Pressure regulation in muscle of unanesthetized bats

MICROVASCULAR

RESEARCH

33, 315-326 (1987)

Pressure Regulation

in Muscle of Unanesthetized

Bats’

DICK W. SLAAF,* ROBERTS. RENEMAN,? AND CURT A. WIEDERHIELM Department of Physiology and Biophysics, UniversiQ of Washington, Seattle, Washington 98195, and Departments of *Biophysics and fPhysiology, University of Limburg, Maastricht, The Netherlands Received October 4, 1985 In unanesthetized bats direct microvascular pressure measurements were made in the tensor plagiopatagii muscle without surgical intervention. Pressure recordings showed great variability due to vasomotion and other physiological stimuli, but were in the same order of magnitude as described in muscle of other species in the anesthetized state. A substantial part of the pressure gradient is dissipated at the level of the small arterioles. Arterial pressure was changed by depressurizing a box containing the body of the bat, while the muscle was under atmospheric condition. In all larger arterioles and in 12 of 19 smaller arterioles a linear relation existed between microvascular pressure and box pressure. Of 19 small arterioles, 7 exhibited a clear biphasic regulatory response to a decrease in arterial pressure. The data are discussed in relation to different models of regulation. o 1987 Academic Press. Inc.

INTRODUCTION Literature provides evidence that flow through the vascular bed of an organ tends to be maintained during reduction of arterial pressure due to a decrease in resistance of precapillary vessels (Johnson, 1980). Evidence has been presented in favor of a myogenic component and a metabolic component in this regulation (Bouskela and Wiederhielm, 1979; Burrows and Johnson, 1981, 1983; Borgstrom ei al., 1981; SulIivan and Johnson, 1981; Mortf and Granger, 1983). A consequence of maintained flow through the capillary and venular bed should be maintenance of capillary pressure and, hence, an unchanged capillary exchange. Evidence of regulation of cap&u-y pressure has been obtained indirectly (Johnson and Hanson, 1962; J%rhult and Mellander, 1974). Direct microvascular pressure measurements performed under anesthesia in a variety of tissues in diierent animals demonstrated that microvascular pressures throughout the arteriolar bed changed in proportion to the changes in arterial pressure (Gore, 1974; Gore and Bohlen, 1975; Bohlen and Gore, 1977; Burrows and Johnson, 1981; House and Johnson, 1983). Gore (1974) observed an apparent constancy of capillary pressure during changes in systemic blood pressure, but suggested that this was primarily the consequence of vascular geometry peculiar to the mesentery. House and Johnson (1983) reported stability of pressure in 4” venules and suggested that the pressure gradient in ’ Supported by NIH Grant 16910. Dr. Slaaf was the recipient of a fellowship of The Netherlands Organization for the Advancement of Pure Research (ZWO). 315 0026-2862/87 $3.00 Copyright Q 1987 by Academic Press, Inc. All rights of reproduction in any form reserved. Printed in U.S.A.

