Hypoxic pulmonary vasoconstriction in reptiles: a
comparative study of four species with different lung
structures and pulmonary blood pressures
Nini Skovgaard, Augusto S. Abe, Denis V. Andrade and Tobias Wang
Am J Physiol Regul Integr Comp Physiol 289:1280-1288, 2005. First published Jun 16, 2005;
doi:10.1152/ajpregu.00200.2005
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Am J Physiol Regul Integr Comp Physiol 289: R1280 –R1288, 2005.
First published June 16, 2005; doi:10.1152/ajpregu.00200.2005.
Hypoxic pulmonary vasoconstriction in reptiles: a comparative study of four
species with different lung structures and pulmonary blood pressures
Nini Skovgaard,1 Augusto S. Abe,2 Denis V. Andrade,2 and Tobias Wang1
1
Department of Zoophysiology, University of Aarhus, Aarhus, Denmark;
and 2Departamento de Zoologia, Universidade Estadual Paulista, Rio Claro, São Paulo, Brazil
Submitted 21 March 2005; accepted in final form 14 June 2005
LOW OXYGEN LEVELS IN THE LUNGS of birds and mammals cause
constriction of the pulmonary vasculature that elevates resistance to pulmonary blood flow (Q̇pul) and increases pulmonary
blood pressure (3, 14, 43). This hypoxic pulmonary vasoconstriction (HPV) diverts Q̇pul from poorly ventilated and hypoxic areas of the lung to more well-ventilated parts. Therefore,
HPV is considered important for local matching of ventilation
to blood perfusion, which improves pulmonary gas exchange
and maintains arterial PO2 (4, 12, 43). The primary site of the
hypoxic vasoconstriction is the precapillary muscular pulmonary arteries (45).
HPV is a locally mediated response that persists in isolated
and perfused lungs with no neurohumoral influences and also
occurs in isolated rings of vascular smooth musculature (15,
37). The constriction is intrinsic to the vascular smooth muscle
surrounding the small resistance vessels and is likely to be
mediated by inhibition of one or several different types of K⫹
channels, with various endothelium-derived vasoactive compounds acting as modulators (25, 44, 45, 46). In contrast, the
systemic circulation of most vertebrates responds to hypoxia
by vasodilatation (10, 13, 38, 41).
The need for local matching of ventilation and perfusion is
likely to increase as the lung structure becomes more complex
(36). Hence, it is possible that, in the transition from the
structurally simple lungs of reptiles to more complex lungs in
mammals, local and humoral regulations of the pulmonary
circulation are increasingly important. In contrast to mammals,
the role of humoral and local factors in cardiovascular control
remains largely unknown in reptiles. Recent studies, nevertheless, indicate that the pulmonary circulation is much less
responsive to humoral and local factors than the systemic
circulation (8, 9, 11, 16, 35, 40).
Lung structure and heart morphology vary substantially
among reptiles. Most snakes and many lizards have unicameral
and simple lungs, whereas the multicameral lungs in turtles,
varanid lizards, and crocodilians are more complex and compartmentalized (26, 31, 32, 34). The higher complexity allows
for smaller gas exchange units and increased surface area,
which increases pulmonary diffusive capacity for O2 but may
also render the lungs more prone to local mismatching of
ventilation to perfusion [ventilation-perfusion (V̇A/Q̇) inhomogeneity] (36). Turtles exhibit HPV (10), but no other reptiles
have been studied. In most noncrocodilian reptiles, the ventricle is anatomically and functionally undivided, so blood pressures are equal in systemic and pulmonary circulations (e.g.,
Ref. 20). Therefore, blood flow distribution between pulmonary and systemic circulations is primarily determined by
pulmonary and systemic vascular resistances, respectively (10,
20), and HPV would increase the right-to-left cardiac shunt in
animals with an undivided heart. This would reduce the ability
to exploit the pulmonary oxygen reserve, which would be
further aggravated in animals with periodic ventilation, where
PO2 decreases in the lung during breath hold. Thus we hypothesize that HPV has evolved in groups of reptiles that have
functionally divided hearts and morphologically complex
lungs.
