged 4.0 cc/min./
gm. (range, 2.3-5.5) at an average renal artery
pressure of 122 mm. Hg (range, 90-155).
Several dog-pump-perfused isolated kidney
studies were also carried out to determine the
effect of bilatera! carotid occlusion on levels of
blood borne vasoactive agents. Deep vein pres-
sures in some intact kidneys were obtained as
illustrated in Figure 1. The tip of a flexible
polyethylene catheter was carefully maneuver-
ed deeply into the kidney substance at the level
of the arcuate or interlobular veins. Criteria for
successful catheter tip placement were (a) a
marked increase in pressure when the catheter
tip was advanced into veins deep within the
renal substance (b) a rapid return in pressure
following catheter flushing, and (c) free with-
drawal of blood through the catheter. Technical
errors inherent in the procedure have been
described in two reports. (13, 16). Large vein
pressure was measured and maintained at zero
mm. Hg. In some experiments iarge vein pres-
sure was increased in steps by adjustment of a
screw clamp placed on the venous outflow cath-
eter distal to the pressure measuring needle.
Tissue pressure was estimated by four inde-
pendent procedures: (a) value of deep vein
pressure, (b) value of needle pressure,
(c) value of increased large vein pressure ze-
sulting in a detectable fall in renal blood ilow,
and (d) value of increased ureteral pressure
bringing about a detectable decrease in renal
blood flow. As in previcus studies (11, 13-16),
these values showed close agreement.
Systemic arterial pressure in some experi-
ments was increased by transfusion or decreased
by withdrawal of blood following transfusicn.
Results were compared to those in which arieri-
al pressure was increased by bilateral carotid
artery occlusion as carried out by Thurau and
Wober (26). Experiments on the dog-pump per-
fused kidney were also carried out to assay

levels of circulating constrictor agents following
carotid artery occlusion.

RESULTS

Experiments were carried out in intact dog
kidneys to obtain estimations of extravascular
pressure (tissue pressure). Table IJ provides
average values of systemic arterial pressure
(orifice renal artery pressure) and extravascu-
lar pressure in twenty-one intact kidney pre-
parations. Extravascular pressure values were
obtained either by deep vein pressure measure-
ment (4 kidneys )er by values obtained from
two to four of the independent procedures de-
scribed in the Methods section. Pressures in
twenty-one kidneys averaged 37 mm. Hg (range,
18-50) at an average orifice renal artery pres-
sure of 122 mm. Hg (range, 90-145). Renal
blood flows averaged 4.0 cc./min./gm. (range,
2.3-5.5).

Deep vein pressures, obtained as described in
Figure I, were measured early in nine intact
kidneys. This data with simultaneously measur-
ed renal artery pressures is shown in Table II.
Deep venous pressure averaged 42 mm. Hg in
nine kidneys with an average renal artery pres-
sure of 129 mm. Hg (mean renal blood flow,
4.2 cc./min./gm.).

As an extension to the above experiments,
systematic arterial pressures were increased in
some experiments by transfusion of blood, or
decreased following transfusion. The effect of
the resulting change in renal artery pressure on
extravascular pressure was determined. Figure
2 provides raw and calculated data from one
intact kidney experiment. It is seen that the
change in total renal vascular resistance
(RAP/F) was accounted for in large measure
by alterations in venous segment resistance
(DVP-LVP/F) (deep vein pressure minus large
yein pressure/blood flow). Table Ii summar-
izes results from 7 intact kidney experiments.
Arterial pressure is increased from an average
of 101 to 155 mm. Hg and autoregulation is
observed in each instance, Approximately two-
thirds of the increase in total renal resistance
(RAP/F) was accounted for by alterations in
venous segment resistance (DVP-LYP/F).
These data emphasize the role of extravascular
pressure changes as an important component of
the autoregulatory apparatus.

