Experimental Physiology (1996), 81, 385-396

Printed in Great Britain

THE EFFECT OF DISTENSION OF THE STOMACH ON

PERIPHERAL BLOOD FLOW IN ANAESTHETIZED PIGS
G. VACCA, D. A. S. G. MARY, A. BATTAGLIA, E. GROSSINI
AND C. MOLINARI
Laboratorio di Fisiologia, Dipartimento di Scienze Mediche, Facolta di Medicina e Chirurgia di Novara,
Universita di Torino, via Solaroli 17, 1-28100 Novara, Italy
(MANUSCRIPT RECEIVED 8 NOVEMBER 1995, ACCEPTED 29 JANUARY 1996)

SUMMARY
The present study was undertaken in anaesthetized pigs to determine the primary reflex effects of
gastric distension on the peripheral circulation. Changes in blood flow in the splenic, superior
mesenteric, left renal and left external iliac arteries were assessed using electromagnetic
flowmeters during distension of a balloon in the stomach, performed at constant aortic blood
pressure and heart rate, with 06 1 of Ringer solution (mean gastric transmural pressure of about
12 mmHg). In fourteen pigs, a decrease in splenic, renal and iliac flows and variable changes in
mesenteric flow were obtained. A decrease in mesenteric flow and more marked decreases in the
other flows occurred in response to the distension after the administration of propranolol or
butoxamine. In five pigs, the vasoconstrictive responses were graded by step increments in gastric
distending volume from 0.4 to 08 1. The above responses were abolished by the administration of
phentolamine (eight pigs) and by bilateral cervical vagotomy (six pigs). The results showed that
innocuous distension of the stomach in anaesthetized pigs reflexly caused vasoconstriction in the
splenic, renal and iliac vascular beds; vasoconstriction also occurred in the mesenteric vascular bed
but only after /3-blockade. These reflex responses were mediated by sympathetic mechanisms
which involved both a and ,3 vascular adrenoceptors and their afferent limb was in the vagal nerves.

INTRODUCTION
The stomach contains mechanoreceptors which discharge into afferent vagal and splanchnic
nerve fibres (Janig & Morrison, 1986; Grundy & Scratcherd, 1989). Stimulation of such
receptors in anaesthetized animals has been reported to elicit reflex responses involving the
cardiovascular system, which include variable changes in heart rate and arterial blood pressure
and small increases in left ventricular contractility (Grundy & Davison, 1981; Longhurst,
Spilker & Ordway, 1981; Longhurst & Ibarra, 1982; Kidd, Li & McWilliam, 1984). More
recently, innocuous distension of the stomach in anaesthetized pigs was shown to elicit reflex
increases in heart rate and arterial blood pressure and coronary vasoconstriction without
primarily causing significant changes in left ventricular inotropic state (Vacca & Vono, 1993;
Vacca, Mary & Vono, 1994b). The afferent limb of these reflex responses was in the vagal
nerves and the efferent limb involved sympathetic pathways.
These findings reflect aspects of the heterogeneous nature of sympathetic neural responses
to distension of the stomach. However, reports of the effects of distension of the stomach on
other regional vascular beds in anaesthetized animals have been scarce and could not be
attributed solely to the distension. For instance, gastric distension in anaesthetized cats has
been,reported to cause insignificant changes in several peripheral blood flows, as assessed by
the radioactive microsphere technique (Longhurst & Ibarra, 1984). In this study, the

1434
386 G. VACCA AND OTHERS

concomitant reflex increase in arterial blood pressure was not prevented and could have
masked the primary effects of distension on the measured blood flows through local auto-
regulation or baroreceptor reflex control.
The present study was planned to investigate in anaesthetized pigs the effect of distension of
the stomach on regions of the peripheral circulation and the efferent reflex mechanisms
involved. The blood flow responses in the splenic, intestinal, renal and musculocutaneous areas
to gastric distension were measured whilst preventing the reflex increases in heart rate and
arterial blood pressure.
METHODS