In the present study, the effects of acute hypoxia on pulmonary and systemic blood flows and pressures were measured in
four species of anesthetized reptiles with diverse lung struc-
Address for reprint requests and other correspondence: N. Skovgaard, Dept.
of Zoophysiology, University of Aarhus, Bldg. 131, DK-8000 Aarhus C,
Denmark (e-mail: [email protected]).
The costs of publication of this article were defrayed in part by the payment
of page charges. The article must therefore be hereby marked “advertisement”
in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
hypoxia; pulmonary circulation; systemic circulation
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0363-6119/05 $8.00 Copyright © 2005 the American Physiological Society
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Skovgaard, Nini, Augusto S. Abe, Denis V. Andrade, and
Tobias Wang. Hypoxic pulmonary vasoconstriction in reptiles: a
comparative study of four species with different lung structures
and pulmonary blood pressures. Am J Physiol Regul Integr Comp
Physiol 289: R1280 –R1288, 2005. First published June 16, 2005;
doi:10.1152/ajpregu.00200.2005.—Low O2 levels in the lungs of
birds and mammals cause constriction of the pulmonary vasculature
that elevates resistance to pulmonary blood flow and increases pulmonary blood pressure. This hypoxic pulmonary vasoconstriction
(HPV) diverts pulmonary blood flow from poorly ventilated and
hypoxic areas of the lung to more well-ventilated parts and is considered important for the local matching of ventilation to blood
perfusion. In the present study, the effects of acute hypoxia on
pulmonary and systemic blood flows and pressures were measured in
four species of anesthetized reptiles with diverse lung structures and
heart morphologies: varanid lizards (Varanus exanthematicus), caimans (Caiman latirostris), rattlesnakes (Crotalus durissus), and tegu
lizards (Tupinambis merianae). As previously shown in turtles, hypoxia causes a reversible constriction of the pulmonary vasculature in
varanids and caimans, decreasing pulmonary vascular conductance by
37 and 31%, respectively. These three species possess complex
multicameral lungs, and it is likely that HPV would aid to secure
ventilation-perfusion homogeneity. There was no HPV in rattlesnakes, which have structurally simple lungs where local ventilationperfusion inhomogeneities are less likely to occur. However, tegu
lizards, which also have simple unicameral lungs, did exhibit HPV,
decreasing pulmonary vascular conductance by 32%, albeit at a lower
threshold than varanids and caimans (6.2 kPa oxygen in inspired air
vs. 8.2 and 13.9 kPa, respectively). Although these observations
suggest that HPV is more pronounced in species with complex lungs
and functionally divided hearts, it is also clear that other components
are involved.
HYPOXIC PULMONARY VASOCONSTRICTION IN REPTILES
tures and heart morphologies: rattlesnakes (Crotalus durissus)
and tegu lizards (Tupinambis merianae), which possess an
undivided ventricle and a simple lung structure; caimans
(Caiman latirostris), which have an anatomically divided ventricle and complex lung structure; and varanid lizards (Varanus
exanthematicus), which possess functionally divided ventricles
and morphologically complex lungs. The study was performed
on anesthetized animals to reduce cardiovascular reflexes involving the central nervous system and therefore to reduce the
possibilities that the observed responses are due to stimulation
of, for example, vascular chemoreceptors. To investigate
whether changes in vagal tone on the pulmonary vasculature
(e.g., Refs. 5, 28) were altered during hypoxia, we characterized the hypoxic responses before and after a pharmacological
blockade of the muscarinic receptors by atropine.