316

SLAAF,

RENEMAN,

AND

WIEDERHIELM

the venous network and the pressure in capillaries of skeletal muscle may be maintained during arterial pressure reduction. The present experiments were designed to measure the microvascular pressure distribution throughout the vascular bed supplying and draining a muscle and to assess its dependence on reduction of arterial pressure in the bat Tudurida brasiliensis mexicana (Wiederhielm et al., 1979) without surgery or anesthesia. Arterial (and transmural) pressure is varied by placing the body of the animal in a box and lowering the pressure in the box, and hence in the animal, while the wing with the tensor plagiopatagii muscle (Wiederhielm and Slaaf, 1987) remains outside the box under atmospheric pressure. METHODS The experiments were performed on 27 intact unanesthetized Mexican freetailed bats (Tuduridu brasiliensis mexicana) of either sex, ranging in weight from 10 to 20 g and kept in a chronic colony. During the experiments the body of each bat was kept in an airtight box, while the wing with the muscle under observation was stretched out through a slit in the bottom of the box and extended over a glass sheet for microscopic observation. A bead of silicone putty prevented leakage of air through the wing slit. Application of negative pressure to the box had the same effect as lowering arterial and hence transmural pressure, while venous pressure remained close to atmospheric due to vascular waterfall effects (Wiederhielm et al., 1979). The tensor plagiopatagii muscle used for the experiments is located in the trailing edge of the wing web between the body and the fifth finger (Wiederhielm and Slaaf, 1987). The vasculature supplying and draining the muscle originates from an arcading system running between the leg and the upper arm (Fig. 1). This arcade gives off a first-order arteriole-venule pair running more or less parallel to the muscle and supplying and draining the lower part of the web and the muscle. Second-order arterioles and venules run between these main vessels and the muscle. These arterioles may bifurcate several times before they supply an arcading system in the muscle, formed by the arcuate arterioles, running parallel to the muscle. Transverse arterioles run across the muscle, sending off branches that penetrate the muscle and that break up into capillary networks. The capillary networks join to form transverse venules which collect into arcuate venules. The venular arcades are drained by second- and first-order venules that lead to the veins. Observations were made by means of an A0 Microstar microscope using a Leitz UMK 50 (N.A. = 0.40) long working distance objective lens in combination with an A0 achromatic condenser (N.A. = 1.40) in critical illumination. Both surfaces of the wing were coated with a thin layer of mineral oil to reduce mobility of the wing and light scattering in the stratum corneum of the skin. Intraluminal pressures in the microvascular bed were recorded continuously by means of a micropipet servonulling system (Wiederhielm et al., 1964; Wederhielm and Weston, 1973) in 24 animals. Micropipets were filled with a 2 M NaCl solution and had resistances varying between 5 and 10 M fl (FOX and Wiederhielm, 1973). The zero-pressure reference level was established prior to each pressure recording and checked afterward. Insertion of the micropipets,

PRESSURE

REGULATION

IN

317

MUSCLE

1st order 2nd order

tensor

plagiopatagii

FIG. 1. Schematic representation of the vasculature supplying and draining the tensor plagiopatagii muscle. Note the dual input for the arcuate and transverse arterioles.

using a Fonbrune pneumatic micromanipulator, usually did not provoke spontaneous vascular activity, but could lead to local constriction or vasodilation. After penetrating the blood vessel the tip of the micropipet was moved as close to the wall as possible to avoid interference with flow. Artifacts generated by contact with the wall can easily be detected since the pipet impedance increases to high values, reflected in a pronounced increase in pressure within the servosystem (Wiederhielm et al., 1964). Directly after sealing the box vasodilation could often be observed throughout the vascular bed. This dilation generally disappeared within the resting period. Sometimes, especially when small vessels were impaled, the vasculature in one arcading section of the muscle remained dilated due to local manipulative trauma. Data from these dilated vessels were discarded. In these instances we moved our recording pipet to another vessel at least two arcades away, to minimize an artifactual influence. In preparations with a regular flow pattern an elevated venous pressure was never observed. Pressures were expressed as the mean (F) during the stable part of the experimental period and the deviation from this mean, discarding extreme, nonconsistent variations (see Fig. 2). The duration of the pressure recordings ranged from 1 min to several hours. In a separate series of three experiments microvascular diameters were measured as a function of Ph,. Inner vascular diameters were measured from a videomonitor using a calibrated pair of calipers. Data are presented as means 2 SD, with number of measurements in parentheses. Experimental protocol. Initially the bat was allowed to rest for approximately one-half hour in a slightly (3-5 mm Hg) pressurized box. A small controllable

318

SLAAF, RENEMAN,

AND WIEDERHIELM

mmHg 100

50 0 0

12

3

4

5

6

7

8

9

heart constant ZE

limits

box

pressure:

of pressure

Pbox = f5

rate

10 minutes 240/min.

mmHg ji

variation

deviation

=

=

Pmax +

Prnin

= 69 mmHg

P,,X

prnin

= 11 mmHg

2

2

FIG. 2. Typical microvascular pressure recording from a first-order arteriole.

