J. Phy8iol. (1974), 239, pp. 89-102 89With 2 text-figure8Printed in Great Britain

THE CAROTID SINUS BARORECEPTOR REFLEXIN THE PREGNANT RABBIT

BY P. W. HUMPHREYS AND N. JOELSFrom the Department of Physiology, The Medical College of

St Bartholomew's Hospital, Charterhouse Square,London EC1M 6BQ

(Received 19 September 1973)

SUMMARY

1. The reflex responses to baroreceptor stimulation have been comparedin eight pregnant and eight non-pregnant anaesthetized female rabbits.

2. The vascularly isolated, innervated carotid sinus was exposed for30 sec to a series of non-pulsatile pressures ranging from 30 to 230 mmHg.The contralateral sinus nerve and both aortic nerves were cut. Systemicarterial pressure and heart rate were measured at each sinus pressure.

3. The range of arterial pressure change which could be evoked from theisolated innervated sinus was less in the pregnant than in the non-pregnantrabbits. Mean changes were 98 and 61 mmHg respectively. On the otherhand changes in heart rate were similar in the two groups (45 and 43 beats/min respectively).

4. The smaller blood pressure response in the pregnant animals resultedfrom a lesser rise in systemic arterial pressure at low levels of sinuspressure. At high sinus pressures the blood pressure fell to a similar levelin both groups of animals.

5. Pressure on the great vessels by the gravid uterus was not a factorsince there was no consistent difference between the responses obtainedwith the rabbit lying on its back or on its side.

6. Mechanisms which might be responsible for the difference found arediscussed.

INTRODUCTION

The carotid sinus baroreceptor reflex produces widespread and profoundeffects on the cardiovascular system, including changes in heart rate andin the calibre of the resistance vessels in muscle, skin and splanchnic bed(Heymans & Neil, 1958). Pregnant animals are usually avoided whenbaroreceptor reflexes are under study, since occasional experience suggeststhat these animals do not respond 'normally'. This is hardly surprising in

P. W. HUMPHREYS AND N. JOELSview of the considerable circulatory alterations during pregnancy, and ittherefore seemed of interest to examine specifically the baroreceptor reflexin the pregnant animal and compare the responses with those seen in thenon-pregnant female. Rabbits were chosen for this study since animalswith pregnancies of known duration are readily obtainable in this species.

METHODS

Eight New Zealand White rabbits of 24-29 days gestation (pregnancy lasts 31 daysin the rabbit) and a control group of eight non-pregnant female rabbits were used.The mean weight of the pregnant rabbits was 4-09 kg and that of the non-pregnantrabbits was 3-86 kg. The animals were anaesthetized with a 3% solution of pento-barbitone sodium B.P. in 0-9% NaCl, administered through an ear vein. The meandose required to induce anaesthesia was the same, 1-6 mg/kg, in the pregnant andnon-pregnant groups. Supplementary doses of 0-2-0-5 ml. were given as necessaryto maintain a steady plane of anaesthesia which was as nearly identical as could bejudged in all the animals. The plane chosen gave a maximum level of resting bloodpressure. Lightening the anaesthesia would lead to a fall in both blood pressure andairway CO, and the appearance of a- withdrawal response to gentle squeezing betweenthe toes.

Cannulae were inserted into the trachea, a femoral vein and a femoral artery, thearterial cannula being advanced into the abdominal aorta. A saline-dextrose solution(1 part of 0 9% NaCl to 4 parts of 5% dextrose) was infused through the venouscannula at a rate of approximately 1-5 ml./kg. hr. Throughout the dissection andexperiment the inspired air was slightly enriched with 02 by passing a gentle streamof the gas over the tracheal cannula. Body temperature was maintained at 38-39 'C.with the aid of heating lamps when necessary.

Isokation of the carotid 8inus. The right carotid sinus was partially isolated bytying all the arterial branches arising from the region of the bifurcation with theexception of the external and common carotid arteries. Complete vascular occlusioncould then be achieved by placing clips on these vessels. Between tests the clips wereremoved to restore the normal pulsatile blood flow to the sinus region. The contra-lateral sinus nerve was divided and both aortic nerves were cut at their junctionwith the superior laryngeal nerve to minimize compensatory changes due to alteredactivity of baroreceptors in other regions.