MATERIALS AND METHODS
Experimental Animals
Anesthesia
Tegu lizards, rattlesnakes, and caimans were anesthetized with an
intramuscular injection of pentobarbital sodium (30 mg/kg for rattlesnakes and 50 mg/kg for tegu lizards and caimans; Mebumal, Sygehusapotekerne, Denmark). Corneal and pedal withdrawal reflexes
disappeared within 15– 45 min. Because of their low tolerance of
hypoxia, varanid lizards were rapidly anesthetized by inhalation of
isoflurane vapor (Isofluran, Baxter, Denmark) by placing a plastic bag
over their heads. During the initial surgery, the varanid lizards were
ventilated with room air containing 1% isoflurane; however, when the
first cannulation was finished, an intra-arterial injection of pentobarbital sodium (Mebumal; 50 mg/kg) was given, and the isoflurane was
turned off. Tegu lizards and caimans were intubated, whereas rattlesnakes and varanid lizards were traecheotomized for artificial ventilation using a Harvard Apparatus mechanical ventilator at 15–20
breaths/min and a tidal volume of 50 –100 ml/kg with 3% CO2balance air.
Surgery and Instrumentation
Because of anatomical differences among the different species and
because experiments were performed at different places, the surgeries
and instrumentation differed slightly between the four species.
Varanid lizards. To access the central vascular blood vessels, a
5-cm incision was made through the sternum. The left carotid artery
was occlusively cannulated with a PE-50 catheter containing heparinAJP-Regul Integr Comp Physiol • VOL
ized saline for measurement of systemic arterial blood pressure, and a
branch of the left pulmonary artery was occlusively cannulated (PE50) for measurement of pulmonary arterial blood pressure. Transittime ultrasonic blood flow probes (2S or 2R; Transonic System) were
placed around the left pulmonary arch and the left aortic arch for
measurements of blood flows.
Tegu lizards. A 5-cm ventral incision was made through the
sternum, leaving the pericardium intact. For measurement of pulmonary blood pressure, a branch of the left pulmonary artery was
occlusively cannulated, and a blood flow probe was placed around the
common pulmonary vein for measurement of total Q̇pul.
Rattlesnakes. A small incision was made cranial to the heart, and a
PE-50 catheter was advanced into the right aortic arch through the
vertebral artery for measurement of systemic blood pressure. For
measurement of pulmonary blood pressure, a small branch of the
pulmonary artery supplying the lower part of the lung was occlusively
cannulated. In addition, for measurement of right and left atrial
pressures (PLAt), the right atrium and left atrium were cannulated in
three animals using a flared PE-60 catheter containing heparinized
saline, which was advanced into the atrium through a small incision in
the atrial walls and secured with a suture. Transit-time ultrasonic
blood flow probes (2S or 2R; Transonic System) were placed around
the left aortic arch and the pulmonary artery.
Caimans. A 5-cm ventral incision was made through the sternum.
For measurement of systemic blood pressure, the right carotid artery
was occlusively cannulated using a PE-50 catheter containing heparinized saline. To measure pulmonary blood pressure, the common
pulmonary artery was nonocclusively cannulated with a flared PE-60
catheter advanced through a small incision in the artery wall and
secured with a suture. PRAt and PLAt, respectively were measured in
three animals using a flared PE-60 catheter, which was advanced into
the atrium through a small incision in the atrial walls and secured with
a suture. For measurements of blood flows, probes were placed around
the left pulmonary arch and the left subclavian artery.
All catheters were connected to disposable pressure tranducers
(model PX600; Baxter-Edwards, Irvine, CA), and signals were amplified by using an in-house-built preamplifier. Acoustical gel was
infused around the blood flow probes to enhance the signal. Flow
probes were connected to a Transonic dual-channel blood flow meter
(T206). The pressure transducers were positioned at the level of the
heart of the animal and were calibrated daily against a static water
column.
Signals from the pressure transducer and the blood flow meter were
recorded with a Biopac MP100 data-acquisition system (Biopac
Systems, Goleta, CA) at 100 Hz.
Calculation of Blood Flows, Stroke Volumes,
and Vascular Conductances
Measurements of blood flow in the common pulmonary vein in the
tegu lizard represent total Q̇pul. Because there is only one pulmonary
artery in the rattlesnake, measurements of blood flow in the pulmonary artery represents Q̇pul. Total systemic blood flow (Q̇sys) in the
rattlesnake can be estimated as 3.3 times blood flow in the left aortic
arch (17). Q̇pul in caimans and varanid lizards was calculated as two
times blood flow in the left pulmonary artery under the assumption
that Q̇pul is distributed evenly between the left and right pulmonary
artery. Total cardiac output was calculated as Q̇sys ⫹ Q̇pul. Heart rate
(fH) was calculated from the instantaneous blood flow trace, and total
stroke volume (pulmonary ⫹ systemic) was calculated as total cardiac
output/fH.
