From the Department of Physiology (P.M., A.A., J.M.V., M.A., S.L.) and
the Department of Surgery (J.B.M.-L., E.O.), University of Valencia (Spain).
Correspondence to S. Lluch, MD, Department of Physiology, Facultad de Medicina y Odontología, Avda Blasco Ibáñez 17, 46010 Valencia, Spain. E-mail medinap{at}post.uv.es
Methods and Results—Saphenous vein rings were obtained from 32
patients undergoing coronary artery bypass surgery. The vein
rings were suspended in organ bath chambers for isometric
recording of tension. AVP (3x10-9 mol/L) enhanced
the contractions elicited by electrical field stimulation at 1, 2, and
4 Hz (by 80%, 70%, and 60%, respectively) and produced a leftward
shift of the concentration-response curve to norepinephrine
(half-maximal effective concentration decreased from
6.87x10-7 to 1.04x10-7 mol/L;
P<.05). The V1 vasopressin receptor
antagonist d(CH2)5Tyr(Me)AVP
(10-6 mol/L) prevented the potentiation evoked by AVP. The
selective V1 receptor agonist [Phe,2
Orn8]-vasotocin (3x10-9 mol/L) induced
potentiation of electrical stimulation–evoked responses, which was
also inhibited in the presence of the V1 receptor
antagonist (10-6 mol/L). In contrast, the
V2 receptor agonist desmopressin (10-9 to
10-7 mol/L) did not modify neurogenic responses, and the
V2 receptor antagonist
[d(CH2)5, D-Ile,2
Ile,4 Arg8]-vasopressin (10-8 to
10-6 mol/L) did not prevent the potentiation induced by
AVP. The dihydropyridine calcium
antagonist nifedipine (10-6 mol/L)
did not affect the potentiating effect of AVP.
Conclusions—The results suggest that low concentrations of AVP
facilitate sympathetic neurotransmission and potentiate constrictor
effects of norepinephrine in human saphenous veins. These
effects appear to be mediated by V1 receptor stimulation
and are independent of calcium entry through
dihydropyridine calcium channels. Thus, AVP may
contribute to vascular mechanisms involved in acute ischemic
syndromes associated with venous grafts, particularly if the
sympathetic nervous system is activated.
AVP may also modify the effects of other vasoactive substances that are
found in plasma or released from perivascular nerve endings. Several
studies in various animal species have reported a significant
augmentation by AVP of the vasoconstricting action of
catecholamines.15 16 17 However, in
other studies, AVP did not change the constrictor activity of the
peripheral sympathetic nervous
system.18 In the human forearm, AVP attenuates
phenylephrine-induced
vasoconstriction,19 whereas recent experiments in
human isolated mesenteric arteries show that AVP enhances
adrenergic-mediated responses.20 Currently, there
is no information concerning the modulating effects of AVP on human
veins. A recent report from our laboratory indicates that AVP exerts
low contractile effects on human saphenous veins compared with human
arteries,21 thus suggesting that these veins may
have a low population or sensitivity of receptor sites for this
peptide. However, this does not exclude the possibility that AVP could
importantly affect vascular tone if this peptide would facilitate
sympathetic neurotransmission or sensitize the vascular smooth muscle
to the effects of norepinephrine. This might have important
implications in our understanding of the detrimental effects associated
with acute ischemic syndromes after autologous grafts in the
arterial circulation or coronary bypass
surgery.22 23 24 Accordingly, the objective of this
investigation was to determine whether low concentrations of AVP could
modify the constrictor responses to adrenergic stimulation of human
saphenous veins. We also determined whether the modulating effect of
AVP on vascular responsiveness depends on activation of
V1 or V2 receptors.
Two stainless steel L-shaped pins 200 µm in diameter were
introduced through the lumen of the vein ring. One pin was fixed to the
wall of the organ bath, and the other was connected to a
force-displacement transducer (Grass FT03). Changes in isometric force
were recorded on a Grass polygraph (model 7). Each vein ring was
set up in a 4-mL bath that contained modified Krebs-Henseleit solution
of the following millimolar composition: NaCl 115, KCl 4.6,
MgCl2 · 6H2O 1.2,
CaCl2 2.5, NaHCO3 25,
glucose 11.1, and disodium EDTA 0.01. The solution was equilibrated
with 95% oxygen and 5% carbon dioxide to a pH of 7.3 to 7.4.