After completion of the dissection heparin, 1000 i.u./kg (Pularin, Evans Medical,1000 i.u./ml.), was injected i.v. and a T-cannula inserted in the right common carotidartery. The stem of the T-cannula led to the perfusion apparatus which compriseda small reservoir containing oxygenated saline with an air space above. The reservoircould be placed in communication with the T-cannula by turning a tap. The air spacewas connected to a much larger tank of compressed air and by altering the com-pressed air pressure various non-pulsatile pressures could be applied to the carotidsinus. The pressure within the sinus was measured by a manometer connected througha side tube with the inlet to the rabbit.

Tedt procedure. To examine the reflex effects of subjecting the carotid sinus baro-receptors to different non-pulsatile pressures, the vascular isolation of the sinuswas completed by placing clips on the external carotid artery and on the commoncarotid artery below the T-cannula, and switching in the saline reservoir which hadbeen set to provide the desired pressure. The clips could be positioned and the reser-voir tap turned in less than 2 sec. Pressure within the sinus was maintained steady

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BARORECEPTOR REFLEX IN PREGNANCYfor 30 sec. Prior to each test the polyethylene tube connecting the reservoir withthe T-cannula was filled with blood by allowing some blood to run back into it fromthe carotid artery. This tube had a capacity of about 0-4 ml. and during the courseof a single test less than one-quarter of the blood was displaced by saline. Thus thecarotid sinus must have remained filled with blood throughout.

Recordings. Systemic arterial pressure and carotid sinus pressure were measuredby transducers (Consolidated Electrodynamics, Type 4-327-L221). The signals wereamplified by carrier amplifiers (S.E. Laboratories, Type 432/1) and displayed ona direct-writing U.V. recorder (S.E. Laboratories, Model no. 2100). Mean arterialpressure was obtained by passing the systemic pressure signal through a simpleR-C network with a time constant of 1 sec and was recorded by a separate galvano-meter. The recorder was run at a speed of 5 mm/sec, sufficient to permit heart rateto be counted from the pressure pulses. Tidal C02, measured by an infra-red C02analyser (Hartman & Braun, Type URAS 4) and tidal volume, measured by anintegrating pneumotachograph (Godart NV), were also displayed on channels of theU.V. recorder. These measurements of tidal C02 and tidal volume were used princi-pally, in conjunction with occasional arterial blood gas measurements, to aid themaintenance of a steady state of anaesthesia, but also showed whether or notrespiration was altered during the test procedures.

Blood gases. Arterial blood samples (0-7 ml.) were withdrawn into syringes an-aerobically and their pH, P02 and PCO2 measured immediately at 380 C with aRadiometer Type PHM 27b pH meter and Type PHA 927b Gas Monitor usingRadiometer electrodes.

RESULTS

Each experiment comprised a series of tests in which clips were placedon the common and external carotid arteries of the side of the vascularlyisolated sinus and a steady non-pulsatile pressure applied to the carotidsinus for 30 sec. This was found to be a suitable period for the changes inblood pressure and heart rate to become fully established. A range ofsteady pressures was used which encompassed at its lower end those whichled to maximum rises in blood pressure and heart rate, and at its upperend pressures which evoked maximum falls in these cardiovascularparameters.

Control valuesTable 1 shows the control values for blood pressure, heart rate, arterial

CO2 tension and pH. These values for blood pressure and heart rate arethe means of the values at the beginning of each test, i.e. immediatelybefore applying the arterial clips, when the carotid sinus was exposed tothe animal's pulsatile blood pressure. The arterial blood sample was with-drawn midway through the series of tests. Arterial 02 tension was alwaysin excess of 100 mmHg. The readings have not been included in Table 1as the meter was not calibrated for levels of Po, above 150 mmHg; suchvalues were present in about half of the animals.As can be seen from Table 1 there was a tendency for both PCa2 and pH to

be slightly lower in the pregnant group, but the only significant difference

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P. W. HUMPHREYS AND N. JOELS

between the two groups of rabbits was the level of arterial pressure,which was lower in the pregnant group. These values for our pregnantanimals in Table 1 are almost identical with those reported by Duncan(1969) in pregnant rabbits anaesthetized with sodium pentobarbitone(arterial pressure 82 mmHg; arterial pH 7.36). The rectal temperatureswere also very similar; 38-6 + 0-4 (S.D.) 0 C in the non-pregnant, 38-2 + 0-9(S.D.) °C in the pregnant animals.

