Department of Pharmacology and Therapeutics, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada R3E 0W3
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ABSTRACT |
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The
involvement of nitric oxide (NO) in the vascular escape from
norepinephrine (NE)-induced vasoconstriction was investigated in the
hepatic arterial vasculature of anesthetized cats. The hepatic artery
was perfused by free blood flow or pump-controlled constant-flow, and
NE (0.15 and 0.3 µg · kg1 · min
1,
respectively) was infused through the portal vein. In the free-flow perfusion model, the NE-induced hepatic vasoconstriction recovered from
the maximum point of the constriction, resulting in 36.6 ± 5.9%
vascular escape. Blockade of NO formation with
N
-nitro-L-arginine methyl ester
(L-NAME, 2.5 mg/kg ipv) potentiated NE-induced maximum
vasoconstriction, and the potentiation was reversed by
L-arginine (75 mg/kg ipv). Furthermore, NE-induced vasoconstriction became more stable after L-NAME, resulting
in an inhibition of vascular escape (7.5 ± 3.3%), and the inhibition was reversed by L-arginine (23.0 ± 6.4%). Similar
potentiation of NE-induced vasoconstriction and inhibition of hepatic
vascular escape by L-NAME (40.4 ± 4.3% control vs. 10.2 ± 3.7% post-L-NAME escape) and the reversal by
L-arginine were also observed in the constant-flow
perfusion model. The data suggest that NO is the major endogenous
mediator involved in the hepatic vascular escape from NE-induced vasoconstriction.
liver; blood flow; N-nitro-L-arginine methyl ester; in
vivo
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INTRODUCTION |
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VASCULAR ESCAPE, characterized by the recovery of
initial decreased blood flow and vascular conductance toward the
control level during continued vasoconstrictive stimulation, is a
unique vascular defense mechanism, preventing tissue from insufficient blood supply during prolonged vasoconstrictive challenge
(7). The secondary vasodilation during vascular escape is
due to the relaxation of the smooth muscle of the same vessels that
were originally constricted (8). It has long been suggested that a
vasodilative substance(s) released after the vasoconstrictive stimuli
may be the primary mechanism responsible for the vascular escape. So
far, the possible involvement of endogenous vasodilators such as
adenosine, prostaglandins, histamine, -adrenergic agonist, and
acetylcholine has been tested and eliminated (reviewed in Refs. 7 and
13). Chen and Sheppherd (3) suggested that the reduced pH that occurred
during reduction of blood flow induced by norepinephrine (NE) resulted
in a selective inhibition of postjunctional
2-adrenergic
receptors in the canine intestine. However, hepatic venous pH was
unaltered at the point of full escape in response to sympathetic nerve
stimulation in the cat (10). The hypoxia induced by decreased blood
flow during vasoconstriction also does not appear to cause vascular
escape because a shift to anaerobic metabolism had no significant
influence on vascular escape in rat skeletal microvascular circulation
(23). Previous studies have shown an inhibitory effect of glucagon on
vascular escape in cat hepatic artery (HA) (4) and of insulin in rabbit
renal arterial circulation (6). However, the lack of a
demonstrated local stimulation-release cascade and the
supraphysiological doses required make it difficult to evaluate the
contribution of insulin and glucagon in physiological situations.
Nitric oxide (NO) is a powerful vasodilator endogenously released from vascular endothelium in response to many vasoconstrictive stimuli, including NE and sympathetic nerve stimulation, through both a direct receptor-operated mechanism (27) and induction by increased shear stress caused by vasoconstriction (9). Increasing evidence suggests that NO released during vasoconstriction attenuates the initial constriction and probably mediates the vascular escape. Blockade of NO formation with NO synthase inhibitor potentiated the vasoconstriction induced by NE or sympathetic nerve stimulation (17, 19-21). In contrast, NO donors or endogenous activation of NO synthase inhibited NE-induced vasoconstriction (18, 28). Methylene blue, an inhibitor of guanylate cyclase, which is the key enzyme in NO-induced vasodilatation, diminished vascular escape during NE infusion in rat mesenteric artery (24).