Temperature was held at 37°C. To establish the resting tension for
maximal force development, a series of preliminary experiments was
performed on vein rings of similar length and outer diameter that were
exposed repeatedly to 100 mmol/L KCl. Basal tension was increased
gradually until contractions were maximal. The optimal resting tension
was 3 g. The vein rings were allowed to attain a steady level of
tension during a 2- to 3-hour accommodation period before testing.
Functional integrity of the endothelium was confirmed
routinely at the beginning of the experiment by the presence or absence
of relaxation induced by acetylcholine (10-7 to
10-6 mol/L) or substance P
(10-9 mol/L) during contraction obtained with
norepinephrine (10-7 to
3x10-7 mol/L).
Electrical field stimulation was provided by a Grass S88 stimulator via
two platinum electrodes positioned on each side and parallel to the
axis of the vein ring. To assess the nature of the contractile
responses and to avoid direct stimulation of the smooth muscle,
frequency-response relationships were determined on a group of veins in
the presence and absence of 10-6 mol/L
tetrodotoxin following previously described
procedures.25 In summary, the protocol was
designed to find the optimal stimulation parameters (15 V,
0.2-ms duration) causing a contractile response that was completely
eliminated by 10-6 mol/L tetrodotoxin.
Frequency-response relationships were determined with 15-second trains
of pulses at 1, 2, and 4 Hz. A period of 10 minutes was allowed between
stimulations. The preparations were allowed to equilibrate for at least
10 minutes before they were incubated with tetrodotoxin
(10-6 mol/L) or prazosin
(10-6 mol/L). After 10 to 15 minutes of
incubation with the antagonist, a second set of
stimulations was performed. In each experiment, a second
frequency-response relationship in untreated vein rings was run in
parallel.
To study the effects of AVP on electrical field stimulation–induced
responses, frequency-response relationships were determined in a
separate group of experiments. After an initial set of stimulations,
the vein rings were consecutively incubated with increasing
concentrations of AVP (10-10 to
3x10-9 mol/L) for 10 minutes before another set
of stimulations was given. As a control, four consecutive sets of
stimulations were given to a group of untreated vein rings at identical
intervals. Less than 10% variability in the magnitude of electrical
field stimulation–induced contractions was observed for a given ring
during four consecutive sets of control stimulations.
In another series of experiments, after a first frequency-response
relationship was obtained, the preparations were incubated with either
the V1 receptor antagonist
d(CH2)5Tyr(Me)AVP
(10-6 mol/L), the V1
receptor antagonist (10-8 to
10-6 mol/L) plus AVP
(3x10-9 mol/L), the selective
V1 receptor agonist [Phe,2
Orn8]-vasotocin (10-10 to
3x10-9 mol/L), the V1
receptor antagonist (10-6 mol/L)
plus the V1 receptor agonist
(3x10-9 mol/L), the V2
vasopressin agonist desmopressin (10-9 to
10-7 mol/L), the V2
receptor antagonist
[d(CH2)5,
D-Ile,2 Ile,4
Arg8]-vasopressin (10-8
to 10-6 mol/L) plus AVP
(3x10-9 mol/L), or the reuptake blocker cocaine
(10-6 mol/L) plus AVP
(3x10-9 mol/L). After 10 to 15 minutes of
incubation with the corresponding drug, a second set of stimulations
was then performed. In each group of experiments, stimulations without
any treatment were run in parallel.
Concentration-response curves for norepinephrine
(10-9 to 3x10-5 mol/L)
and KCl (5 to 120 mmol/L) were determined in a cumulative manner.
Control (in the absence of AVP) and experimental (in the presence of
AVP) data were obtained from separate vascular preparations. Another
group of vein rings was incubated with the V1
receptor antagonist (10-6 mol/L)
plus AVP (3x10-9 mol/L) before exposure to
norepinephrine or KCl.