TABLE 1. Control values for blood pressure, heart rate, arterial PCO and pH. Onesinus nerve and both aortic nerves cut. The P values indicate the significance ofthe difference between the means of these readings in the non-pregnant and pregnantanimals

CONTROL VALUES

Non-pregnant rabbitsB.P. Heart rate Pa, co2

Expt. no. (mmHg) (beats/min) (mmHg) pH

NPI 105 263 26 7-42NP2 103 270 37 7-37NP3 88 277 37 7-41NP4 119 243 26 7.53NP5 94 281 30 7-39NP6 120 253 29 7-38NP7 123 258 38 7-40NP8 101 276 40 7-37

Mean + S.D. 106-6 ± 12-8 265-1 ± 10-2 32-9 + 5*7 7-41 + 0-05

Pregnant rabbitsB.P. Heart rate Pa.CO2

Expt. no. (mmHg) (beats/niin) (mmHg) pH

Pi 91 223 29 7-44P2 97 248 29 7-29P3 93 294 28 7-35P4 96 252 31 7-31P5 71 274 33 7-31P6 93 264 26 7-43P7 82 276 22 7-34P8 78 285 26 7.39

Mean+ S.D. 87-6 + 95 264-5 ± 22-9 28-9 + 4.7 7-36 + 0-06P <0-01 >0-9 0-2>P>0-1 01>P>0-05

Effect of changes in sinus pressure on arterialblood pressure and heart rate

The levels of arterial pressure and heart rate resulting from the applica-tion to the carotid sinus for 30 sec of a series of non-pulsatile pressuresare shown in Fig. 1. Each series involved at least ten such tests and judged

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BARORECEPTOR REFLEX IN PREGNANCY

from the levelling off at the extremities of the curves in Fig. 1 the pressuresapplied appear to have spanned the full operating range of the carotid-sinus baroreceptors. The curves have the sigmoid shape described in simi-lar studies by other workers on the dog, cat and rabbit (Koch, 1931;Heymans, Bouckaert & Dautrebande, 1931; Schmidt, Kumada & Sagawa,1971; Humphreys & Joels, 1972).