The purpose of the present study was to test the hypothesis that NO is the major mediator for the induction of vascular escape in the HA. The HA vascular escape from NE-induced vasoconstriction was compared before and after inhibition of NO formation in both free-flow and pump-controlled constant-flow perfusion of the HA. The results suggest that blockade of NO formation inhibited vascular escape and that this inhibition could be reversed by reactivation of NO synthase with L-arginine in cat HA.
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MATERIALS AND METHODS |
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Surgical Preparation
Free-flow infusion of HA and portal vein. The surgery and instrumentation were previously described (11). Briefly, cats of either sex (n = 9, 3.6 ± 0.1 kg body wt) were fasted overnight and anesthetized with pentobarbital sodium (32.5 mg/kg) via an intraperitoneal injection. Anesthesia was maintained using a continuous intravenous infusion (0.78 mg/ml saline) adjusted as required via a brachial vein cannula. Body temperature was maintained at 37.5 ± 0.5°C by means of a rectal probe and a thermal control unit that regulated heating rods in the surgical table. The animals were mechanically ventilated through an endotracheal tube with room air from a positive-pressure respirator (Harvard Apparatus, Millis, MA), and ventilation rate was adjusted by monitoring the changes in blood gas using a blood gas analyzer (System 1302; Instrumentation Laboratory, Lexington, MA).
Systemic arterial blood pressure (AP) was monitored from a catheter in the right carotid artery. Central venous pressure (CVP) was monitored from a cannula inserted via the right femoral vein into the inferior vena cava. The abdomen was exposed by a midline laparotomy, and the spleen was removed. The gastroduodenal artery and the inferior mesenteric artery were exposed and ligated. The periarterial nerve bundles around the superior mesenteric artery (SMA) and the HA were gently separated and cut to prevent any reflex influences. The celiac artery was isolated, and all of its branches were ligated except the common HA. This methodology ensures that all blood flow through the HA is from the celiac artery and that all of the portal blood flow is from the SMA, as previously described (14). Two electromagnetic flow probes (EP408 and EP406; Carolina Medical Electronics, King, NC) were placed around the SMA and celiac artery, respectively, for the measurement of SMA and HA blood flow (SMABF and HABF), and at the conclusion of the experiment the flow probes were calibrated in situ. Two intravenous catheters (24G OPTIVA; Johnson & Johnson Medical, Arlington, TX) were inserted into the portal vein for drug delivery and portal venous pressure (PVP) measurement.Pump-served controlled-flow model for the infusion of HA and portal vein. To avoid simultaneous changes of blood pressure and flow during NE infusion, an in situ perfusion model that allows only blood pressure to change but keeps the flow constant was established in another seven cats (3.7 ± 0.1 kg body wt). The general surgical preparation was similar to the free-flow infusion model described above. In addition, a vascular bypass was introduced by double cannulation into the abdominal aorta below the level of the renal arteries to permit blood to be withdrawn from the bypass while maintaining aortic flow below the bypass. Two pump-controlled (Masterflex; Cole Parmer Instrument, Barrington, IL) vascular circuits were then set up to drive the outflow of the blood from the bypass into both the SMA and HA. The infusion blood pressure was adjusted similarly to the AP. Two flow-through electromagnetic flow probes (EP608; Carolina Medical Electronics) and two catheters were incorporated into the circuits to measure the blood flow rate and the infusion pressures, respectively.
In both models, the AP, HAP, PVP, and CVP were monitored with Gould Statham pressure transducers and were recorded on a polygraph recorder (R611; Sensor Medics Dynograph, Anaheim, CA). The transducers were set to zero reference level relative to the midpoint of the inferior vena cava at the hepatic outlet. The animals were heparinized with 200 U/kg heparin.Protocols
Free-flow model.