Experiments were performed on fourteen pigs weighing 62-75 kg and supplied by an accredited dealer
(Azienda Cornelia srl, San Pietro Mosezzo, Novara, Italy). The animals were fasted overnight and then
anaesthetized by the admninistration of ketamine (20 mg kg--' i.M.; Parke-Davis, Milan, Italy), which was
followed after about 15 min by sodium pentobarbitone (15 mg kg-' i.v.; Siegfried, Zofingen, Switzerland).
The animals were artificially ventilated with oxygen-enriched air using a respiratory pump (Harvard 613,
Harvard Apparatus, South Natick, MA, USA). Anaesthesia was maintained throughout the experimTents
by a continuous i.v. infusion of sodium pentobarbitone (7 mg kg' h-). 1
Blood pressures in the ascending aorta and the right atrium were recorded via catheters connected to
pressure transducers (Statham P23 XL, Gould, Valley View, OH, USA) inserted into the right fiemoral
artery and the right external jugular vein, respectively. Arterial blood samples were used to measure the
pH, arterial 02 pressure (Pao,) and arterial CO2 pressure (Pa Co) using a gas analyser (IL 1304,
Instrumentation Laboratory, Lexington, MA, USA) and the haematocrit. The acid-base status of the
animals was kept within normal limits as previously reported (Linden & Mary, 1983).
The abdomen was opened through a mid-line incision and the splenic, superior mesenteric, left renal
and left external iliac arteries were dissected free of surrounding tissues. An electromagnetic flow probe
was placed near the origin of each artery, with a plastic snare distal to the flow probe for assessment of
zero blood flow. The flow probes were connected to two sine-wave electromagnetic flowmcters (Model
BLI 613, Biotronex Laboratory Inc., Chester, MD, USA) to make simultaneous measurements in all these
arteries.
The stomach was emptied and a balloon catheter, introduced through a purse-string sutur-e in the fundus
and pushed down to position its tip in the pyloric antrium, was used to perforiii gastric distensions. The
exposed pa.rt of the cannula comprised two sections for the injection of wairmn Ringer solution and the
measurement of the pressure in the balloon. The solution was kept in a reser voir maintained att 38 °C and
wals driven into the intragastric balloon by compressed air. To obtain the gastric transmnural pressure, in
each animal the balloon was distended with the same volumes of Ringer solution planned for the
experiments before insertion into the stomnach and the intraballoon pressure measured. Gastric transmnural
pressure during the experiments of distension was calculated as the differencc betweeni the v\alues of
pressure measured in the intragastric balloon and the values of intraballoon pressure previously obtained.
Preliminary tests of graded distension in steps of 0.2 1 to reach the volume of' 1 2 1 resulted in a gr-aded
increase in gastric transmural pressure which occurred between 0 4 and 1 2 1 and was lineairly related to
the values of distending volume (correlation coefficient (,) = 0.99, P < 0.0005).
To prevent changes in arterial blood pressure during the experiments, the chest was opened in the left
fourth intercostal spaceCaInd a large-bore cannula was introduced into the left internal mammarna-y artery
aind connected to a reservoir primed with Ringer solution and kept ait 38 'C. The reservoir was
pressurized using compressed air, which was controlled with a Starling resistaince, a.nd pressure within the
reservoir was meaisured by a. mercury manometer. This method hals beenl previously shown in
ainaiesthetized dogs and pigs to allow the aortic blood pressure to be mtaintained at steady levels without
significant changes in left ventricular pressures or the haicmnatocrit (Cevese, Drinkhill. Mary. Pa,tel,
Schena & Vacca, 1991; Vatcca & Vono, 1993; Vaccai, Battaglia, Grossini & Papillo, 1994a; Vacca et al.
1 994b). Coagulation of the blood was prevented by i.v. injection of hepar11i1n (Pa1rke-Dalvis, initiail dose
500 i.u. kg 1, subsequent doses of 50 i.u. kg Ievery 30 mm).
 STOMACH DISTENSION AND PERIPHERAL FLOW 387
To pace the heart, electrodes were sewn onto the left atrium and connected to a stimultator (Model
S8800, Grass Instruments, Quincy, MA, USA), which delivered pulses of' 3- 5 V with 2 ms duration at
the required frequency. In six animals the cervical vagal nerves were exposed. The rectal temperature of'