In another group of experiments, electrical field stimulation was
carried out under control conditions followed by a second set of
stimulations in the presence of nifedipine
(10-6 mol/L); then a third set of stimulations
was performed in the presence of nifedipine plus AVP
(3x10-9 mol/L). Frequency-response curves
without any treatment were run in parallel. In another group of veins,
norepinephrine (10-9 to
3x10-5 mol/L) was applied in the presence of
either nifedipine (10-6 mol/L) or
nifedipine plus AVP (3x10-9 mol/L),
and the data were compared with those obtained from untreated (control)
segments.
Drugs
Data Analysis
Effects of Electrical Stimulation
AVP (10-11 to 3x10-11
mol/L) did not change the contractions to electrical stimulation at the
frequencies used (1, 2, and 4 Hz). At higher concentrations
(10-10 to 3x10-9 mol/L),
AVP caused potentiation of the electrically evoked responses (Fig 1A
The selective V1 receptor agonist
[Phe2, Orn8]-vasotocin
induced a potentiation of electrical stimulation–evoked responses of a
magnitude similar to that observed in the presence of AVP. This
potentiation was also inhibited in the presence of the
V1 receptor antagonist
d(CH2)5Tyr(Me)AVP
(10-6 mol/L) (Fig 2A
To determine whether V2 receptors are involved in
the effects of AVP on field electrical stimulation, frequency-response
relationships were obtained in the absence and in the presence of the
V2 receptor antagonist
[d(CH2)5,
D-Ile2 , Ile4 ,
Arg8]-vasopressin. Fig 2B
Blockade of neuronal catecholamines reuptake by cocaine
(10-6 mol/L) had no effect on the potentiating
effects of AVP on electrical field stimulation (Fig 2C
Effect of AVP on Norepinephrine- and KCl-Induced
Contraction
AVP and Calcium
Previous studies have suggested the existence of
V2 receptors in some vascular beds that could
mediate vasodilatation. Administration of either
V2 receptor agonists or vasopressin during
V1 receptor blockade increased blood flow in some
vascular beds and decreased peripheral resistance in both
humans and dogs.11 12 13 In the human saphenous
vein, both AVP and the V2 receptor agonist
desmopressin cause relaxation that seems largely dependent on the
release of dilating prostaglandins.21
Therefore, we examined the potential role of V2
receptor stimulation in the enhancing effects of AVP. The results do
not support the intervention of V2 receptors in
these responses. First, the selective V2 receptor
agonist desmopressin did not modify responses to electrical field
stimulation. On the other hand, the V2 receptor
antagonist
[d(CH2)5,
D-Ile,2 Ile,4
Arg8]-vasopressin did not affect the
potentiation induced by AVP. In contrast, the selective
V1 receptor antagonist
d(CH2)5Tyr(Me)AVP inhibited
the amplifying effects of AVP on electrical field stimulation and
norepinephrine-induced contractions in a
concentration-dependent manner. In addition, the selective
V1 receptor agonist [Phe,2
Orn8]-vasotocin induced potentiating effects
similar to those observed in the presence of AVP. Therefore, the
results exclude a role for V2 receptors in the
potentiating effects of AVP and are consistent with the
hypothesis that V1 receptor stimulation in the
absence of direct contraction is followed by enhancement of responses
to both endogenous and exogenous
norepinephrine.