The cats (n = 9) were allowed to stabilize after surgery for at
least 1 h until stable basal hemodynamics were achieved. Then the
animals were prechallenged twice with intraportal infusion of
NE (0.15 µg · kg1 · min
1
for 3 min) to ensure the stabilization of the HA response to NE
thereafter. Preliminary experiments in four cats showed that the AP,
PVP, and HABF responses were stable in the following six challenges of
NE. Then the following protocols were tested.
Hepatic arterial vascular escape from NE stimulation.
Intraportal infusion of NE (n = 9; 0.15 µg · kg1 · min
1
for 3 min) was performed to initiate HA vasoconstriction, and the
vascular escape was measured. The dose of NE was chosen to achieve an
adequate vasoconstriction in the HA vasculature without significant
influence on portal venous blood flow, to rule out the potential impact of the change in portal venous blood flow on the reactivity of the HA
due to the HA buffer response (12). Only one dose of NE was used
because previous studies had shown that the HA escape during NE
stimulation is dose independent in the dose range from 0.125-1.25
µg · kg
1 · min
1
(4).
Blockade of NO formation on vascular escape.
In the same group of animals, endogenous NO formation was blocked with
N-nitro-L-arginine methyl ester
(L-NAME, 2.5 mg/kg iv). Fifteen minutes later, when
steady-state basal hemodynamics were achieved, intraportal infusion of
NE was repeated.
Reversal effect of L-arginine. In eight of nine cats in this group, an intravenous bolus injection of 75 mg/kg L-arginine was administered to restore the activity of NO synthase after L-NAME. NE infusion was repeated 10 min thereafter.
Pump-served constant-flow model.
All of the above protocols were performed in the pump-controlled
constant-flow condition in another group of seven cats. For this group,
the dose of NE was 0.3 µg · kg1 · min
1.
The high dose of NE in the constant-flow model could be used because
NE-induced changes in portal flow were prevented by use of the
perfusion circuit.
Calculations
Hemodynamic variables were determined before NE infusion (control) at maximum vasoconstriction during NE infusion judged from the minimal HA flow level or, in the pump-controlled constant-flow model, from the maximum hepatic arterial pressure (HAP) attained (peak response ~30 s after starting NE infusion) and at the end of a 3-min infusion period (plateau). Hepatic arterial conductance (HAC) was calculated as the ratio of HABF to (HAPAll data are expressed as means ± SE. A one-way ANOVA followed by Tukey's test was employed when the multiple means from different groups were compared. The paired t-test was employed when two means within the group were compared. In appropriate conditions, an unpaired Student's t-test was applied. P < 0.05 was selected for acceptance of statistical significance.
All chemicals were purchased from Sigma (St. Louis, MO) and were freshly prepared daily. NE, L-NAME, and L-arginine were dissolved in saline. The experimental procedures were approved by the Ethics Committee on Animal Care at the University of Manitoba and performed in accordance with The Guide to the Care and Use of Experimental Animals, Canadian Council on Animal Care.
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RESULTS |
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Free-Flow Model
General hemodynamics.
Baseline hemodynamics in control, after L-NAME, and after
L-arginine are reported in Table
1. L-NAME increased baseline AP and decreased SMAC but had no significant influence on other
hemodynamics. The changes in baseline AP and SMAC caused by
L-NAME were reversed by L-arginine.
Furthermore, L-NAME potentiated NE-induced vasoconstriction in both systemic and portal venous circulation, as demonstrated by the
greater increases in both AP and PVP, and the potentiated effects of
L-NAME were reversed by L-arginine (Fig.
1). Intraportal infusion of NE did not
alter SMABF in any of the conditions tested. The data indicate an
adequate blockade of NO formation by L-NAME and the
efficiency of L-arginine to reverse the formation of NO in
hepatic circulation in our model.
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Hepatic arterial vascular escape from NE stimulation.