When baseline blood flow changes more than baseline blood
pressure, which is the case in most in vivo situations, conductance
provides a better index for comparing vascular tone than resistance
(24, 29). Pulmonary and systemic conductance (Gpul and Gsys, respectively) were calculated from mean blood flow and mean blood
pressure (Gpul ⫽ Q̇pul/Ppul and Gsys ⫽ Q̇sys/Psys, where Ppul and Psys
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Experiments were performed on six tegu lizards (Tupinambis
merianae), six rattlesnakes (Crotalus durissus), seven caimans
(Caiman latirostris), and seven varanid lizards (Varanus exanthematicus). The tegu lizards were captive bred at UNESP (Rio Claro, Brazil)
and freighted to the Department of Zoophysiology, University of
Aarhus (Aarhus, Denmark), where experiments were conducted. They
had body masses ranging between 0.83 and 3.0 kg (1.36 ⫾ 0.34 kg,
mean ⫾ SE). Varanid lizards with body masses between 0.33 and 1.02
kg (0.66 ⫾ 0.12 kg) were obtained from Danish commercial suppliers,
and experiments were performed at the University of Aarhus. Studies
on rattlesnakes and caimans were carried out at UNESP. Rattlesnakes
with body masses ranging from 0.53 to 1.5 kg (0.81 ⫾ 0.16 kg) were
obtained from the Butantan Institute (São Paulo, Brazil) and transported to UNESP. Caimans were captive bred at UNESP and had
body masses between 0.73 and 1.4 kg (0.94 ⫾ 0.08 kg). Rattlesnakes
were held in vivaria and caimans in outdoor open pens at 27 ⫾ 5°C,
with free access to water. Food was withheld 3 days before experiments. All animals appeared healthy, and experiments were carried
out according to Danish and Brazilian federal regulations.
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HYPOXIC PULMONARY VASOCONSTRICTION IN REPTILES
are pulmonary and systemic pressure, respectively), assuming that
central venous blood pressures are negligible.
Experimental Protocols
Data Analyses and Statistics
We analyzed data using AcqKnowledge data analysis software
(version 3.7.1; Biopac). Mean pressure and mean blood flow were
taken over a 3-min period, at the end of each period of treatment. All
data are presented as means ⫾ SE. Effects on hemodynamic variables
were assessed by a one-way ANOVA for repeated measures followed
by a Dunnett’s post hoc test to identify values that were significantly
different from values obtained during normoxia. Differences between
resting values and recovery values were assessed using paired t-tests.
A limit for significance of P ⬍ 0.05 was applied.
In the tegu lizards, hypoxia led to a decrease in Gpul from
7.2 ⫾ 0.9 to 4.9 ⫾ 1.3 ml䡠 min⫺1 䡠 kg⫺1 䡠 kPa⫺1 (32%) when
PIO2 was reduced to 6.2 kPa (Fig. 1C). This pulmonary constriction was reverted when the animals were returned to
normoxia (Fig. 1C). There were no changes in Ppul and Q̇pul,
but fH was significantly reduced at 6.2 kPa and did not recover
at return to normoxia (Fig. 1).