Non-pregnant rabbits

E250 -S 300,,

200Fr NPI] NP2 NP3 NP4 0015 -275100 - 250

50 1j0 225Larotid 2inus pressure (mm)00

200 NP5 NP6 NP7 NP8 3001 L X 275

. 1. R e 250

30 sec ontaaea siu nev nEohsr evsscind

E ~~~~~~~~~~~~~~~~22520

Pregnant rabbits a~~200 ~ P1 P2 N/P3] P 300

*~150 h 275

[in Fig.A275 Inti iueterne ewe ai n iiu

10 250

vaueofbodpesreadhatrt,2banda5owadhg iu

~~~~~ 100 ~ ~~ ~ ~ ~ ~ ~ ~ ~~~0

200 -ptVI P 300sure orP P6 P7 T8 _ 2

100of A 2505s LizJ 225

50 150 250 50 150 250 50 150 250 50 150 250Carotid sinus pressure (mmHg)

Fig. 1. Responses of blood pressure (i) and heart rate (0) to subjectingthe vascularly isolated carotid sinus to various non-pulsatile pressures for30 sec. Contralateral sinus nerve and both aortic nerves sectioned.

The responses of the pregnant and non-pregnant animals are comparedin Fig. 2. In this Figure the ranges between maximum and minimumvalues of blood pressure and heart rate, obtained at low and high sinuspressures respectively, have been plotted against the control blood pres-sure or heart rate for that particular animal. The Figure shows that therange of blood pressure response is diminished in the pregnant animal, andsuggests that in the pregnant rabbit arterial pressure rises to a smallerextent when carotid sinus pressure is reduced, but that when pressurein the isolated sinus is raised arterial pressure falls to similar levels

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P. W. HUMPHREYS AND N. JOELS

irrespective of pregnancy. Fig. 2 also suggests that the range of heart rateresponses is the same in the two groups. These impressions are confirmedin Table 2 where it can be seen that both the range of arterial pressureresponse and the arterial pressure levels reached at low sinus pressure aresignificantly lower in the pregnant group. On the other hand there is nosignificant difference between pregnant and non-pregnant rabbits in thelevels to which arterial pressure is depressed when sinus pressure is raised,or in the range of heart rate response and the maximum and minimumheart rates observed.

1Z 200 - 350 -

E L

150 1300

CL

C. 50L10i 225 250 275 300isControl arterial pressure (mmHg) Control heart rate (beats/min)

Fig. 2. Left hand panel: the maximum and minimum arterial pressure valuesand the range of the arterial pressure responses obtained from the isolatedsinus (ordinate) plotted against the control arterial pressure (abscissa) inthe same experiment. Continuous lines, non-pregnant rabbits; interruptedlines, pregnant rabbits. Right hand panel: as in the left hand panel but showsthe heart rate response.

TABLE 2. Maximum and minimum values and range of responses (± S.D.) of arterialpressure and heart rate when one carotid sinus was subjected to a series of steadypressures. Opposite sinus nerve and both aortic nerves sectioned. Values are averagesof the responses in the eight non-pregnant and eight pregnant rabbits except for theresults marked with the asterisk. These were derived from seven non-pregnant rabbitsonly; the eighth animal developed pulsus alternans at low sinus pressures

Signifi-cance of

Non-pregnant Pregnant differencerabbits rabbits P

Arterial (ressureMaximum 145-0+ 16-6 102-3± 14-3 < 0-001(mmrlgpresure Minimum 47-4 + 12-6 41-5 + 5-3 > 0-2

(mnuurlig) IRange of response 97-6± 27-5 60-8 + 17-4 < 0-01Heart[rateMaximum 276-3 + 13.2* 269-3 + 22-8 > 0-4

(beatsrmin) Minimum 228-9 + 9-6 226-0 + 30-6 > 0-8(Range of response 45-1+ 15.2* 43-3+16-4 > 0-9

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BARORECEPTOR REFLEX IN PREGNANCY

Influence of control blood pressure level on the responsesThe pregnant rabbits as a group had a lower control arterial pressure.

This was not entirely unexpected since a lower resting arterial bloodpressure has been reported in pregnant women (e.g. MacGillivray, Rose &Rowe, 1969). Nevertheless, it raises the possibility that a lower arterialpressure of itself might be responsible for the difference between the reflexbaroreceptor effects in the pregnant and non-pregnant rabbits. However,inspection of Fig. 2 reveals that within each group of rabbits, i.e. pregnantor non-pregnant, there is little suggestion that the range of blood pressureresponse diminishes appreciably when the control arterial pressure islower.

TABLE 3. Comparison of the five non-pregnant rabbits with the lowest, and the fivepregnant rabbits with the highest control arterial pressures. The table shows theminimum and maximum values and range of responses (± S.D.) of arterial pressureand heart rate when one carotid sinus was subjected to a series of steady pressures.Opposite sinus nerve and both aortic nerves cut. Note that the significant differencesbetween the pregnant and non-pregnant groups in Table 2 are also present in theseanimals

Signifi-cance of

Non-pregnant Pregnant differencerabbits rabbits P

Arterial pressure (Maximum 137-2 + 13-5 107-6 + 3.2 < 0-01response -Minimum 438 +14-7 42-2 + 5.1 > 0-8(mmHg) tRange 93-4 + 14.2 65-4 + 7.7 < 0-05