Intraportal infusion of NE induced an intense initial HA
vasoconstriction, which reached a maximum ~30 s after the start of NE
infusion (Fig. 2). The maximum
vasoconstriction resulted in a 26.0 ± 5.7% decrease in HABF and a
40.9 ± 5.0% decrease in HAC. Thereafter, the HABF and HAC underwent
a partial return toward baseline despite continued NE infusion and
reached a plateau within 3 min (vascular escape). The calculated flow
escape was 92.8 ± 16.8%, and the conductance escape was 36.6 ± 5.9%, as shown in Fig. 2.
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Blockade of NO formation on vascular escape.
Administration of L-NAME had no significant influence on
basal HA vascular tone but enhanced NE-induced HA vasoconstriction. The
HABF decreased by 7.5 ± 1.2 ml · min1 · kg
1,
and HAC decreased by 0.097 ± 0.018 ml · min
1 · kg
1 · mmHg
1
at the point of maximum constriction, resulting in a 40.0 ± 4.2% decrease in HABF and a 52 ± 3.7% decrease in HAC (both P < 0.05). However, vascular escape was inhibited by L-NAME.
The return of HABF at the end of the NE infusion only reached 12.2 ± 1.4 ml · min
1 · kg
1,
and HAC only reached 0.092 ± 0.018 ml · min
1 · kg
1 · mmHg
1,
representing a significant decrease both in flow escape (22.1 ± 11.8%) and conductance escape (7.5 ± 3.3%) compared with before L-NAME (both P < 0.001), as reported in Figs.
3 and 4. The data suggested
that a NO component was involved in counteracting NE-induced hepatic
vasoconstriction and resulted in vascular escape
thereafter.
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Reversal effect of L-arginine. To further confirm that the inhibitory effect of L-NAME on hepatic vascular escape was due to the inhibition of NO formation, L-arginine, a NO synthesis precursor, was used after L-NAME to reverse the inhibition of NO synthase. Administration of L-arginine had no significant influence on basal HABF or HAC but partially reversed the potentiating effect of L-NAME on NE-induced vasoconstriction of the HA (Fig. 4). Furthermore, L-arginine reversed the inhibitory effect of L-NAME on hepatic vascular escape after NE stimulation, as reported in Figs. 3 and 4.
Constant-Flow Model
Overall, comparisons of baseline HAP, PVP, HABF, and SMABF revealed no significant differences between the control after L-NAME and after L-arginine, as shown in Table 2. Intraportal infusion of NE increased HAP by 44.4 ± 7.2 from 88.9 ± 3.5 mmHg at the initial maximum point of constriction and by 27.1 ± 5.6 mmHg at the plateau, resulting in 40.4 ± 4.3% vascular escape. After L-NAME, NE-induced HAP increased to 78.6 ± 12.4 mmHg at the maximum point and remained at 72.7 ± 13.1 mmHg at the plateau, representing a significant inhibition of vascular escape (10.2 ± 3.7%) compared with before L-NAME. In five of seven cats in this group, L-arginine was used after L-NAME. L-Arginine totally reversed the potentiated effect on HA vasoconstriction and the inhibitory effect on vascular escape by L-NAME, as reported in Figs. 5 and 6.
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DISCUSSION |
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The purpose of the present study was to investigate the hypothesis that endogenous NO regulates vascular escape during sustained NE infusion in cat HA vasculature. This hypothesis was tested by examining the effects of blockade of NO formation with L-NAME on the responses of prolonged NE infusion in two different in situ perfusion situations: free-flow and constant-flow perfusion of the HA. The main finding is that NO endogenously released after NE stimulation appears to be the major mediator responsible for inducing HA vascular escape from NE-induced vasoconstriction. Blockade of NO formation with L-NAME significantly inhibited vascular escape, and this inhibition was reversed by reactivation of NO synthase with L-arginine. To our knowledge, this is the first in vivo study performed in the HA vasculature showing endogenous NO as a major mediator in inducing vascular escape.