It might be conceived that the effects of AVP on electrical field
stimulation contractions could involve an effect on adrenergic nerves,
leading to release of norepinephrine, or alternatively AVP
could act with norepinephrine at postjunctional receptor
sites. Because norepinephrine release was not measured in
this study, a contribution of presynaptic facilitating effects cannot
be excluded. The fact that the concentration-response curve to AVP was
not modified by prazosin, an
We also considered the possibility that stimulation of
V1 receptors may facilitate calcium entry through
dihydropyridine calcium channels. Our results show
that nifedipine did not affect the direct contractions of
AVP or prevent the potentiating action of AVP on
norepinephrine- and electrical field stimulation–induced
contractions. This indicates that influx of extracellular calcium
through dihydropyridine-sensitive calcium channels
does not importantly contribute to the direct contractile effects of
AVP or participate in the potentiating effect of AVP on adrenergic
contractions. In line with that interpretation, our results show that
AVP did not affect the concentration-response curve to KCl, an agent
that induces contraction by facilitating calcium entry through
voltage-dependent calcium channels. Other mechanisms of calcium
handling such as an increase in inositol phosphate
metabolism and/or increase calcium release from
intracellular reservoirs1 26 27 may be involved
in the potentiating effects of AVP. In contrast, in human mesenteric
arteries, AVP brings about a facilitation of extracellular
Ca2+ entry by KCl through voltage-dependent
calcium channels.20 The precise explanation for
such tissue specificity is not known, but it may be due to differences
in distribution and pharmacological properties of
V1 vascular receptors between mesenteric arteries
and saphenous veins.
In contrast to the present results, Hilgers et
al18 did not find any effect of AVP on
sympathetic transmission in an in vitro perfused rat hind limb
preparation. A common finding in the vascular effects of this peptide
is the heterogeneity of responsiveness depending on
regional and species differences28 29 and may be
due to different populations or sensitivity of receptor sites for
AVP.6 8 30 In addition, Hilgers et
al18 used only one concentration of AVP (0.3
nmol/L), which probably was insufficient to modulate neurogenic
responses. Because the present findings show that the potentiating
effects of AVP are concentration dependent, it is conceivable that
differences between the concentrations of AVP used may also account for
the discrepant findings of our study and those of Hilgers et
al.18
Some of the present observations may be of clinical significance.
Several reports indicate that large arteries and veins from various
animal species may synthesize and store an AVP immunoreactive material
that appears identical to authentic AVP, thus suggesting that the
vascular peptide is of local rather than neurohypophysial
origin.31 32 This raises the possibility that
locally released AVP may reach concentrations high enough to act
synergistically with the adrenergic neurotransmitter. The concentration
of AVP in this study may be lower than those expected to occur in
response to hypotension, dehydration, and exercise and in some patients
with hypertension or congestive heart
failure.33 34 35 Consequently, the amplifying
effect of AVP on adrenergic-mediated constriction, shown in the
present experiments, may importantly contribute to vascular
mechanisms involved in acute ischemic syndromes associated with
venous grafts. The human saphenous vein can undergo spasm, which is a
clinically relevant problem, immediately after autologous grafts in the
arterial circulation or coronary bypass
surgery.22 23 24 In view of the specificity and
potency of the V1 antagonist
d(CH2)5Tyr(Me)AVP, it seems
appropriate to consider the use of V1 receptor
antagonists in circumstances in which AVP plasma
concentrations are raised. Furthermore, provided that
V1 receptor blockade is present, AVP induces
marked dilatation of previously contracted human
arteries5 and saphenous
veins,21 probably because of the release of
vasodilatory prostaglandins from the vessel wall. These
findings could explain the reduction of vascular resistance that has
been observed after intravenous administration of the
V1 antagonist
d(CH2)5Tyr(Me)AVP in
patients with hypertension or congestive heart failure in the presence
of high plasma AVP levels.34 36
In conclusion, the results of the present study demonstrate that
AVP, in addition to its direct vasoconstrictor effect, strongly
potentiates the contractions of human saphenous veins to
norepinephrine and stimulation of perivascular sympathetic
nerves. Both the direct and indirect effects of AVP appear to be
mediated by V1 receptor stimulation. The
potentiation induced by AVP is not related to activation of
dihydropyridine-sensitive calcium channels.
Received July 18, 1997;
revision received October 16, 1997;
accepted November 3, 1997.
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© 1998 American Heart Association, Inc.
Clinical Investigation and Reports
Arginine Vasopressin Enhances Sympathetic Constriction Through the V1 Vasopressin Receptor in Human Saphenous Vein
Abstract
Top
Abstract
Introduction
Methods
Results
Discussion
References
Background—Arginine vasopressin
(AVP) not only acts directly on blood vessels through V1
receptor stimulation but also may modulate adrenergic-mediated
responses in animal experiments in vivo and in vitro. The aim of the
present study was to investigate whether AVP can contribute to an
abnormal adrenergic constrictor response of human saphenous
veins.