the pigs was monitored and kept between 38 and 40 'C.
Mean aortic and righlt atrial blood pressures, pressure in the intraigastric balloon, mean and phasic
splenic, mesenteric, renal and iliac blood flows were monitored and recorded together with heart rate
using an electrostatic strip-chairt recorder (Gould ES 2000, Gould). The heart ralte was obtained from the
electrocardiogr.lIn.
At the cnd of the experiments, each animal was killed by an intravenous injection of 90 mg kg
sodium pcntob.Lrbitone.
Experiimental protocol
The experiments were performed af'ter a steady state had been attained for at least 30 min with respect
to heart rate, mean aortic blood pressure and mean splenic, mesenteric, renal and iliac blood flows.
Gastric distension was applied in each pig while chacnges in heart rate and arterial blood pressure were
prevented by injecting 06 1 of' Ringer solution into the intragastric balloon. The heatrt rate waIs kept
constant by atrial pacing to a frequency fatster than that observed during a preliminary distension performed
in each animal when cardiovascular parameters were not being controlled. The distensions lasted for a
period of' I min. After the release of the distension, observations continued for a further 2 min. The test
period was during the last 15 s of distension, when a steady state in all measured variables had been
attained. The response to each distension was calculated as the difference between the means of' variables
during the test period and their corresponding control values calculated as the average of' the means from
two 15 s steady-state control periods, one taken immediately before the distension and the other 2 min
after its release. Any change in measured haemodynamic variables was considered as a response only
when it was reversed by the release of the distension. Zero blood flows were checked before and after each
experiment.
To examine the reflex mechanisms involved in the responses of' splenic, mesenteric, renal and iliac
blood flows to gastric distension, the experiments at constant arterial blood pressure were repeated in
eight pigs when a steady staite was attained after blockade of fl-adrenoceptors with propracnolol
(0 5 mg kg-' I.v.; Sigma, Milan, Italy) and in six pigs after blockade of' 2-aadrenoceptors with
butoxamine (2 5 mg kg-' I.v.; Sigma, Milan, Italy). In the eight pigs that received propranolol the
experiments were repeated again after a-blockade with phentolamine (1 mg kg-' i.v.; Ciba-Geigy,
Varese, Italy) and in the six pigs that received butoxamine they were repeated after bilateral section of' the
cervical vagal nerves.
The tests of' distension were carried out at least 10 min after the injection of a- and ,-blocking agents.
The dose of propranolol has been shown in anaesthetized dogs to prevent changes in left ventricular
inotropic state (Harry, Kappagoda, Linden & Snow, 1973) and to abolish the reflex increases in heart rate
and left ventricular (dP/dt)ii1ax (maximum rate of rise of systolic left ventricular pressure) caused by
descending colon distension (Cevese, Mary, Poltronieri, Schena & Vacca, 1992). The same dose has been
shown in anaesthetized pigs to prevent the reflex increase in heart rate caused by gall bladder distension
(Vacca et al. 1994a). A dose of' 2 5 mg kg-1 of' butoxamine was used to block fl2-adrenoceptors in
anaesthetized rats (Waxman, Asta & Cameron, 1994). The same dose in anaesthetized pigs was shown to
prevent the increase in arterial blood pressure elicited by the intravenous injection of growth hormone
(G. Vacca & D. S. A. G. Mary, unpublished observations). The dose of 1 mg kg-l of phentolamine was
shown to abolish the reflex increases in aortic blood pressure caused by descending colon distension in
anaesthetized dogs (Cevese et al. 1992) and by gall bladder distension in anaesthetized pigs (Vacca et al.
1994a). During the experiments performed after the administration of butoxamine the heart rate was
kept constant, pacing the heart at the same frequency as in the previous experiments.
Statistical methods
Student's paired t test was used to examine changes in measured variables during the experiments of'
distension. Analysis of variance and Student-Newman-Keuls test were used to examine the effect of
successive procedures on peripheral blood flows. Group data are presented as means + S.D. (range).
388 G. VACCA AND OTHERS