Methodological Considerations
The free-flow perfusion model is more physiological than the constant-flow model. However, three limitations exist with the free-flow preparation in assessing hepatic vascular escape: 1) The potential change in SMABF during NE infusion will impact the responsiveness of the HA to NE due to the HA buffer response, and this mechanism accounts for the observation that a change in portal flow leads to a rapid and opposite change in HA flow so that total hepatic flow tends to be maintained constant (14); 2) the administration of NE changes AP and HABF simultaneously, and this makes it difficult to determine the true maximal point of vasoconstriction, which is essential in analyzing the vascular escape response; and 3) HA blood pressure is estimated from AP. To avoid these limitations, we also performed the experiments in an in situ perfusion model that allowed only HA blood pressure to increase and at the same time held the HABF and portal flow constant during NE infusion. The responses of systemic and hepatic vascular beds to NE, L-NAME, or L-arginine are similar in these two models, indicating that both models are reliable in assessing hepatic hemodynamics.Ideally, the same approach would be tested in the constant-flow condition in which shear stress is allowed to rise and in the constant-pressure situation in which the change in shear stress is avoided (17). We did not perform this test because of technical limitations. Even though the HA blood pressure may be held steady to avoid the increase in HA shear stress induced by vasoconstriction, the portal system also responds to constriction by elevated shear stress and NO release (16), so that both circuits would have to be precisely and rapidly controlled to avoid shear effects during the peak constriction and the escape. In this event, the required decrease in portal flow would have a dilation effect on the HA through the HA buffer response. Because of these limitations, we cannot answer whether the NO released during the vasoconstriction and leading to the escape is agonist dependent (1, 25) or shear stress dependent (2, 5, 9) or whether the site of NO release is from the HA or the portal vessels.
The dose of L-NAME or L-arginine used in the present study has previously been demonstrated to achieve an adequate blockade of NO formation or reactivation of NO synthase after L-NAME in hepatic circulation (17). The effectiveness of the drugs was verified in the present study, as indicated by the significant elevation in baseline AP and the more apparent increment of HAP and PVP following NE infusion after L-NAME and the reversal of these effects by L-arginine.
Hepatic Vascular Escape
The vascular escape from sympathetic nerve stimulation- and NE infusion-induced vasoconstriction is well established as a genuine physiological phenomenon in cat HA in vivo and in vitro (7). Greenway et al. (8) observed that the vascular escape in the cat mesenteric vascular bed was not related to blood flow redistribution and concluded that the vasodilation during the vascular escape involves mainly the relaxation of the same vessels that originally constricted. The lack of flow redistribution has been further supported in the HA by the measurement of microsphere distribution as well as oxygen consumption (10) and lidocaine clearance (16). The present study demonstrates that NO is the major endogenous vasodilator involved in inducing the hepatic vascular escape from NE stimulation.Our findings are consistent with other reports that suggest the involvement of NO in vascular escape. In rat systemic circulation, the vascular escape from angiotensin II-induced constriction was inhibited by NO synthase blockade, and L-arginine reversed this inhibition (26). In rat SMA, Remak et al. (24) observed that vascular escape from NE was inhibited by the inhibition of NO action with methylene blue. Interestingly, NO is also the major mediator involved in the vascular escape of hepatic portal circulation; blockade of NO formation significantly inhibited the portal venous vascular escape from ethanol-induced vasoconstriction in rat liver (22).
In conclusion, although NO was not involved in control of basal HA tone, the continuous release of NO during adrenergic stimulation plays an important role in modulating vascular tone in cat HA vasculature. In addition to preventing extreme constriction of arterial vessels by limiting maximum adrenergic vasoconstriction, the direct vasodilative effect of NO and its modulation of adrenergic vasoconstriction regulate the vascular tone during adrenergic stimulation toward the prestimulation level and cause the HA escape. This regulatory effect of NO is important in maintaining the blood supply to the liver in conditions of high adrenergic stress. In the liver, the blood from the HA is the main source of oxygen supply and the adequacy of blood supply is essential for maintaining hepatic metabolic function (15).
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ACKNOWLEDGEMENTS |
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We thank Dallas Legare for excellent technical support.