leak on top of the box prevented buildup of CO* or depletion of OZ. When a proper pressure recording was obtained, box pressure (Pbox) was set close to atmospheric (= zero) pressure. After a control period of at least 2 min successive negative pressure steps were applied varying between 7 and 25 mm Hg. Each step varied in duration from 1 to more than 5 min to attain a new “stable” pressure level. Pbox was decreased until flow stopped or as long as a proper recording could be obtained. Hypothetical pressure relations. The result of a stepwise change in Pboxdepends on the regulating properties of the vascular tree. If the vessel tree acts as a rigid system pressure changes will not affect the distribution of resistance within the vascular bed. A change in Pbox and, thus, in arterial pressure will result in a proportional change in all microvessel pressures (Fig. 3A). The family of linear relations has an intercept at zero pressure. The proportionality factor is defined asa! = AP vessel/APbox. If, however, autoregulation occurs in a vessel tree capillary pressure will remain constant over a certain pressure range. Two different types of myogenic autoregulation may be discerned: a homogeneous myogenic behavior of the arteriolar network or a series-coupled myogenic reaction. In case of a homogeneous myogenic response, flow can be maintained by the evenly distributed C

FIG. 3. Hypothetical relations tube system: all relations coincide are initially linear with an intercept network: a typical plateau relation

between arteriolar pressures and box pressure applied. (A) Rigid with a straight line. (B) Homogeneously dilating vessels: relations close to capillary pressure. (C) Series-coupled myogenic arteriolar is seen, which is longer the lower the initial pressure.

PRESSURE

REGULATION

IN

MUSCLE

319

reduction in resistance in the precapillary bed. The unchanged flow through the capillary and venous bed should result in a maintained capillary pressure. This may result in linear relations between box pressure and arteriolar pressure, but with an intercept of this family of relations close to capillary pressure (Fig. 3B). It should be noted that in this case only capillary pressure is regulated. In case of a series-coupled myogenic reaction small reductions in arterial pressure will induce dilation in the larger arterioles, which restores pressure in the smaller arterioles and the capillaries to the normal level. There will be no persistent pressure stimulus in the vessels downstream of the dilated ones and, hence, their diameter does not change. With greater pressure reduction further dilation of the larger arterioles is not possible anymore, so that downstream pressure cannot be restored to its normal value and, hence, small arterioles will dilate due to a decrease of the local pressure (Johnson et al., 1978; Johnson, 1980) (Fig. 3C). At any level in the vascular tree pressure can be maintained by upstream regulation until arterial pressure reduction has caused maximum dilation in all upstream vessels. The relation between PboXand Pmicrovesse, will be biphasic. The proportionality factor (Ywill be small for the initial steps in PbX and will increase during consecutive steps until a new stable value is attained. In the smallest precapillary vessels, however, the series-coupled and homogeneous myogenic reactions are similarly related to box pressure and cannot be distinguished (Figs. 3B and 3C). For all relations between microvascular pressure and box pressure the proportionality factor was calculated from the initial slope of the APvesse,/APbox plot, resulting in (.y,, and from the mean slope ((Y). If (Y, was less than 50% of (Y, the relation was considered to be that of a series-coupled myogenic vessel tree. For arterioles exhibiting a linear response it is possible to calculate arterial pressure (P3 at the entrance of the box from the microvascular pressure and the proportionality factor. In case of a homogeneous regulatory response it holds that P, = [(Pmicrovessel - P&/a] + Pcap, where Pcap = capillary pressure at the arteriolar side. For a rigid system it holds that P, = Pmicrovessel/(Y. RESULTS Control

Pressure

Distribution

The pressure recordings obtained from all arteriolar vessels showed cardiac pulsations of a few millimeters Hg. Superimposed on these pulsations slower (ir)regular changes in pressure associated with vasomotion were seen. Figure 2 shows a typical recording obtained from a first-order arteriole. Mean arteriolar pressure was 69 mm Hg, whereas the change induced by vasomotion activity was 1I mm Hg. The two large peaks at 2 and 9 min regularly occurred at this interval over a period of more than 1 hr. Transverse arterioles generally receive their flow from both sides of the supplying arcade. In some experiments, however, the transverse arteriole was supplied from either side of the arcade in an alternating way, resulting in marked changes in the pressure recordings (Fig. 4A). In other experiments a transverse arteriole showed strong vasomotion at its origin, resulting in periods of low flow and marked dips in the pressure recordings (Fig. 4B). At the venular side of the vascular bed, slow and low frequent venomotion was observed. The associated pressure changes occurred in the first-order venules

320

SLAAF,

RENEMAN,

AND

WIEDERHIELM

A

B

mmHg 75

#51

mmHg

,I\L . .