400- 1500-
I If A

0
_
._

S 300- E 1 200- *

m
-' 200- G 900-
V:
v1

100 600
O 200 300 460 600 900 1200 1500
Control SBF (ml min-') Control MBF (ml min-')
250-
600- 200-
500X 5E 0

150-
400
100-
300- E
200 50 /
200 300 400 500 600 7( 50 100 150 200 250
Control RBF (ml min-1) Control IBF (ml min-')

Fig. 1. The response of mean splenic blood flow (SBF), mean mesenteric blood flow (MBF), mean renal blood flow (RBF)
and mean iliac blood flow (IBF) to stomach distension in the 14 pigs. The values obtained during the test period of
distension are plotted on the ordinate against the control values on the abscissa. The continuous line is the line of equality.

RESULTS
In the fourteen pigs, recordings commenced approximately 5 h after the induction of
anaesthesia. The mean values of parameters measured were: pH, 7 40 + 0-03 (7-36-7-44);
Pa,02 (mmHg), 120 + 11 (98-151); Pa,C02 (mmHg), 39 + 1.4 (38-43); and haematocrit (%),
36 + 1 7 (32-39). During preliminary experiments of gastric distension an increase in mean
aortic blood pressure (mmHg) of 10 + 3 (6-16) (P < 0.0005) from a control value of
106 + 20*8 (78-140) and a small increase in heart rate (beats min-') of 3 + 1-2 (1.1-4-9)
(P < 0.0005) from a control value of 135 + 28.4 (102-176) were obtained. These changes
indicated that the animals used for the present investigation were responsive to distension of
the stomach and allowed the determination of responses in heart rate for the subsequent use in
atrial pacing.

Responses of the regional blood flows

Mean aortic blood pressure was held constant during the control and test periods at (mmHg)
107 + 19-6 (80-141) and 106 + 20*9 (78-140), respectively. Paced heart rate (beats min-)
was 160 + 21 (120- 190) during control periods and 160 + 20 (120- 190) during test periods
while mean right atrial pressure (mmHg) was 2.4 + 1-2 (0-2-5) during control periods and
2-4 + 1-2 (0-3-4.7) during test periods. During the distension mean gastric transmural
pressure (mmHg) was 11-6 + 3.5 (7-19).
Control values of abdominal and iliac blood flows were (ml min-'): splenic, 284 + 78
(164-393); mesenteric, 979 208 (697-1265); renal, 422 + 138 (229-677); and iliac,
 STOMACH DISTENSION AND PERIPHERAL FLOW 389

A B C
HR 180r
(beats min-') 140L

ABP 1i10
(mmHg) lo:
RAP 5
(mmHg) 0

Mean SBF 350

(mlmm ) 200 L

Phasic SBF 400[ AMI J, W AMAM.

(ml min-1) 200[
Mean MBF 1250 r
(mlmin ) 800 L
Phasic MBF 1600 F ) A J4
(ml min ) 800 L

Mean RBF 550 r

(ml min-') 400 L

(ml min-) 350 L }

BP 30 E -_-
(mmHg) 0
Mean IBF 150
(ml min') _1 l_
250
Phasic IBF
(ml min-') L
AIillIIIIIi
Ss

Fig. 2. Example of experimental recordings taken before (A), during (B) and after (C) distension of the stomach in an
anaesthetized pig. From the top are shown heart rate (HR), mean aortic blood pressure (ABP), mean right atrial pressure
(RAP), mean and phasic splenic blood flow (SBF), mean and phasic mesenteric blood flow (MBF), mean and phasic
renal blood flow (RBF), pressure in the intragastric balloon (BP), mean and phasic iliac blood flow (IBF).

131 + 42 (83-217). Individual changes in blood flow as a result of gastric distension are
shown in Fig. 1. Group changes are shown in Table 1. Gastric distension caused decreases in
splenic, renal and iliac blood flows, which occurred in each of the fourteen pigs. These
decreases, as percentages of control values, amounted to 9-3 ± 5*8 (2.8-22) (P < 0-0005),
6*3 + 3.5 (1.8-13-2) (P < 0-0005) and 8.3 + 5 (1.8-19-2) (P < 0.0005), respectively. Changes
in mesenteric blood flow were variable and insignificant: mesenteric blood flow increased in
six pigs, decreased in six pigs and did not show any change in two pigs (Fig. 1). These
changes, expressed as a percentage of control values, amounted to 1-0 + 5.3 (-6.8 to 13-4)
390 G. VACCA AND OTHERS

400- 1300 -

E 300- /E /0
UL.
L 200 / : 700

1(0 400
100 200 300 400 400 700 1000 1300
Control SBF (ml min-') Control MBF (ml min-')
600- 250-
500 20
E
1400 .-1 50
X`02)(
LL.~~~~~~~~~~~U
300 g
200 -10
100 50
100 200 300 400 500 600 50 100 150 200 250
Control RBF (ml min-') Control IBF (ml min-')

Fig. 3. The response of mean splenic blood flow (SBF), mean mesenteric blood flow (MBF), mean renal blood flow (RBF)
and mean iliac blood flow (IBF) to stomach distension in the 14 pigs after the administration of propranolol or
butoxamine.