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FOOTNOTES |
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This study was supported by operating grants from the Medical Research Council of Canada and the Heart and Stroke Foundation of Manitoba. Z. Ming is the recipient of a Manitoba Health Research Council Fellowship Award.
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. §1734 solely to indicate this fact.
Address for reprint requests and other correspondence: W. W. Lautt, Dept. of Pharmacology and Theraputics, Faculty of Medicine, Univ. of Manitoba, Winnipeg, MB, Canada R3E 0W3.
Received 12 April 1999; accepted in final form 18 August 1999.
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REFERENCES |
---|
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---|
1.
Bockman, C. S.,
W. B. Jefferies,
and
P. W. Abel.
2-Adrenoceptor subtype causing nitric oxide-mediated vascular relaxation in rats.
J. Pharmacol. Exp. Ther.
278:
1235-1243,
1996[Abstract].
2.
Busse, R.,
and
I. Fleming.
Pulsatile stretch and shear stress: physical stimuli determining the production of endothelium-derived relaxing factors.
J. Vasc. Res.
35:
73-84,
1998[Medline].
3.
Chen, L. Q.,
and
A. P. Sheppherd.
Role of H+ and 2-receptors in escape from sympathetic vasoconstriction.
Am. J. Physiol.
261 (Heart Circ. Physiol. 30):
H868-H873,
1991
4.
D'Almeida, M. S.,
and
W. W. Lautt.
The effect of glucagon on vasoconstriction and vascular escape from nerve- and norepinephrine-induced constriction of the hepatic artery of the cat.
Can. J. Physiol. Pharmacol
67:
1418-1425,
1989[Medline].
5.
Fleming, I.,
J. Bauersachs,
B. Fisslthaler,
and
R. Busse.
Ca2+-independent activation of the endothelial nitric oxide synthase in response to tyrosine phosphatase inhibitors and fluid shear stress.
Circ. Res.
82:
686-695,
1998
6.
Forti, A. C.,
and
M. C. Fonteles.
Effect of insulin on renal vascular escape in normal and diabetic kidney.
Horm. Metab. Res.
27:
6-9,
1995[Medline].
7.
Greenway, C. V.
Autoregulatory escape in arteriolar resistance vessels.
In: Smooth Muscle Contraction, edited by N. L. Stephens. New York: Marcel Dekker, 1984, p. 473-484.
8.
Greenway, C. V.,
G. D. Scott,
and
J. Zink.
Sites of autoregulatory escape of blood flow in the mesenteric vascular bed.
J. Physiol. (Lond.)
259:
1-12,
1976[Medline].
9.
Hecker, M.,
A. Mulsch,
E. Bassenge,
and
R. Busse.
Vasoconstriction and increased flow: two principal mechanisms of shear stress-dependent endothelial autacoid release.
Am. J. Physiol.
265 (Heart Circ. Physiol. 34):
H828-H833,
1993
10.
Lautt, W. W.
Effect of stimulation of hepatic nerves on hepatic O2 uptake and blood flow.
Am. J. Physiol.
232 (Heart Circ. Physiol. 1):
H652-H656,
1977[Medline].
11.
Lautt, W. W.
Carotid sinus baroreceptor effects on cat livers in control and hemorrhaged states.
Can. J. Physiol. Pharmacol.
60:
1592-1602,
1982[Medline].
12.
Lautt, W. W.
Mechanism and role of intrinsic regulation of hepatic arterial blood flow: hepatic arterial buffer response.
Am. J. Physiol.
249 (Gastrointest. Liver Physiol. 12):
G549-G556,
1985[Medline].
13.
Lautt, W. W.
Hepatic circulation.
In: Nervous Control of Blood Vessels, edited by T. Bennett,
and S. M. Gardiner. Amsterdam, The Netherlands: Harwood Academic, 1996, p. 465-503.
14.
Lautt, W. W.,
D. J. Legare,
and
M. S. d'Almeida.
Adenosine as putative regulator of hepatic arterial flow (the buffer response).