25 t. v 50 0 0

# 1 min. P,,.-drnx

#2*

75

I 2

25 500 1 y-z--y 0 min.

1

P box z - 66mmHg

FIG. 4. Microvascular pressure recordings from two transverse arterioles. (A) Flow into transverse arteriole varied from left (L)- to right (R)-hand side of arcade. (B) Strong vasomotion at the origin of the transverse arteriole caused marked dips in the pressure recordings.

and down to the transverse venules. The amplitude of this pressure change was relatively small, varying from 1 to 5 mm Hg. The results of 106 micropunctures in the microvascular bed supplying and draining the tensor plagiopatagii muscle are shown in Fig. 5. Data are grouped according to microvessel level, rather than to diameter (Wiedeman et al., 1981). A considerable pressure drop occurred between first-order and transverse arterioles. A substantial fraction of the remaining pressure gradient was dissipated in the transverse arterioles and precapillary vessels. Only a small pressure drop of approximately 6 mm Hg occurred between transverse and first-order venules. Microvascular

Pressures as a Function of Reduced Box Pressure

When a stable microvascular pressure recording was obtained, Pb, was reduced stepwise. Figure 6 shows a recording as obtained from an arcuate arteriole (P,,,) and the concomitant recording of Pbox. The control pressure fluctuated between 50 and 65 mm Hg. The first step in Pbox (- 15 mm Hg) resulted in a transient pressure drop followed by restoration of pressure and vasomotion. The step from - 28 to - 41 mm Hg resulted in a significant decrease in P,,, and with subsequent ioomicrovascular pressure

(mmHg)

75

50-

FIG. 5. Results of 106 micropunctures. Data are grouped at the microvessel level. Mean values are indicated by dots, standard deviations from the mean by vertical bars, and average deviation from the mean during a recording by the cross-hatched area. The number of measurements obtained at each site is indicated.

PRESSURE REGULATION

321

IN MUSCLE arcuate

microvascular pressure mmHg

50-65

time -500 -100

limits

r

’

:

’ 50-65

’

of pressure 47-62

arteriole mmHg

variation

’

42-52

’

30-35

’

22-27

’

:

E”

5-l

‘box mmHg

0

i

,

in’

-15

-;,~!,,_Ib

,

’

-26

, box

FIG. 6. Microvascular in PboX (bottom tracing).

-41

,

li

-55

m’ln.

,

pressure

-67

i4

,

mmHg

pressure recording (top tracing) from arcuate arteriole during reductions

steps the vasomotion pattern almost disappeared. Figure 7 shows a graphic representation of the recording in Fig. 6. Figure 8 shows the typical linear response of a first-order arteriole and the regulatory, albeit linear, response of an arteriolar capillary. In Fig. 9 the responses in four different vessels exhibiting relations from a homogeneously dilating vessel tree are presented. Both arteriolar responses are linear. Pressure in the first-order venule approaches atmospheric pressure, whereas pressure in the arcuate venule remains at 6-7 mm Hg. When Pbox was reduced the first step in pressure resulted in the relatively largest decrease in venular pressure. Further decreases in PbOXhad a negligible influence on venous pressure. Table 1 summarizes the results of all pressure recordings in arterioles as a function of PbOX. For each pressure run it was decided, by comparing (Ywith cr,, whether the resulting relative pressure change was linear. The results were classified accordingly. Classification of both responses in arteriolar capillaries is not possible since both possible mechanisms have the same response. Table 2 summarizes the results for all venules. Mean venular pressures and minimal

pressure

,5 _

(mmHg) arcuate

arteriole

25- - -

rigid tube

expected

\\ ‘\

respo”se o-

, 0

‘d,

I

I

-25

,

-50 ‘box

-75

I -100

@mHg)