(P > 0.20). An example of experimental recordings taken in one pig is shown in Fig. 2. In this
experiment mean splenic, renal and iliac blood flows decreased by 44, 31 and 13 ml min-',
respectively, from averaged control values of 300, 509 and 125 ml min-', while mean
mesenteric blood flow increased by 102 ml min-' from an averaged control value of
1019 ml min-'.
Experiments with propranolol or butoxamine
In eight pigs, the administration of propranolol caused a decrease in heart rate (beats min-')
of 38 + 23-3 (6-70) (P < 0.0025) and an increase in mean aortic blood pressure (mmHg) of
15-4 + 7.9 (5-26) (P < 0.0005). In six pigs, the administration of butoxamine caused an
increase in mean aortic blood pressure (mmHg) of 10 + 5 6 (6-20) (P < 0.005), which was
accompanied by a decrease in heart rate (beats min-') of 9.1 + 2 9 (6-14) (P < 0.0005).
These changes elicited by the administration of the chemical agents were accompanied in the
fourteen pigs by group decreases in mean blood flows (ml min-') as follows: splenic,
23 + 40 (-113 to 45) (P <0.05); mesenteric, 67 + 100 (-215 to 200, P <0.025); renal,
55 + 72 (-190 to 46) (P < 0.01); and iliac, 16 + 18 (-71 to 4) (P < 0.05). During the
experiments performed after the administration of the blocking agents, gastric transmural
pressure (mmHg) was 11 + 3 1 (8-17).
Individual responses in blood flows during the experiments are given in Fig. 3. Group
changes are shown in Table 1. After the administration of propranolol or butoxamine
distension of the stomach caused in each pig a decrease in all measured regional blood flows.
Changes in the other haemodynamic variables were insignificant (at least P > 0.05). The
group decreases in mean abdominal and iliac blood flows, as percentages of control values,
 STOMACH DISTENSION AND PERIPHERAL FLOW 391

A B C
HR 12O0
(beats min-') 80L
ABP 125 E
(mmHg) 105E
RAP 5E
(mmHg) 0

30
Mean SBF
(ml min-') 200L

Phasic SBF 350 [ fA A AA RA

(ml min') 150L WWWWW4WNW~4~

Mean MBF 1000_ r _ _

(ml min ) 700L
Phasic MBF 1400[ , !AA A AA A
(ml min-1) 600

Mean RBF 500 -------

(ml min ) 350 L

750 r
Phasic RBF [ # M
(ml mnin-') 300L
BP 30 E
(mmHg) 0 ---

Mean lBF 150

(ml min ') goE
25Or-
Phasic IBF[
(rnl mill-1)
5s

Fig. 4. Example of experilnental recordings taken belore (A), during (B) an1d aifter (C) distension of' the stomcach after the
administraition of propranolol in the same animal as in Fig. 2. The layout is as in Fig. 2.

were as follows: splenic, 16 4 + 8 5 (5.5-33 2) (P < 0.0005); mesenteric, 11 8 + 5 8 (4 7-22.7)

(P <00005); renal, 11.8 + 72 (4 8-32 5) (P <0.0005); and iliac, 15 + 59 (4.6-24.6)
(P < 0.0005). An example of these responses in the animal of Fig. 2 is shown in Fig. 4. In this
experiment mean splenic, mesenteric, renal and iliac blood flows decreased by 50, 139, 72 and
16 ml min-1 from averaged control values of 280, 919, 449 and 115 ml min-', respectively.
The responses of splenic, renal and iliac vasoconstriction were enhanced with respect to the
responses obtained before the administration of the chemical agents in twelve, fourteen and
twelve pigs, respectively. Considering all the animals, despite the group decreases in the
baseline values of peripheral flows caused by ,-blockade, the responses to gastric distension
were significantly greater than those obtained before giving the blocking agents (at least
P <0.0025).
392 G. VACCA AND OTHERS