In the rattlesnakes, inhalation of hypoxic gas mixtures increased Gsys attended by a decrease in Psys and a rise in Qsys
(Fig. 2, A–C). The dilation, however, persisted on return to
normoxia. Hypoxia had no effect on Gpul, but there was a
decrease in Ppul and Q̇pul, indicating an increased right-to-left
cardiac shunt caused by the systemic vasodilatation (Fig. 2,
D–F). This is also apparent from the reduction in the shunt
fraction (Q̇pul/Q̇sys), which decreased from 0.8 ⫾ 0.2 to 0.4 ⫾
0.1 at 1.8 kPa (Fig. 3D). The fH increased progressively during
hypoxia, but there were no changes in total stroke volume or
total cardiac output (Fig. 3, A–C). Infusion of atropine, following the exposure to hypoxia, did not affect any of the hemodynamic variables in normoxia. During subsequent exposure to
hypoxia, most responses were not affected, but the progressive
decline in Psys and rise in Gsys were no longer manifested.
Table 1 shows the PRAt and PLAt in three rattlesnakes that
breathed normoxic air and then were exposed to progressive
levels of hypoxia. The low n values did not allow for statistical
analysis, but it appears that the atrial pressures remained
unchanged during hypoxia (mean PLAt of 0.52 ⫾ 0.01 kPa and
mean PRAt of 0.63 ⫾ 0.01 kPa).
In the caimans, Psys decreased during hypoxia, although
there were no changes in left subclavian blood flow, Gsys, and
fH (Figs. 4, A–C, and 5). Hypoxia caused a pulmonary vasoconstriction, apparent as a decrease in Gpul from 12.9 ⫾ 1.9 to
Fig. 1. Effects of hypoxia on the pulmonary circulation in the tegu lizard (Tupinambis merianae).
Pulmonary arterial blood pressure (Ppul; A), pulmonary blood flow (Q̇pul; B), pulmonary vascular conductance (Gpul; C), heart rate (fH; D), and inspired
PO2 (PIO2) results are shown. *Significantly different
from the normoxic results; †significant difference
between recovery values and initial normoxic values
(P ⬍ 0.05). Values are means ⫾ SE (n ⫽ 6).
AJP-Regul Integr Comp Physiol • VOL
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During experiments, the animals were artificially ventilated using a
Harvard Apparatus mechanical ventilator at 15–20 breaths/min and a
tidal volume of 50 –100 ml/kg. Because the animals were hyperventilated, PCO2 of inspired air was maintained at 0.03 kPa during all
experiments to keep arterial pH constant. Gases of desired composition were delivered to the ventilator by a Cameron Instrument gas
mixer or a Wösthoff (Bochum, Germany) gas-mixing pump. Hemodynamic variables stabilized over a period of 30 – 45 min after
instrumentation, and the animals were then exposed to progressive
levels of hypoxia through a reduction in PO2 of inspired air (PIO2)
(tegu lizard: 13.7, 10.3, 8.2, 6.2 kPa; varanid lizards: 13.9, 10.3, 8.2,
6.2, 5.6 kPa; rattlesnakes and caimans: 13.9, 9.2, 7.4, 5.5, 3.7, 1.8
kPa). Each gas mixture was administered for 20 min, and the animals
were then returned to normoxia.
After hypoxic exposures, atropine (3 mg/kg) was administered
through the systemic catheter in caimans and rattlesnakes and was
allowed to take effect for 30 min. The lowest levels of hypoxia
(rattlesnakes: 3.7, 1.8 kPa; caimans: 5.5, 3.7, 1.8 kPa) were then
repeated. Experiments were carried out at 25 ⫾ 3°C.
RESULTS
HYPOXIC PULMONARY VASOCONSTRICTION IN REPTILES
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8.9 ⫾ 0.6 ml䡠 min⫺1 䡠 kg⫺1 䡠 kPa⫺1 (31%); this was attended by
an increase in Ppul, whereas Q̇pul remained stable (Fig. 4, D–F).
The threshold for the vasoconstriction was 13.9 kPa. Infusion
of atropine did not affect hemodynamic variables in normoxia
and during subsequent exposure to hypoxia.
Table 2 shows that PLAt in three caimans did not change in
normoxic air and progressive hypoxia.