FIG. 7. Graphic representation of the two tracings presented in Fig. 6. The solid vertical bars represent the fluctuations of the pressure. The dashed lines represent the expected nonregulating response in the arcuate arteriole in case of a rigid tube system. The arrow indicates that, after an initial drop, P,, rose to the values as represented by the bar. In this particular experiment a, = 0.0.

322

SLAAF,

RENEMAN,

AND

WIEDERHIELM

loo# 57 microvascular press”re (mmf-b)

first

arteriolar o-

, 0

order

capillary

I

,

-50

-25

pressures

-75

r

(mm&U

‘box

FIG. 8. Graphic representation of microvascular capillary during reduction of Pbox.

arteriole

of a first-order

arteriole

and an arteriolar

venular pressures, as attained during a pressure run, are presented. Initial relative changes in venular pressure ranged between 0.4 and 0.8 for small pressure steps. In three animals microvascular diameters were measured as a function of Pbox throughout the arteriolar tree. All vessels dilated as a result of a decrease in Pk,,. The strongest relative dilation occurred in the arcuate and transverse arterioles. There was no clear relation between the pressure level at which dilation started and the type of the vessel under observation (Table 3).

microvascular pressure

(mmHg)

50-

25-

o-

,

t .50

1

FIG. 9. Graphic representation of microvascular exhibiting linear arteriolar responses.

-25

-50

pressures

I

as a function

I

-75

of Pbox for a vessel

tree

PRESSURE REGULATION TABLE RESULTS

OF PRESSURE

RECORDINGS

323

IN MUSCLE

1

IN ARTERIOLES

AS A FUNCTION

OF

Pbox

Relative pressure change Mean Pressure (all vessels)

Vessel type First-order arteriole Second-order arteriole Arcuate arteriole Transverse arteriole Arteriolar capillary

75.2 58.3 48.8 45.8 29.3

k 11.5 2 12.1 I!T 9.4 f 6.6 iz 1.7

Biphasic cy,,

Linear OL

(29) (9) (16) (7) (4)

0.83 0.74 0.50 0.49

2 zt 2 t

0.08 (18 0.24 (7) 0.24 (7) 0.12 * 0.05 (3) 0.15 (3) 0.12 IT 0.05 (4) 0.10 ‘- 0.03 (2)

Note. Relative pressure changes (proportionality factor) are grouped according to a linear or an autoregulatory response. Number of measurements is within parentheses. Data are presented as means f SD. a Response was linear, but regulating (see Results).

DISCUSSION Microvascular pressures recorded in the bed supplying and draining the tensor plagiopatagii muscle in the bat wing showed great variability due to vasomotion and other physiological stimuli in the unanesthetized intact bat. In this respect the recordings differ from the rather stable recordings reported in anesthetized tissues. The distribution of microvascular pressures in this muscle shows close agreement with that obtained in the connective tissue between the third and fourth fingers of the same species (Wiederhielm and Weston, 1973). The firstorder arterioles, as investigated in the present study, however, not only supply the muscle with blood, but also supply blood to the connective tissue in that part of the web. The pressure distribution shows the same characteristic as the one assessed by Fronek and Zweifach (1975, 1977) in the tenuissimus muscle of the cat, i.e., the major pressure drop occurs in the smaller arterioles. The pressure distribution in skeletal muscle differs considerably from that found in cat mesentery (Gore, 1974; Zweifach, 1974) or rat intestine (Bohlen and Gore, 1977; Gore and Bohlen, 1977), where the major pressure drop occurs in the larger arterioles. The changes in arteriolar diameter resulting from the application of negative box pressures showed good agreement with those recorded earlier in the same species by Bouskela and Wiederhielm (1979). Since all vessels dilated in response to a decrease in Pbox,no definite conclusions can be drawn in favor of a rigid TABLE RESULTS