Table 1. Changes in peripheral blood flow (ml min-m) caused by gastric distension
SBF MBF RBF IBF

Control -26 + 21* 20 + 62 -26 + 15* -11 +8*

(-73 to -9) (-48 to 169) (-57 to -9) (-34 to -3)
After propranolol -44 ± 31 * -107 + 64* -44 + 31 * -16 + 7 *
or butoxamine (-121 to -15) (-248 to -43) (-126 to -11) (-31 to -8)
After phentolamine -1 + 5 4 + 21 -2 + 6 1+ 3
(-8 to 5) (-20 to 52) (- 12 to 7) (-2 to 5)
After bilateral -1 ± 5 3+6 -1 + 3 -0.3 + 2
vagotomy (-10 to 2) (-5 to 10) (-5 to 3) (-4 to 2)

Data are means + S.D. (range) for n = 14 or n = 8 (after propranolol or butoxamine) and n = 6 (after bilateral vagotomy).
SBF, mean splenic blood flow; MBF, mean mesenteric blood flow; RBF, mean renal blood flow; IBF, mean iliac blood
flow. * Significant difference from control values, P < 0.0005.

Responses to graded distension. In five pigs, the stomach was distended in three successive
steps to volumes of 0.4, 0-6 and 0-8 1. The corresponding values of transmural pressure
(mmHg) were: 8-6 + 4 2 (4-15), 11.8 + 3.9 (9-17) and 14*8 + 5.3 (11-23). In each pig, the
increase in the distending volume augmented the response of decreases in measured flows.
Group decreases in blood flow (ml min-') for the three levels of distension were, respectively,
splenic: 20 + 20 (7-56) (P < 0.05), 59 + 23 (42-99) (P < 0.0025) and 82 + 25 (67-127)
(P < 0-0025); mesenteric: 93 + 81 (20-198) (P < 0.05), 135 + 99 (43-248) (P < 0.025) and
153 + 96 (64-260) (P < 0-0125); renal: 39 + 33 (7-92) (P < 0.05), 64 + 41 (14-126)
(P < 0.025) and 90 + 52 (23-167) (P < 0.01); iliac: 7 + 5 (3-16) (P < 0.025), 16 + 9 (10-31)
(P < 0.01) and 22 + 8 (14-36) (P < 0.0025). The decreases in splenic, mesenteric, renal and
iliac blood flows obtained with the distending volume of 0.8 1 were significantly greater
(P < 0.0025, P < 0.01, P <2,025 and P < 0 01, respectively) than the decreases obtained with
the distending volume of 0 6 1, which in turn were significantly greater (P < 0-0005, P < 0.01,
P < 0-005 and P < 0 01, respectively) than the decreases caused by the distending volume of
0-4 1. Individual percentage decreases in the blood flows with respect to the control values are
illustrated in Fig. 5.

Experiments with phentolamine

The administration of phentolamine caused in the eight pigs a decrease in mean aortic blood
pressure (mmHg) of 29 + 15.2 (11-56) (P < 0.0025). This decrease was accompanied by an
increase in heart rate (beats min-') of 11 + 5 6 (3-21) (P < 0.0005), by small group decreases
in splenic, mesenteric and renal blood flows, which respectively amounted to (ml min-)
47 + 58 (-153 to 10) (P <0.05), 23 + 104 (-153 to 104) (P >0.25) and 10 + 44 (-50 to 72)
(P > 0.25), and by a small group increase in iliac blood flow of 10 ± 15 (-13 to 30)
(P > 0.05). During the experiments performed after the administration of the drug, gastric
transmural pressure (mmHg) was 10.6 + 3 1 (7-17).
Group changes in blood flow during the experiments of distension are given in Table 1. The
administration of phentolamine completely abolished in each pig the responses of the regional
blood flows previously elicited in the same animals by gastric distension. Changes in the other
haemodynamic variables during the experiments were insignificant (at least P > 0.20).
 STIOMIACHI DISTENSION A\NL) 1't'RIPIIERLAI FLO()\' 393

SBF 1 BI

41)

RBF IBI

- >() _

2 3 4 51 2 3 4 5

Fig. 5. The Img1itudeIC ol tile pIeI ciltie r spoIses of 1mcanll splcnie blood flowx (SBF). ImeC.II imesentcrici blood fio (MBI3)I
miean rcinal bloodl flow (RB and mean illac blood i'lo (w BF ) to oi-aldel disteinsion ol ilhe Stomach altcr dli
'0010UtoXaminel in p (.1I
adminiistra tioni ofi 0r11 nolol 1IIInee pig g)strl distiension was a peril01med xwinh Rilngel
Soltitioln Volutiles ol()f 4 (). )( (0) a1nd (1 8 I (3).