In the varanid lizards, hypoxia decreased Psys and fH,
whereas there were no changes in blood flow in the left aortic
arch or Gsys (Figs. 6, A–C, and 7). Psys and fH did not recover
when the animals were put back on normoxia. Hypoxia elicited
a decrease in Gpul from 16.8 ⫾ 3.3 to 10.6 ⫾ 1.8 ml䡠 min⫺1 䡠
kg⫺1 䡠 kPa⫺1 (37%) followed by a decrease in Q̇pul but no
changes in Ppul (Fig. 6, D–F). The threshold for HPV was 8.2
kPa, and Gpul recovered to basal values when the lizards were
returned to normoxic air.
DISCUSSION
The present study describes HPV in four different species of
reptiles with different lung structure and heart morphologies.
These species were selected to investigate the hypothesis that
HPV is most pronounced in reptilian species with structurally
complex lungs where V̇A/Q̇ inequalities are more likely to
AJP-Regul Integr Comp Physiol • VOL
occur. At the same time, we hypothesized that animals with an
undivided ventricle, where the blood flow distribution between
the systemic and pulmonary circulations is determined by the
vascular resistances and constriction of the pulmonary vasculature would induce a right-to-left cardiac shunt, are less likely
to exhibit HPV.
As previously shown in turtles (10), hypoxia caused a
reversible constriction of the pulmonary vasculature in varanids and caimans. These three species possess complex
multicameral lungs where HPV would aid to secure V̇A/Q̇
homogeneity. There was no response in rattlesnakes, which is
consistent with the view that species with structurally simple
lungs are less prone to V̇A/Q̇ inhomogeneities and therefore are
less dependent on local responses for proper V̇A/Q̇ matching.
However, tegu lizards that also have simple unicameral lungs
did exhibit HPV, albeit at a lower threshold than varanids and
caimans. Thus, although the data support our general hypothesis that HPV is more pronounced in species with complex
lungs and divided hearts, it is also clear that other factors are
involved.
In mammals, it is well established that HPV is locally
mediated and that the primary site of constriction is the small
resistance arteries (15, 37, 46). In reptiles, Gpul can also be
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Fig. 2. Effects of hypoxia before and after a
bolus injection of atropine (3 mg/kg) on hemodynamic parameters in the rattlesnake (Crotalus
durissus). Systemic arterial blood pressure (Psys;
A), systemic blood flow (Q̇sys; B), systemic
vascular conductance (Gsys; C), Ppul (D), Q̇pul
(E), Gpul (F), and PIO2 results are shown. *Significantly different from the normoxic results;
†significant difference between recovery values
and initial normoxic values (P ⬍ 0.05). Values
are means ⫾ SE (n ⫽ 6).
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HYPOXIC PULMONARY VASOCONSTRICTION IN REPTILES
Fig. 3. Effects of hypoxia before and after a bolus
injection of atropine (3 mg/kg) on hemodynamic
parameters in the rattlesnake (C. durissus). Shown
are fH (A), total stroke volume (VStot; B), total
cardiac output (Q̇tot; C), shunt fraction (Q̇pul/Q̇sys;
D), and PIO2 results. *Significantly different from
the normoxic results; †significant difference between recovery values and initial normoxic values (P ⬍ 0.05). Values are means ⫾ SE (n ⫽ 6).
Table 1. Left and right atrial pressures measured in the
rattlesnake, Crotalus durissus, when breathing normoxic
air and then progressive levels of hypoxia
PO2, kPa
PLAt, kPa
PRAt, kPa
n
19.3
13.9
9.2
7.4
5.5
3.7
1.8
0.54
0.48
0.49
0.49
0.55
0.59
0.52
0.60
0.59
0.61
0.63
0.68
0.65
0.62
3
2
2
2
2
3
3
PLAt and PRAt, left and right atrial pressure, respectively.
AJP-Regul Integr Comp Physiol • VOL
Critique of Methods
To calculate vascular conductance as conductance ⫽ flow/
pressure, we assumed that central venous pressures are negligible. This assumption is potentially problematic in low pressure systems and could underestimate systemic and pulmonary
conductances if atrial pressures are high: the higher the atrial
pressures, the higher the conductances (2). We measured PLAt
in three rattlesnakes and three caimans (Tables 1 and 2). In
caimans, the PLAt of 0.7 kPa does significantly underestimate
Gpul; however, because it was only measured in three of the
seven animals, we did not subtract PLAt in the calculation of
Gpul. Importantly, PLAt did not change during hypoxia in either
caimans or rattlesnakes; therefore, the changes in Gpul in
response to hypoxia are not due to altered atrial pressures but
a change within the pulmonary circulation.