OF PRESSURE

IN VENULES

Mean pressure

Minimal pressure

(mm Hg)

(mm W

Vessel Transverse venule Arcuate venule Second-order venule First-order venule

2

RECORDINGS

16.0 14.2 12.9 9.6

* + ” k

3.0 2.6 2.9 1.7

(n (n (n (n

= 3) = 7) = 5) = 22)

8.5 6.8 6.8 2.0

(7-10, (4-9, (2-9, (O-4,

n n n n

= 2) = 5) = 4) = 17)

Nofe. Mean pressures and minimal pressures during a pressure run are given. n = Number of measurements. Within parentheses is the range of minimal pressures.

324

SLAAF,

RENEMAN,

AND

TABLE

DIAMETERS,

WIEDERHIELM

3

EXPRESSED AS A PERCENTAGE OF THE CONTROL VALUE, NEGATIVE Box PRESSURE

AS A FUNCTION OF APPLIED

Pbox -15 mm Hg First-order arteriole” Second-order arteriole Arcuate arteriole Transverse arteriole

100; 112 2 104 2 100 f

-25mmHg

-4OmmHg

-55mmHg

-7OmmHg

118 106; 127 148; 132 171; 141 174; 149 15 (5) 123 5 25 (5) 134 f 28 (4) 138 ? 25 (4) 152 k 32 (4) 15 (5) 127 ? 15 (5) 175 2 29 (5) 187 k 38 (5) 217 2 44 (4) 8 (4) 134 f 37 (4) 161 f 31 (4) 197 + 14 (4) 240 +- 25 (3)

Note. Number of measurements is within parentheses. Data are presented as means 2 SD. ’ Only two measurements are given.

system or a series-coupled myogenic reaction. If, however, the regulation of flow is incomplete, any relation between Figs. 3A, 3B, and 3C can be found. The relation between applied (negative) box pressures and microvascular pressures, as assessed in first- and second-order arterioles, was linear in all cases, whereas linearity occurred in only I2 of 19 small arterioles. It should be noted that vessels exhibiting prolonged vasodilation upon impalation with the micropipet or as a result of sealing of the box were discarded. Seven small vessels exhibited a biphasic response (Fig. 7 and Table 2) indicative of a partially series-coupled myogenic reaction. Calculation of arterial pressure at the entrance of the box, using the mean pressure (75 mm Hg) and mean proportionality factor (0.83) of the first-order arterioles and the precapillary pressure as measured (Table l), leads to arterial pressures of 85 and 90 mm Hg for a homogeneously regulatory response and a rigid system, respectively. As expected, the influence of regulation at this level is limited. In case of second-order arterioles, extrapolated arterial pressures of 68 and 79 mm Hg were found. In the arcuate and transverse arterioles, where microvascular pressure and the proportionality factor are almost the same, the extrapolated arterial pressures were 62 and 96 mm Hg, the latter being the extrapolated value for a rigid system. The arterial pressures, as found by extrapolation using the rigid tube concept, tend to stay closer together than those calculated using the homogeneous regulation concept. Since all arterioles actually dilated, this means that the regulatory response was not sufficient to maintain capillary pressure. The average proportionality factor for the biphasic responses in the smallest vessels was approximately 0.10, which is a factor of 3 to 5 smaller than expected from the relative control pressure in case of nonregulatory responses and complies with both regulating models. That both linear and biphasic responses occur, combined with the fact that all arterioles dilate following reduction in arterial pressure, is indicative of a partial regulatory response. Evidence for a regulatory response maintaining capillary pressure has been obtained by Johnson and Hanson (1962) from isogravimetric experiments. Arterial resistance decreased as arterial pressure was reduced in 70% of the experiments. In some of these experiments arterial pressure could be changed over a range of 90-120 mm Hg without any apparent change in capillary pressure, when venous pressure was kept constant. In most experiments, however, venous pressure had to be increased to counterbalance the influence of a reduction in arterial pressure