Heart rate (Maximum 281-4+12-1 261-0+25-2 > 0-1response lMinimum 232-0 + 7-8 209-8 + 27-1 > 0-1(mmHg) lRange 49-4+ 15-6 51.2+ 13-1 > 0-8

As a further check we selected the five non-pregnant rabbits with thelowest control arterial pressures and the five pregnant rabbits with thehighest control arterial pressures to obtain two groups with very similarcontrol pressures. The mean arterial pressure was 98 mmHg (range 88-105)in the non-pregnant rabbits and 94 mmHg (range 91-97) in the pregnantanimals. The corresponding heart rates were 273 beats/min (mean, range263-281) and 256 beats/min (mean, range 223-294) respectively.When the effects of altering sinus pressure in these two groups were

compared (Table 3) there were still significant differences in the maximumarterial pressures at low sinus pressure and in the range of arterial pressureresponse.

PH Y 239

95

4

P. W. HUMPHREYS AND N. JOELS

Influence of posture on the reflex baroreceptor responsesAll the foregoing experiments were carried out with the rabbit lying on

its back. Arguably, the weight of the gravid uterus, lying on the posteriorabdominal structures, might have been a factor influencing the barorecep-tor reflex effects in this position. Therefore in several experiments, oncethe curves relating carotid sinus pressure to arterial pressure and heartrate had been determined, a series of tests was performed with the rabbitlying alternately on its back and on its side. In each position the sinuswas subjected to the same low (30-35 mmHg) and high (200-220 mmHg)pressures. The comparison was made in two non-pregnant and fourpregnant rabbits and the maximum and minimum blood pressures observedin each position with the sinus exposed to low and high pressures respec-tively are shown in Table 4. There was no consistent difference betweenthe results in the two positions and the mean differences were negligible.

TABLE 4. Comparison of effects on arterial blood pressure of distending the carotidsinus with a low (30-35 mmHg) and high (200-220 mmHg) pressure with the rabbiton its side and on its back. Values for arterial pressure in mmHg. Numbers inbrackets indicate number of tests of each procedure. The value given is the meanfor these tests

Maximum arterial pressure Minimum arterial pressure(Low sinus pressure) (High sinus pressure)

, x 5 ~~~~~rADiffer- Differ-ence enceside- side-

Experiment Side Back back Side Back back

NP7 Non- regantf 151 (5) 154 (5) -3 66 (2) 66 (2) +3NP8J prgn1 108 (4) 121 (4) -13 49 (2) 52 (2) -3P4 105 (4) 104 (5) + 1 43 (2) 45 (2) -2P5 70 (1) 74 (1) -4 39 (1) 45 (1) -6P6 regnan 125 (4) 120 (4) +5 77 (2) 55 (2) +422P7 74 (4) 76 (4) -2 41 (4) 39 (4) +2

Mean -2-7 Mean +2 7

DISCUSSION

These experiments show that the reflex response to carotid sinus baro-receptor stimulation in the pregnant rabbit differs from that in the non-pregnant animal, in that the range of systemic arterial pressure variationwhich can be provoked by alterations in sinus pressure is much less in thepregnant state. Conversely, there was no difference between the heartrate changes induced in the two groups of rabbits.

Before discussing these findings in detail, three factors which might

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BARORECEPTOR REFLEX IN PREGNANCY 9

have influenced the results will be considered: whether the level of anaes-thesia was comparable in the pregnant and non-pregnant rabbits; whetherchemoreceptor stimulation at the lower sinus pressures could have con-tributed to the effects; and the likelihood of mechanical obstruction toblood flow by the gravid uterus.

Despite the lower control blood pressure in the pregnant animals therewas no reason to suppose that the level of anaesthesia was any deeper.Pregnant women also have a lower blood pressure than non-pregnantwomen (e.g. Walters, MacGregor & Hills, 1966; MacGillivray et al. 1969).However, the difference was likely to have been accentuated in our animalssince the aortic nerves and one sinus nerve had been cut, and as the resultshave indicated, the pressor response to the removal of baroreceptorrestraint was diminished in the pregnant rabbit. As described in Methods,considerable care was taken in these experiments to maintain a similardepth of anaesthesia in all the rabbits. Control values of heart rate, rectaltemperature and blood pH were almost identical in the pregnant and non-pregnant groups; moreover, there was virtually no difference between thetwo groups in the reflex changes in heart rate. Arterial P002 tended to bea little lower in the pregnant rabbits. A low alveolar Pc02 is a normal find-ing in human pregnancy (Boutourline-Young & Boutourline-Young, 1956).The likelihood of chemoreceptor stimulation at the lowest sinus pressures