—2—


Con

MECHANISM OF AUTOREGULATION
IN THE INTACT KIDNEY

LERNER B, HINSHAW
THOMAS E. EMERSON, Jr.
CHARLES M. BRAKE
(With the assistance of Martha S. Brown and Frederick D. Massuci)

ABSTRACT

The mechanism of rena! autoregulation is unclear. The subject of the present investi-
gation is the mechanism of autoregulation of blood flow in the intact kidney. The left
kidney of the anesthetized dog was exposed via a flank approach. Renal venous outflow
was measured during control periods and following separate elevations of renal artery
pressure, renal vein pressure, and ureteral pressure. Extravascular pressure (tissue
pressure) was estimated by obtaining values of (a) deep vein pressure; (b) needle pres-
sure; (c) and (d) large vein pressure and ureteral pressure elevations resulting in signifi-
cant decreases in renal biood flow. Results are in agreement with previously reported
studies regarding the important role of extravascular pressure in autoregulation. Increases
in renal artery pressure result in elevations of extravascular pressure which compress
the renal vasculature. Increases in renal vein and ureteral pressures do not decrease renal
blood flow until approximating or exceeding resting tissue pressure. Results from carotid
artery occlusion experiments indicate that extrarenal humoral influences may be super-
imposed on the autoregulatory phenorienon.

Recent studies have accounted for autoregu-
lation of renal blood flow on the basis of
changes in extravascular pressure (1, 8-15, 21-
22). Experiments carried out in this laboratory
(8-15) have been concerned with autoregula-
tion of flow in isolated perfused kidneys. The
question has arisen as to the applicability of
these findings to the intact kidney. The present
investigation is therefore a logical extension of
the earlier studies to explore the possible in-
trinsic renal mechanism(s) operating within
the intact dog kidney which would account for
blood flow regulation. Results from the present
work are in agreement with previcusly reported
isolated perfused kidney studies (8-15) regard-
ing the important role of extravascular pressure
in the autoregulatory phenomenon.

METHODS

Adult dogs were intravenously anesthetized
with sodium pentobarbital, 30 mg./kg. The left

kidney was exposed via a flank incision, care
taken to avoid penetration of the peritoneal lay-
er. The kidney was carefully freed from the per-
itoneal lining, the artery, vein, and ureter were
cleared of all extraneous tissues. No ties were
placed around the kid aey in the region of the hi-
lus. Several blood vessels were ordinarily ligated

in the anterior polar region of the capsule. The
kidney was denervated surgically by section of
nerve fibers. and chemically, by placing a gauze
saturated with procaine around the renal
pedicle. Following heparinization of the dog (3
mg./kg. body weight), the renal artery was
temporarily ligated to permit cannulation of the
renal vein with a large bore polyethylene tub-
ing. Renal venous outflow was collected in a
plastic reservoir secured in a water bath and
blood returned from the kidney to the femoral
vein of the dog by means of a sigmamotor

—1—



FOREWORD

The kidney performs a crucial role in maintaining a stable environ-
ment for the various tissues and organ systems in the body. A great variety
of extrinsic (extrarenal) factors are involved in the interplay between the
kidney and its environment. Among these, neurohumoral influences, are
of chief importance in various stress states. Some of these have been evalu-
ated in a previous CARI report from this laboratory. Man in flight may
encounter environmental conditions which markedly affect renal hemo-
dynamics. Normally, extrarenal controlling influences, such as the carotid
sinus apparatus, are involved in regulating the vascular resistances of
important beds such as the kidney. The kidney is unique, however, in its
peculiar intrinsic ability to control its own blood flow rate. This poorly
understood characte-istic, termed “autoregulation,” has been under inten-
sive study for over a half century. The present investigation is of crucial
importance in that it is concerned with the mechanism of autoregulation in
the intact kidney, and relates the roles of extrarenal humoral influences
as modifying factors of the basic autoregulatory apparatus. These experi-
ments serve to reveal the important links between intrinsic - extrinsic con-
trolling mechanisms in renal hemodynamics operative in man during con-
ditions of stress.



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