PRESSURE

REGULATION

IN

MUSCLE

325

at the capillary level due to the incompleteness of autoregulation. That only part of the experiments showed regulation of capillary pressure is observed in both the isogravimetric experiments and our direct pressure measurements in the intact unanesthetized muscle of the bat. The cause for this might be differences in reactivity. Direct microvascular pressure measurements in other tissues revealed linear relations between central pressure and microvascular pressure with intercepts near zero pressure. Gore and Bohlen (1975) and Bohlen and Gore (1977) found this linear relation in a preparation that constricted following pressure reduction, whereas Burrows and Johnson (1981) found a linear relation in the presence of vascular dilation. Gore reported that in some capillaries, although the relations were linear, pressure was maintained. He explained these findings by redistribution of how in a multiple-input capillary bed, rather than by a true regulatory mechanism. Such an explanation could also hold for the present muscle preparation since arcuate arterioles receive blood flow from second-order arterioles on both sides of the arcade (Fig. 1). The possible influence of this is shown in Fig. 4A. If flow comes from another side of the arcade when flow is reduced, preservation of microvascular pressure might occur at the level of the arcuate arterioles and, hence, down to the arteriolar capillaries merely as a result of flow redistribution. Micropressure at the venular side tends to be maintained after the initial drop in venous pressure down to atmospheric pressure. First-order venular pressure drops to almost atmospheric pressure, but pressures in the smallest venules remain at a level of about 10 mm Hg even at very low box pressures. The pressure difference between the various venular vessels remains almost constant during these pressure runs. In arterial occlusion experiments House and Johnson (1983) reported linear responses in all (arteriolar and venular) vessels with an intercept close to venous pressure, except for fourth-order venules, where the intercept was about 15 mm Hg. Our data suggest that venular pressure is maintained more evenly. The present data indicate that, although all arterioles dilate during a reduction of perfusion pressure, maintenance of microvascular pressure is incomplete. The data do not comply with the series-coupled myogenic theory. The results might be explained by a homogeneous dilation, resulting in partial autoregulation, or by redistribution of flow. ACKNOWLEDGMENTS The authors are greatly indebted to Ms. Rosy Hanssen The skillful assistance of Mr. Robert Heald, Mr. Louis acknowledged.

for her help in preparing the manuscript. Stamps, and Dr. J. Bassett is gratefully

REFERENCES BOHLEN, H. G., AND GORE, R. W. (1977). Comparison of microvascular pressures and diameters in the innervated and denervated rat intestine. Microvasc. Res. 14, 251-264. BORGSTR~M, P., GR~NDE, P.-O., AND LINDBOM, L. (1981). Responses of single arterioles in vivo in cat skeletal muscle to change in arterial pressure applied at different rates. Acta Physiol. Scand. 113, 207-212. BOUSKELA, E., AND WIEDERHIELM, C. A. (1979). Microvascular myogenic reaction in the wing of the intact unanesthetized bat. Amer. J. Physiol. 237, H59-H65.