used must be considered since severe stagnant hypoxia is a proven stimu-lant of the carotid body chemoreceptors (Landgren & Neil, 1951; Biscoe,Bradiey & Purves, 1970). To minimize this possibility sufficient oxygenwas added to the inspired air to maintain full saturation of the arterialblood, and the arterial Po, was always in excess of 100 mmHg. The absenceof any consistent difference between the responses of systemic arterialpressure and heart rate at carotid sinus pressures of 50 and 30 mmHgargues against chemoreceptor stimulation by stagnant hypoxia. Nor wasthere any increase in pulmonary ventilation during the 30 sec test periodat low sinus pressure.Although the rabbits were lying supine, it is unlikely that the gravid

uterus would have occluded the inferior vena cava in the rabbit as it doesin women (Scott & Kerr, 1963; Lees, Scott, Kerr & Taylor, 1967), sincein the rabbit the uterus is bicornuate and in the supine position the weightof the fetuses does not press directly on the great vessels. Nevertheless, incase some obstruction might have impaired the reflex response to reducedsinus pressure, the responses of several animals were tested when theywere lying both on their side and supine. In every case the responses werethe same in either position.The most obvious effect of pregnancy on the baroreceptor reflex was to

reduce the range of blood pressure change which could be evoked by altering4-2

97

98 ~P.W. HUMPHREYS AND N. JOELS

the pressure within the carotid sinus. This might result from a reductionin baroreceptor sensitivity or a modification of the effector side of theresponse. A reduction in baroreceptor sensitivity seems improbable sincethe range of heart rate responses produced by the baroreceptors was un-affected by pregnancy, and since high sinus pressures reduced systemicpressure to similar low levels in both groups. The explanation for the poorpressor response to reduced sinus pressure thus appears most probably toreside in the effector mechanisms, the heart and the peripheral vasculature.

The heart. Several authors (Leusen, Demeester & De Witte, 1954; Daly &Luck, 1958) have produced evidence for a rise in cardiac output whensinus pressure is reduced, but others (Polosa & Rossi, 1961 ; Groom, Ldfving,Rowlands & Thomas, 1962; Corcondilas, Donald & Shepherd,' 1964) havedenied that this occurs. However, the recent work of Schmidt et al. (1971)clearly establishes that alterations in carotid sinus pressure can causeappreciable inverse changes in cardiac output in the dog. Nevertheless, thelack of a similar study in the rabbit and the paucity of information aboutthe effects of pregnancy on the responses of the heart make it impossibleto assess whether a change in this component of the baroreceptor reflexresponse contributed to the difference between pregnant and non-pregnantrabbits seen in our experiments.

The peripheral vaseulature. The poor hypertensive response of thepregnant animals to a reduction of pressure in the isolated sinus couldbe due equally well to a diminished ability to raise the total peripheralresistance. This. could be ascribed either to a reduced response of theperipheral vessels to their vasoconstrictor innervation during pregnancy,or to the presence of a large vascular bed in the pregnant animal which isnot under vasomotor control from the baroreceptors.

Alteration in vasomotor responsiveness. A large rise in blood flow and fallin vascular resistance occurs in the hands and feet of women duringpregnancy (Ginsburg & Duncan, 1967); indeed, Raynaud (1862) himselfdescribed how a patient of his enjoyed amelioration of her vasospasmwhen she was pregnant. A smaller rise of flow occurs in the kidney (Chesley,1960). There are many reports of the effects of oestrogens and progesteroneupon vasomotor responsiveness. For example, a vasodilator action ofoestrogen in rabbits was described by Reynolds & Foster (1939); Goodrich& Wood (1964) report an increase in forearm blood flow in women takingoral contraceptives; and Lloyd (1959) describes an inhibitory action ofprogesterone on vascular smooth muscle. The vasodilator action of oestro-gens has been ascribed by Haigh, Lloyd & Pickford (19615) both to anincrease in the tissue content of an acetylcholine-like substance and tointerference with the manufacture of adrenaline in, or its release from,sympathetic nerves. Nevertheless, despite this ample evidence for effects

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BARORECEPTOR REFLEX IN PREGNANCY

of female sex hormones on the peripheral vasculature, the extent to whichthey contributed to the reduced blood pressure responses in our experi-ments remains uncertain in the absence of knowledge regarding the cardiacoutput.