Key Words: veins • arginine vasopressin • electrical stimulation • norepinephrine
Introduction
Top
Abstract
Introduction
Methods
Results
Discussion
References
Arginine vasopressin
(AVP) is a neuropeptide that promotes reabsorption of water in renal
tubular cells through V2 receptors and produces
constriction of vascular smooth muscle through V1
receptors.1 2 3 In human vessels, AVP causes
powerful V1 receptor–mediated constriction in
isolated mesenteric,4 5
cerebral,6 7 and renal8
arteries. This effect is endothelium independent and
due to direct stimulation of receptors located on smooth muscle
cells.5 9 10 Further studies of the
physiological effects of AVP have implicated a
possible role of V2 receptors in mediating
vasodilation in some vascular beds.11 12 13 14
Methods
Top
Abstract
Introduction
Methods
Results
Discussion
References
Vein segments were taken from portions of human saphenous veins
of patients undergoing coronary artery bypass surgery (32
patients; 23 men and 9 women; age range, 52 to 71 years). The study was
approved by the ethical committee of our institution, and informed
consent was obtained from each patient before the study. During
surgical preparation of the saphenous vein, the dilation procedure was
avoided. The veins were immediately placed in chilled Krebs-Henseleit
solution, and rings 3 mm long were cut for isometric
recording of tension.
The following drugs were used: tetrodotoxin,
nifedipine, prazosin, norepinephrine
hydrochloride, acetylcholine chloride, AVP acetate salt,
[(1-(ß-mercapto-ß,ß-cyclopentamethylenepropionic
acid)-2-(O-methyl)-tyrosine, 8-arginine) vasopressin]
[d(CH2)5Tyr(Me)AVP],
deamino-8-D-arginine vasopressin (desmopressin), substance
P acetate salt (Sigma Chemical Co), [Phe,2
Orn8]-vasotocin,
[d(CH2)5,
D-Ile,2 Ile,4
Arg8]-vasopressin (Peninsula Laboratories
Europe), and cocaine chlorhydrate (Abelló). All drugs were
dissolved in Krebs-Henseleit solution except nifedipine,
which was dissolved initially in ethanol and further diluted in Krebs
solution to the proper final concentration. Drugs were added to the
organ bath in volumes of <70 µL. Stock solutions of the drugs were
freshly prepared every day and kept on ice throughout the
experiment.
All values are expressed as mean±SE. Contractions are reported
in absolute tension (grams) or as a percentage of response to KCl
(100 mmol/L). EC50 values (concentrations of
agonist producing half-maximal contraction) were determined from
individual concentration-response curves by nonlinear regression
analysis, and from these values the geometric means were
calculated. The EC50 values were compared by an
unpaired t test and an ANOVA with Scheffé's test as
post hoc test. The number of rings taken from each patient varied from
8 to 16. Concentration-response curves of the tested agonists or
frequency-response relationships were performed in the presence and
absence of either AVP or the antagonists in rings obtained
from the same patient; the responses obtained in each patient were
averaged to yield a single value. Therefore, all number (n) values are
presented as the number of patients from whom the blood vessel
were obtained. For electrical stimulation experiments in which the same
veins were stimulated in the absence and presence of AVP, a paired
t test was used. Statistical significance was accepted at
P<.05.
Results
Top
Abstract
Introduction
Methods
Results
Discussion
References
Effects of AVP
AVP (10-9 to 10-6
mol/L) caused concentration-dependent contractions with an
EC50 of 1.5x10-8
mo/L, which is similar to values previously reported by
us.21 The presence of the
V1 antagonist
d(CH2)5Tyr(Me)AVP in the
organ bath displaced the control curve to AVP to the right in a
parallel manner (EC50,
2.8x10-7 mol/L), but differences in the maximal
tensions developed were not significant (23.1±3.3%, n=8, versus
23.3±3.8%, n=5, of response to 100 mmol/L KCl). The
1-adrenoceptor blocker prazosin
(10-6 mol/L) did not affect the
concentration-response curve to AVP (EC50,
1.1x10-8 mol/L; maximal response, 22.4±3.1%
of KCl contraction).