Am. J. Physiol.
248 (Heart Circ. Physiol. 17):
H331-H338,
1985[Medline].
15.
Lautt, W. W.,
and
M. P. Macedo.
Hepatic circulation and toxicology.
Drug Metab. Rev.
29:
369-395,
1997[Medline].
16.
Lautt, W. W.,
and
F. S. Skelton.
Effect of hepatic nerve stimulation on hepatic uptake of lidocaine in the cat.
Life Sci.
19:
433-436,
1976[Medline].
17.
Macedo, M. P.,
and
W. W. Lautt.
Shear-induced modulation of vasoconstriction in the hepatic artery and portal vein by nitric oxide.
Am. J. Physiol.
274 (Gastrointest. Liver Physiol. 37):
G253-G260,
1998
18.
Miura, H.,
A. Gardemann,
J. Rosa,
and
K. Jungermann.
Inhibition by noradrenaline and adrenaline of the increase in glucose and lactate output and decrease in flow after sympathetic nerve stimulation in perfused rat liver: possible involvement of protein kinase C.
Hepatology
15:
477-484,
1992[Medline].
19.
Nase, G. P.,
and
M. A. Boegehold.
Endothelium-derived nitric oxide limits sympathetic neurogenic constriction in intestinal microcirculation.
Am. J. Physiol.
273 (Heart Circ. Physiol. 42):
H426-H433,
1997
20.
Nase, G. P.,
and
M. A. Boegehold.
Modulation of sympathetic constriction by the arteriolar endothelium does not involve the cyclooxygenase pathway.
Int. J. Microcirc.
17:
41-47,
1997[Medline].
21.
Nase, G. P.,
and
M. A. Boegehold.
Postjunctional 2-adrenoceptors are not present in proximal arterioles of the rat intestine.
Am. J. Physiol.
274 (Heart Circ. Physiol. 43):
H202-H208,
1998
22.
Oshita, M.,
Y. Takei,
S. Kawano,
H. Yoshihara,
T. Hijioka,
H. Fukui,
M. Goto,
E. Masuda,
Y. Nishimura,
H. Fusamoto,
and
T. Kamada.
Roles of endothelin-1 and nitric oxide in the mechanism for ethanol-induced vasoconstriction in rat liver.
J. Clin. Invest.
91:
1337-1342,
1993[Medline].
23.
Pal, M.,
A. Toth,
P. P. Ping,
and
P. C. Johnson.
Capillary blood flow and tissue metabolism in skeletal muscle during sympathetic trunk stimulation.
Am. J. Physiol.
274 (Heart Circ. Physiol. 43):
H430-H440,
1998
24.
Remak, G.,
O. D. Hottenstein,
and
E. D. Jacobson.
Adrenergic, purinergic, and endothelial mediators and modulators of norepinephrine-induced mesenteric autoregulatory escape.
Dig. Dis. Sci.
39:
1655-1664,
1994[Medline].
25.
Ruffolo, R. R.,
and
J. P. Hieble.
-Adrenoceptors.
J. Pharmacol. Ther.
61:
1-64,
1994.
26.
Shebeko, V. I.,
and
I. Rodionov.
NO-synthase inhibition induces a resistant pressor reaction during the 10-minute intravenous infusion of angiotensin-2 to narcotized rats (Abstract).
Biull. Eksp. Biol. Med.
116:
479,
1993[Medline].
27.
Tschudi, M.,
V. Richard,
F. R. Buhler,
and
T. F. Luscher.
Importance of endothelium-derived nitric oxide in porcine coronary resistance arteries.
Am. J. Physiol.
260 (Heart Circ. Physiol. 29):
H13-H20,
1991
28.
Weidenbach, H.,
A. K. Nussler,
Z. Shu,
G. Adler,
and
K. Beckh.
Nitric oxide formation lowers norepinephrine-induced intrahepatic resistance without major effects on the metabolism in the perfused rat liver.
Hepatology
26:
147-154,
1997[Medline].