Furthermore, constriction of resistance vessels may be only one factorin the vascular response to a fall in sinus pressure. Heymans & Neil (1958)have stressed the contribution of venoconstriction to any rise in cardiacoutput. Though the degree of limb vein constriction when sinus pressure isreduced may be small (Browse, Donald & Shepherd, 1966; Bevegard &Shepherd, 1966; Brender & Webb-Peploe, 1969), venoconstriction in thesplanchnic bed seems well-established (Alexander, 1954; Oberg, 1964;Brender & Webb-Peploe, 1969). Reports of structural alterations in therabbit vasculature induced experimentally by steroids or as a result ofpregnancy (Danforth, Manalo-Estrella & Buckingham, 1964), of increasedvenous distensibility produced in women by pregnancy or oestradiol(Goodrich & Wood, 1964, 1966), and of inhibition by oestradiol and pro-gesterone of the response to electrical stimulation of strips ofhuman venoussmooth muscle (Barwin & McCalden, 1972), may indicate therefore thatimpaired venous contractility could contribute to the smaller responseswhich we have observed in the pregnant rabbits.On the other hand, during pregnancy there is an increase in the volume

of plasma (Hytten & Paintin, 1963), and of red cells (Rovinsky & Jaffin,1965). There does not seem to be any information about the proportionof this increase in the blood volume which is accommodated in the veins,but if a large additional quantity of blood is present in the veins duringpregnancy this might result in the veins operating over a different rangeof their pressure-volume characteristic. Thus venomotor responses could bealtered irrespective of any hormonal effects on the muscle of the vein wall.The uterine vascular bed. The uterine vascular bed increases consider-

ably during pregnancy and if this development were accompanied bya decreased vasomotor responsiveness or the presence of plentiful arterio-venous shunts, then modification of general vascular responses could beexpected.Duncan & Lewis (1969) studied the vasculature of the pregnant rabbit

uterus by means of isotope-labelled microspheres, and concluded that anylarge arteriovenous channels could be only few in number despite the factthat the placenta is classified as haemoendothelial in this species. A some-what unresponsive vascular bed seems more probable. Rosengren &Sjoberg (1968) have described a large depletion of adrenergic transmitterfrom the uterus and its blood vessels in the pregnant rabbit; and a numberof workers who have measured flow in one uterine artery of the pregnantsheep report that, in the resting state, uterine vascular resistance is not

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P. W. HUMPHREYS AND N. JOELS

altered by either spinal anaesthesia (Huckabee, 1962; Ladner, Brinkman,Weston & Assali, 1970) or phenoxybenzamine (Greiss & Gobble, 1967).Ladner et al. (1970) also reported that uterine vascular resistance remainedunchanged when arterial pressure was raised by carotid occlusion, thoughthere was a rise in vascular resistance in the non-pregnant animal.

Burwell (1954) has compared the circulatory effects of the uterinecirculation to those ofan arterio-venous shunt. Such a shunt, or a relativelyunresponsive uterine vascular bed, would be consistent with the diminishedresponse to a reduction in carotid sinus pressure. However, the totaluterine blood flow in rabbits at a comparable stage of pregnancy (27-29 ml./min, Barcroft, Herkel & Hill, 1933; 31 ml./min, Duncan, 1969) onlyamounts to 7% of cardiac output (Duncan, 1969). Thus even though thefraction of the cardiac output delivered to the uterus will rise if vaso-constriction takes place elsewhere, such a shunt mechanism seems unlikelyof itself to account completely for our results.

Our thanks are due to Miss Maureen Best for her valuable technical assistance.We are also grateful to the Medical Research Council and to the St Bartholomew'sHospital Endowment Fund for their generous support.

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BARCROFT, J., HERKEL, W. & HILL, S. (1933). The rate of blood flow and gaseousmetabolism of the uterus during pregnancy. J. Physiol. 77, 194-206.

BARWIN, B. N. & MCCALDEN, T. A. (1972). The inhibitory action of oestradiol-17.fland progesterone on human venous smooth muscle. J. Physiol. 227, 41-42 P.

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BROWSE, N. L., DONALD, D. E. & SHEPHERD, J. T. (1966). Role of the veins in thecarotid sinus reflex. Am. J. Physiol. 210, 1424-1434.

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CHEsLEY, L. C. (1960). Renal functional changes in normal pregnancy. Clin. Obstet.Gynec. 3, 349-363.

CORCONDILAS, A., DONALD, E. D. & SHEPHERD, J. T. (1964). Assessment by twoindependent methods of the role of cardiac output in the pressor response tocarotid occlusion. J. Physiol. 170, 250-262.

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DALY, M. DE B. & LUCK, C. P. (1958). The effects of carotid sinus baroreceptorreflexes on pulmonary arterial pressure and pulmonary blood flow in the dog.J. Physiol. 143, 343-368.

DANFORTH, D. N., MANALO-ESTRELLA, P. & BUCKiNGHAM, J. C. (1964). The effectof pregnancy and of Enovid on the rabbit vasculature. Am. J. Obstet. Gynec.88, 952-962.

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GOODRICH, S. M. & WOOD, J. E. (1964). Peripheral venous distensibility and velocityof venous blood flow during pregnancy or during oral contraceptive therapy.Am. J. Obstet. Gynec. 90, 740-744.

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