Electrical stimulation induced frequency-dependent increases in
tension in all the experiments that were abolished by tetrodotoxin
(10-6 mol/L) and prazosin
(10-6 mol/L), thus indicating that the effect
was due to the release of norepinephrine from perivascular
adrenergic nerves acting on
1-adrenoceptors. 
and 1B). The V1
receptor antagonist
d(CH2)5Tyr(Me)AVP
(10-6 mol/L) did not change control responses to
electrical field stimulation but prevented the amplifying effect of AVP
at all the frequencies used (Fig 1C).
View larger version (20K):
[in a new window]
Figure 1. A, Tracings of contractile responses to field
electrical stimulation (2 Hz) of isolated human saphenous veins under
control conditions and after incubation with various concentrations of
arginine vasopressin (AVP; 10-10 to 3x10-9
mol/L). B, Average contractions to electrical field stimulation in the
absence and in the presence of increasing concentrations of AVP
(10-10 to 3x10-9 mol/L). C, Effects of
3x10-9 mol/L AVP on frequency-dependent contractile
responses to electrical field stimulation in the absence and in the
presence of V1 receptor antagonist
d(CH2)5Tyr(Me)AVP (10-6 mol/L).
*Significant differences from control value,
P<.05. ).
View larger version (22K):
[in a new window]
Figure 2. A, Contractile response to electrical field
stimulation (2 Hz) in the absence and in the presence of increasing
concentrations of the V1 receptor agonist
[Phe,2 Orn8]-vasotocin (10-10 to
3x10-9 mol/L). The presence of the V1 receptor
antagonist d(CH2)5Tyr(Me)AVP
(10-6 mol/L) abolished the augmentation of the contraction
to electrical field stimulation by the V1 receptor agonist.
B, Contractile responses to electrical field stimulation in the absence
and in the presence of increasing concentrations of the V2
receptor antagonist [d(CH2)5,
D-Ile,2 Ile,4 Arg8]-vasopressin
(10-8 to 10-6 mol/L). The potentiation
induced by AVP (3x10-9 mol/L) was not affected in the
presence of the V2 receptor antagonist. C,
Frequency-response relationship in the absence and presence of cocaine
(10-6 mol/L) or cocaine together with AVP
(3x10-9 mol/L). Values are mean±SEM. *Significant
differences (P<.05) from control value. 
shows that the
potentiation induced by AVP was not modified in the presence of
10-8 to 10-6 mol/L of the
V2 receptor antagonist. In addition,
the selective V2 receptor agonist desmopressin
(10-9 to 10-7 mol/L) did
not modify the control frequency-response relationship
(P>.05, n=6) (results not shown). ).
AVP potentiated norepinephrine-induced contractions in
a concentration-dependent manner (Fig 3A). The norepinephrine
EC50 values and maximal responses in the presence
and absence of AVP are shown in the Table. The
V1 receptor antagonist
d(CH2)5Tyr(Me)AVP produced
a parallel, rightward shift of the potentiating effects of
3x10-9 mol/L AVP on the
norepinephrine concentration-response curve. At
10-6 mol/L, the V1
inhibitor brought the EC50 to values
similar to those obtained in the norepinephrine control
curve. In contrast, AVP (10-10 to
3x10-9 mol/L) did not affect the
concentration-response curve to KCl (10 to 120 mmol/L) (Fig 3B).
View larger version (15K):
[in a new window]
Figure 3. A, Contractile effects of
norepinephrine in the absence ( 
, n=6) and
in the presence of arginine vasopressin (AVP) (
, 10-9
mol/L, n=4; 
, 3x10-9 mol/L, n=4) and in the presence
of the V1 receptor antagonist
(10-6 mol/L) together with AVP (3x10-9
mol/L, 
, n=4). B, Concentration-response curves to KCl in the
absence (, n=9) and in the presence (
, n=7) of
3x10-9 mol/L AVP. Values are mean±SEM.