HPV in Reptiles
Both varanid lizards and caimans have functionally divided
ventricles with mammalian-like high pressures in the systemic
circulation and low pulmonary pressures (7, 23); furthermore,
they have highly complex multicameral lungs with multiple
subdivisions, but a fairly shallow edicular respiratory parenchyma (32, 33, 34). In both species, hypoxia elicited a 35%
decrease in Gpul, which led to an increase in pulmonary
pressure in the caiman, whereas Q̇pul decreased in the varanid
lizards. Millard and Johansen (27) previously showed that
pulmonary arterial pressure increases when nonanesthetized
Varanus niloticus were breathing hypoxic gases. In our experiment, the threshold for the response was lower in the varanids
compared with the caimans (8 –10 and 14 kPa PIO2, respectively). The threshold for the caiman is certainly within the
range of normal lung PO2 values during breath hold (e.g., Refs.
18, 19). Anesthetized turtles (Trachemys scripta) also exhibit a
marked HPV, but this response only occurred in severe hyp289 • NOVEMBER 2005 •
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altered through a vagally mediated constriction of the pulmonary artery (e.g., Refs. 5, 28); however, vagal tone is normally
low or even absent in reptiles anesthetized with barbiturates
(e.g., Refs. 10, 16). Furthermore, because the hypoxic responses persisted after muscarinic receptor blockade by atropine in caimans (Fig. 4F) and in turtles (10), it is reasonable to
conclude that the decrease in Gpul during hypoxia in our study
does reflect a local vasoconstriction of resistance vessels in
response to low oxygen.
In mammals, it is well documented that acute exposure to
hypoxia causes a sustained rise in pulmonary arterial pressure
(42). Nevertheless, it is conductance of the pulmonary vasculature that is the determining factor. In fact, pressure alone
cannot reveal HPV because cardiac contractility or other factors could affect pulmonary pressure without conductance
being changed. Furthermore, in reptiles, where the ventricle of
most species is undivided, pulmonary pressure is also determined by systemic resistance. Thus, during hypoxia, when the
systemic vasculature normally dilates, it is quite conceivable
that pulmonary pressure could decline, even though this part of
the pulmonary circulation constricts.
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HYPOXIC PULMONARY VASOCONSTRICTION IN REPTILES
oxia (1.5–3 kPa PIO2) (10). Turtles have structurally complex
lungs (31), but, contrary to the caimans and varanid lizards,
their ventricles are undivided, and HPV, accordingly, increases
the right-to-left cardiac shunt (10). During normoxia, V̇A/Q̇
inhomogeneity decreases with increased Q̇pul in anesthetized
turtles (21); therefore, it is possible that the lower pulmonary
blood flow that occurs as a consequence of HPV could, in
itself, affect V̇A/Q̇ matching.
The rattlesnake and the tegu lizard have undivided ventricles
and, consequently, equal pressures in systemic and pulmonary
circulation (Ref. 16; N. Skovgaard and T. Wang, unpublished
observations on tegus). Their lungs are unicameral with a
central air-filled cavity that opens radially into the parenchyma
(26, 32). The faveolar parenchyma has deep honeycombshaped respiratory units, which are heterogeneously dispersed
in the lung (26, 32). Although the gross anatomy of these lungs
Table 2. Left atrial pressure measured in the caiman,
Caiman latirostris, when breathing normoxic air and
progressive levels of hypoxia
Fig. 5. Effects of hypoxia before and after a bolus injection of atropine (3
mg/kg) on fH in the caiman (Caiman latirostris). Values are means ⫾ SE (n ⫽
7). P ⬍ 0.05.