326

SLAAF,

RENEMAN,

AND

WIEDERHIELM

BURROWS,M. E., AND JOHNSON,P. C. (1981). Diameter, wall tension, and flow in mesenteric arterioles during autoregulation. Amer. J. Physiol. 241, H829-H837. BURROWS,M. E., AND JOHNSON,P. C. (1983). Arteriolar responses to elevation of venous and arterial pressures in cat mesentery. Amer. J. Physiol. 245, H7%-H807. Fox, J. R., AND WIEDERHIELM, C. A. (1973). Characteristics of the servo-controlled micropipet pressure system. Microvasc. Res. 5, 324-335. FRONEK, K., AND ZWEIFACH, B. W. (1975). Microvascular pressure distribution in skeletal muscle and the effect of vasodilation. Amer. J. Physiol. 228, 791-796. FRONEK, K., AND ZWEIFACH, B. W. (1977). Microvascular blood flow in cat tenuissimus muscle. Microvasc. Res. 14, 181-189. GORE, R. W. (1974). Pressures in cat mesenteric arterioles and capillaries during changes in systemic arterial blood pressure. Circ. Res. 34, 581-591. GORE, R. W., AND BOHLEN, H. G. (1975). Pressure regulation in the microcirculation. Fed. Proc. 34, 2031-2037. GORE, R. W., AND BOHLEN, H. G. (1977). Microvascular pressures in rat intestinal muscle and mucosal villi. Amer. J. Physiol. 233, H685-H693. HOUSE, S. D., AND JOHNSON,P. C. (1983). Relationship between pressure gradient and flow in the venous network of sketetal muscle. Microvasc. Res. 25, 238. J~RHULT, J., AND MELLANDER, S. (1974). Autoregulation of capillary hydrostatic pressure in skeletal muscle during regional arterial hypo- and hypertension. Acta Physiol. &and. 91, 32-41. JOHNSON,P. C. (1980). The myogenic response. In “Handbook of Physiology: Section 2. The Cardiovascular System” (D. F. Bohr, A. P. Somlyo, and H. V. Sparks, Jr., Eds.), F’ubl. Amer. Physiol. Society, Bethesda, Maryland, pp. 409-442. Williams & Wilkins, Baltimore. JOHNSON, P. C., BURROWS, M. E., SULLIVAN, S. M., AND LALONE, B. J. (1978). Series-coupled myogenic behavior of the arteriolar network. In “Abstract-book,” XIth Conf, Europ. Sot. Microcirc., Cagliari, p. 79. JOHNSON,P. C., AND HANSON, K. M. (1962). Effect of arterial pressure on arterial and venous resistance of intestine. J. Appl. Physiol. 17, 503-508. MORFF, R. J., AND GRANGER, H. J. (1983). Contribution of adenosine to arteriolar autoregulation in striated muscle. Amer. J. Physiol. 244, H567-H576. RENEMAN, R. S., SLAAF, D. W., LINDBOM, L., TANGELDER, G. J., AND ARFORS,K.-E. (1980). Muscle blood flow disturbances produced by simultaneously elevated venous and total muscle tissue pressure. Microvasc. Res. 20, 307-318. SLAAF, D. W., AND WIEDERHIELM, C. A. (1982). Cessation and onset of muscle capillary flow at reduced arterial pressure. Microvasc. Res. 23, 274. SLAAF, D. W., AND WIEDERHIELM, C. A. (1982). Pressure autoregulation in muscle of unanesthetized bat. Int. J. Microcirc. Clin. Exp. 1, 322. SULLIVAN, S. M., AND JOHNSON,P. C. (1981). Effect of oxygen on blood flow autoregulation in cat sartorius muscle. Amer. J. Physiol. 241, H807-H815. TANGELDER, G. J., SLAAF, D. W., AND RENEMAN, R. S. (1984). Skeletal muscle microcirculation and changes in transmural and perfusion pressure. Prog. Appl. Microcirc. 5, 93-108. WIEDEMAN, M. P., TUMA, R. F., AND MAYROVITZ, H. N. (1981). “An Introduction to Microcirculation.” Academic Press, New York. WIEDERHIELM, C. A., BOUSKELA, E., HEALD, R., AND BLACK, L. (1979). A method for varying arterial and venous pressures in intact, unanesthetized mammals. Microvasc. Res. 18, 124-128. WIEDERHIELM, C. A., AND WESTON, B. V. (1973). Microvascular, lymphatic, and tissue pressures in the unanesthetized mammal. Amer. J. Physiol. 225, 992-996. WIEDERHIELM, C. A., WOODBURY,J. W., KIRK, S. E., AND RUSHMER,R. F. (1964). Pulsatile pressures in the microcirculation of the frog’s mesentery. Amer. J. Physiol. 207, 173-176. WIEDERHIELM, C. A., AND SLAAF, D. W. (1987). A new skeletal muscle preparation for the study of microvascular function in intact, unanesthetized animals. Microvasc. Res., 33, 413-416. Z~EIFACH, B. W. (1974). Quantitative studies of microcirculatory structure and function. I. Analysis of pressure distribution in the terminal vascular bed in cat mesentery. Circ. Res. 34, 843-857.