Analy sis of v ariancc 1f)1 rcepeatcd measuirmnccts show ced a significlant dliflci-cncc in the
responscs of aill pcriphieral blood flows (at lea.Ist F = 9'6, P < 0(003). The Studenit NcwNman-
Keuls test indicattecl that the rcsponses to distension alfter the administration of pihentolamilnc
were signlificaiitly d'if'c-cit fr-om thlose obtained bcfori- and after tihe administration of'
propranolol for splcnic. rcnal and ililac blood flow\s andct that the rcsponse of imecsciter-ic bloodl
flowh after the administration of' phentolamineilld " as Sign11iificantly difl'cr-cent from tliat obtainecd
af'tcr tteiadministration of' propranolol.
Lperimewiirs fl/ter 1algotOmYV
Cervical vagotomly in the six, pigs claused an incr'eaISC in hieart rate (bca.ts mmiln l) of 1 2 + -35
(8 18) (P < 0(0005). This increase wxas accompanied by insignificant chang,cs in mean aCiortic
394 G. VACCA AND OTHERS
blood pressure and mean abdominal and iliac blood flows. Change in mean aortic blood
pressure (mmHg) was -92+ 17.3 (-32 to 18) (P > 010). Changes in blood flows (ml min-')
were: splenic, 18 + 29 (-20 to 56) (P > 0.05); mesenteric, -40+ 92 (-140 to 140) (P > 0.15);
renal, -21+ 28 (-61 to 17) (P > 0.05); and iliac, -1 + 7 (-7 to 14) (P > 0.35). During the
experiments performed after the intervention, gastric transmural pressure (mmHg) was
9 5+ 24(6-13).
Group changes in blood flow elicited by the distension are shown in Table 1. Bilateral
vagotomy completely abolished in each pig the responses of the regional blood flows
previously caused in the same animals by gastric distension. Changes in the other
haemodynamic variables during the experiments were insignificant (at least P > 020).
Analysis of variance for repeated measurements showed a significant difference in the
responses of all peripheral blood flows (at least F = 15 1, P < 00005). The Student-
Newman-Keuls test indicated that the responses to distension after vagotomy were
significantly different from those obtained before and after the administration of butoxamine
for splenic, renal and iliac blood flows and that the response of mesenteric blood flow after
vagotomy was significantly different from that obtained after the administration of
butoxamine.
DISCUSSION