AJP-Regul Integr Comp Physiol • VOL
PO2, kPa
PLAt, kPa
n
19.3
13.9
9.2
7.4
5.5
3.7
1.8
0.70
0.70
0.71
0.67
0.67
0.68
0.72
3
3
3
3
3
3
3
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Fig. 4. Effects of hypoxia before and after a
bolus injection of atropine (3 mg/kg) on hemodynamic parameters in the caiman (Caiman
latirostris). Psys (A), left subclavian blood flow
(Q̇lsub; B), Gsys (C), Ppul (D), Q̇pul (E), Gpul (F),
and PIO2 results are shown. *Significantly different from the normoxic results; †significant
difference between recovery values and initial
normoxic values (P ⬍ 0.05). Values are
means ⫾ SE (n ⫽ 7).
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HYPOXIC PULMONARY VASOCONSTRICTION IN REPTILES
is simple, the respiratory parenchyma is structurally complex,
and it is possible that the HPV expressed in the tegu lizards
represent local regulation of blood flows within individual
faveoli. In this case, HPV may be expressed in the tegus but not
Fig. 7. Effects of hypoxia on fH in the varanid lizard (Varanus exanthematicus). *Significantly different from the normoxic results; †significant difference
between recovery values and initial normoxic values (P ⬍ 0.05). Values are
means ⫾ SE (n ⫽ 7).
AJP-Regul Integr Comp Physiol • VOL
in the rattlesnakes because of their relatively higher maximal
metabolic rates (1, 22). In any event, the very low threshold of
the HPV (6 kPa O2) is close to the minimum level of PIO2 that
tegu lizards can tolerate (39).
Powell and Hopkins (36) recently reviewed V̇A/Q̇ distributions, measured by the multiple inert gas elimination technique,
in vertebrates. Surprisingly, they observed that some species
with structurally simple lungs, such as the tegu lizard, were
characterized by high inhomogeneity compared with reptiles
with high complexity. It is possible that the low threshold for
HPV in tegus may contribute to the relatively high V̇A/Q̇
inhomogeneity. Along these lines, it would be of interest to
investigate whether other local vasoactive substances (e.g.,
regulatory peptides and metabolites) exert stronger effects in
species with complex lungs.
Although increased lung complexity is likely to require HPV
for V̇A/Q̇ matching, other structural and physiological aspects
are also likely to determine whether HPV is expressed. Many
reptiles, particularly aquatic species, have an intermittent
breathing pattern with long periods of breath hold where lung
and blood PO2 decline (e.g., Ref. 6). If the heart is undivided,
HPV during long breath holds would induce right-to-left cardiac shunts where the pulmonary circulation is bypassed,
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Fig. 6. Effects of hypoxia on hemodynamic
parameters in the varanid lizard (Varanus exanthematicus). Psys (A), left aortic blood flow
(Q̇LAo; B), Gsys (C), Ppul (D), Q̇pul (E), Gpul (F),
and PIO2 results are shown. *Significantly different from the normoxic results; †significant
difference between recovery values and initial
normoxic values (P ⬍ 0.05). Values are
means ⫾ SE (n ⫽ 7).
HYPOXIC PULMONARY VASOCONSTRICTION IN REPTILES
which would reduce the ability to exploit pulmonary oxygen
stores. This may explain the low threshold for HPV in turtles
compared with caimans and the tegu and varanid lizards. Lung
oxygen stores, however, can be fully exploited during breath
hold if the heart is functionally divided, which may explain
why caimans exhibit HPV at very modest hypoxia. In animals
with a divided heart, HPV during breath hold will, nevertheless, cause pulmonary hypertension that may disturb pulmonary fluid balance (47). It is not surprising, therefore, that
varanid lizards that normally have a continuous breathing
pattern and that are unlikely to experience environmental
hypoxia exhibit strong HPV.
Responses of the Systemic Circulation to Hypoxia
GRANTS
This study was supported by the Danish Research Council and Fundação de
Amparo a Pesquisa do Estado de São Paolo.
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In rattlesnakes, hypoxia induced a dilation in the systemic
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