View this table:
[in a new window]
Table 1. EC50 Values and Maximal Contractions to
Norepinephrine Alone (Control) and in the Presence of
Either AVP or the V1 Receptor Antagonist
Together With AVP
The dihydropyridine calcium
antagonist nifedipine
(10-6 mol/L) did not significantly change the
contraction induced by AVP and electrical field stimulation (Fig 4A and 4B). The presence of
nifedipine diminished maximal responses to
norepinephrine, but EC50 was not
altered (6.6x10-7 versus
5.2x10-7 mol/L) (Fig 4C). In addition, the
enhancement of the contractile responses to electrical field
stimulation and norepinephrine by AVP was identical to that
observed in the absence of nifedipine (Fig 4B and 4C).
However, KCl-induced contractions were significantly reduced in the
presence of nifedipine (10-6 mol/L)
(Fig 4D).
View larger version (30K):
[in a new window]
Figure 4. A, Concentration-response curves to AVP in the
absence ( , n=7) and in the presence (, n=6) of
nifedipine (10-6 mol/L). B, Frequency-response
relationship under control conditions (solid bars, n=5) and in the
presence of nifedipine (10-6 mol/L, open bars,
n=5) or nifedipine plus AVP (3x10-9 mol/L,
hatched bars, n=5). C, Concentration-response curves to
norepinephrine in the absence (, n=6) and in the
presence of either nifedipine (10-6 mol/L,
, n=8) or nifedipine together with AVP
(3x10-9 mol/L, , n=6). D, Concentration-response
curves to KCl in the absence (, n=7) and in the presence of
nifedipine (10-6 mol/L, , n=7). Values are
mean±SEM. *Significant differences from control values,
P<.05.
Discussion
Top
Abstract
Introduction
Methods
Results
Discussion
References
The results of this study demonstrate that in the human saphenous
vein, low concentrations of AVP enhance the contractile effects of
electrical field stimulation and norepinephrine. The
potentiating effects occur at AVP concentrations substantially lower
than those required to produce a clear direct contractile response. In
a previous work,21 we found that contractions of
human saphenous veins in response to AVP are relatively low compared
with human arteries, indicating that these veins may have a low
population or sensitivity of receptor sites for this peptide. However,
an interesting finding of the present study is that the low
responsiveness of the saphenous vein coincides with a high sensitivity
to the modulating effects of AVP on adrenergic-mediated responses.
Thus, it appears that the indirect (potentiating) effects of AVP on
human saphenous vein may act synergistically with the effects of
adrenergic stimulation. 1-adrenoceptor
blocker, suggests that the action of this peptide does not involve
release of norepinephrine. The possibility that AVP could
block the reuptake of norepinephrine and therefore enhance
the contractile responses is unlikely because the potentiating effects
were still evident in the presence of cocaine. Alternatively,
AVP-induced potentiation could be due to alterations at the receptor
level, leading to an increased affinity of norepinephrine
for its receptor. This may be a likely explanation because AVP
increased the contractions to exogenously applied
norepinephrine. Thus, our data are consistent with
the suggestion that potentiation of the effects of nerve stimulation by
AVP corresponds to a postsynaptic enhancement of the action of
norepinephrine.
Acknowledgments
This work was supported by the Comisión Interministerial
de Ciencia y Tecnología, Ministerio de Sanidad, and
Generalitat Valenciana.
References
Top
Abstract
Introduction
Methods
Results
Discussion
References
1.
Michell RM, Kirk CJ, Billah MM. Hormonal
stimulation of phosphatidylinositol breakdown, with particular
reference to the hepatic effects of vasopressin. Biochem Soc
Trans. 1979;7:861–865.[Medline]
[Order article via Infotrieve]-adrenoceptor-mediated pressor responses by
NG-nitro-L-argnine methyl ester
and vasopressin in endotoxin-treated pithed rats. Eur J
Pharmacol. 1992;224:63–69.[Medline]
[Order article via Infotrieve]
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