The main findings of this work include, first, the definition of the reflex response of a decrease
in blood flow in regional vascular beds without interference from changes in arterial blood
pressure, heart rate ormechanisms
venous return. Second, it was shown that this reflex response involved
related to both a- and 3-adrenoceptors, depending on the
etferent sympathetic
vascular regions investigated, and the afferent vagal pathways. Third, the overall results
indicated the heterogeneous nature of efferent sympathetic responses.
In the present investigation, in which arterial blood pressure was kept constant, gastric
distension elicited significant decreases in splenic, renal and iliac blood flows. The prevention
of changes in arterial blood pressure and the absence of changes in right atrial pressure
excluded any significant interference by reflexes related to cardiovascular receptors and
indicated that stomach distension primarily caused splenic, renal and iliac vasoconstriction.
However, during the same distension experiments the response of mesenteric blood flow was
variable and insignificant: increases, decreases and no change were observed. When the
experiments were repeated after /3-blockade with propranolol or butoxamine, a decrease in
mesenteric blood flow and more marked decreases in the other measured flows occurred.
The results obtained after the administration of propranolol or butoxamine indicated that the
mechanisms of the responses of splenic, mesenteric, renal and iliac blood flows to gastric
distension were offset by a vasodilatation involving the 3-adrenoceptors. This finding
suggested a role for vasodilating /3-adrenoceptors in the control of the peripheral circulation of
the pigs during gastric distension and indicated that this role is quantitatively more important
in the superior mesenteric vascular bed. It is remarkable that the vasoconstrictive response was
greater despite the fact that administration of propranolol or butoxamine caused an increase in
the baseline values of aortic blood pressure and a decrease in the baseline values of the
measured regional blood flows. This finding raised two possibilities: either the /3-blockade
affected baseline vascular resistance or it potentiated the a-constrictive responses. However, it
is interesting to note from the present results that,B-adrenoceptors are likely to be present in
the pig despite reports that the human splanchnic vessels are devoid of ,-adrenoceptors
(Lebrec, 1990).
 STOMACH DISTENSION AND PERIPHERAL FLOW 395
The results obtained with the experiments performed after the administration of
phentolamine demonstrated that the vasoconstriction previously elicited by gastric distension
was mediated by a-adrenoceptors. This finding, together with the findings obtained after the
administration of propranolol or butoxamine, is consistent with previous evidence showing
that the cardiovascular responses to distension of the stomach in anaesthetized pigs involved
eflerent sympathetic mechanisms (Vacca & Vono, 1993; Vacca et al. 1994b) and indicated
that the responses of vasoconstriction could be attributed to activation of eflerent sympathetic
nerves.
The present study showed that the afferent limb of the reflex haemodynamic changes caused
by distension of the stomach in the examined regional vascular beds involved the vagus nerves.
This result is consistent with previous reports showing that the muscular layers of the stomach
contain mechanoreceptors which are stimulated by gastric distension and discharge into
afferent vagal nerve fibres (Paintal, 1954; Iggo, 1957; Falempin, Mei & Rousseau, 1978;
Cotterel & Iggo, 1984). Other receptors in the region of the stomach and the adjacent
mesentery which discharge into afferent fibres of the splanchnic nerves are thought to be
involved in nociception (Janig & Morrison, 1986; Grundy & Scratcherd, 1989) and control of
organ motility in animals such as dogs, cats and sheep (Janig & Morrison, 1986; Grundy &
Scratcherd, 1989). However, the sensation of pain is believed to be elicited when receptors are
excessively stimulated (Janig & Morrison, 1986), and may therefore depend on the intensity of
stimulation. In the present investigation, distension of the stomach elicited reflex responses
involving vagal afferent pathways and possibly the physiological regulation of the cardio-
vascular system. It is possible that these responses did not involve nociception, since the
pressures used (about 12 mmHg) have been reported not to stimulate gastric nociception
(Janig & Morrison, 1986). Also, electrical stimulation of subdiaphragmatic afferent vagal
fibres in rats has been demonstrated to elicit an intensity-dependent inhibition of pain
behaviour and of transmission of nociceptive impulse activity (Randich & Gebhart, 1992).
These observations suggest that the distension in the present experiments did not involve
nociception.
The present investigation further supports the heterogeneity of efferent sympathetic effects.
For instance, as in the case of gastric distension, distension of the descending colon has been
shown to cause reflex haemodynamic changes through efferent sympathetic mechanisms
(Cevese et al. 1992). Unlike stomach distension, however, distension of the colon also
increased left ventricular inotropic state and caused a marked reduction in the superior
mesenteric blood flow and had small or no effects on renal and iliac blood flow (Cevese et al.
1992; Cevese, Grasso, Poltronieri, Schena & Vacca, 1993). These observations may have
important implications. For instance, the reflex vasoconstrictive effect of distension of the
stomach would interact with the known postprandial hyperaemic effect in the mesenteric
circulation. It is of interest that the two effects are mediated by different mechanisms related to
the sympathetic nervous system and could reflect interactions between cardiovascular and
gastrointestinal systems control. These considerations support the view that the effects of
sympathetic innervation are heterogeneous, and also suggest that these effects could be
influenced further by the behaviour of the vascular beds of the target organs.
In conclusion, the present investigation showed that innocuous distension of the stomach in
anaesthetized pigs primarily caused reflex vasoconstriction in the splenic, renal and iliac
vascular beds; a reflex mesenteric vasoconstriction was also observed but only after
,/-blockade. These reflex responses were mediated by sympathetic mechanisms which involved
both a and , vascular adrenoceptors and their afferent limb was in the vagal nerves.
396 G. VACCA AND OTHERS

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