| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
1 Department of Cardiovascular Medicine, University of Tokyo Graduate School of Medicine, Bunkyo-ku, Tokyo 113-8655; and 2 Department of Pathology, Tokai University School of Medicine, Kanagawa 259-1193, Japan
 |
ABSTRACT |
|---|
 TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
Heme oxygenase (HO) is a
heme-catabolizing enzyme that converts heme into biliverdin, iron, and
carbon monoxide. HO-1, an inducible form of HO, is thought to act as an
endogenous antioxidant defense mechanism. To determine whether chronic
administration of angiotensin II affects HO-1 expression in the heart,
expression and localization of HO-1 were investigated in the heart of
rats receiving angiotensin II infusion (0.7 mg · kg
1 · day1) via osmotic minipump for
up to 7 days. Angiotensin II induced formation of granulation tissue,
characterized by myofibroblast proliferation, fibrous deposition, and
inflammatory cell migration. Angiotensin II also upregulated cardiac
HO-1 expression. Immunohistochemistry revealed that HO-1 was
intensively expressed in the granulation tissue. The selective
AT1-receptor antagonist, losartan, completely, but
hydralazine only partially, suppressed angiotensin II-induced granulation tissue formation and HO-1 upregulation. Chronic
norepinephrine infusion (2.8 mg · kg1 · day1) did not induce granulation tissue formation or HO-1
upregulation. Our data suggest that angiotensin II upregulates cardiac
HO-1 expression in the newly formed inflammatory lesion, which may represent an adaptive response to angiotensin II-induced cardiac damage.
norepinephrine; blood pressure; immunohistochemistry; oxidative stress
| |
INTRODUCTION |
|---|
|
TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
HEME OXYGENASE (HO) is a heme-catabolizing enzyme that converts heme into biliverdin, iron, and carbon monoxide. HO has two isoforms: HO-1, an inducible form, and HO-2, a constitutive form. HO-1 expression is increased by various oxidative insults (6, 9, 32). Induced HO-1 is thought to act as an antioxidant defense mechanism through degrading cellular heme (prooxidant) and increasing biliverdin (antioxidant) (29). HO-1 may also play a role in suppressing an acute complement-dependent inflammatory response (34). The recent findings that cultured fibroblasts from HO-1-deficient mice were hypersensitive to cytotoxicity caused by hydrogen peroxide (23) and that transformed lymphoblastoid cells derived from a human case of HO-1 deficiency was extremely sensitive to hemin-induced cell injury (35) provide further evidence that HO-1 acts favorably against oxidant-induced cellular injury.
The produced carbon monoxide has been hypothesized to serve a physiological role in regulating vascular tone (4), which is mediated by a cGMP-signaling pathway and by calcium-activated potassium channels (33). The HO system is also present and regulated in the heart (12, 20, 22, 25). The cardiac HO system may have a role in preventing arteriosclerosis (7), improving cardiac xenograft survival (28), regulating blood pressure (20), and modulating nitric oxide-mediated myocardial preservation (17). The recent finding that hypoxia induced severe right ventricular dilatation in HO-1 null mice also indicated the cardioprotective role of HO-1 in the stressed condition (36).
Using hypertensive rat model with chronic ANG II infusion, Ishizaka et al. (10) reported that pressure overload upregulated aortic HO-1 protein expression and activity. Through its antioxidant and anti-inflammatory properties, increased aortic HO-1 may act favorably against the tissue damage elicited by ANG II and pressure overload. It has been shown that the activated renin-angiotensin system and/or elevation of blood pressure participate in the initial signaling, which may mobilize inflammatory cells in the heart (21). We hypothesized that continuous infusion of ANG II may upregulate cardiac HO-1 expression, which may have a role in modulating the extent of cardiac injury mediated by increased circulating ANG II and/or hypertension. Therefore, the purpose of this study was to investigate whether or not HO-1 is regulated in the heart of hypertensive rats receiving ANG II infusion. To delineate the specific effects of ANG II and the elevation of blood pressure, we also made hypertensive rat model with chronic norepinephrine (NE) infusion. Here we report that HO-1 is upregulated in the heart of ANG II-induced hypertensive rats. Immunohistochemistry revealed that marked HO-1 expression was seen in the myofibroblasts and migrated inflammatory cells in the heart of rats with ANG II infusion.
| |
MATERIALS AND METHODS |
|---|
|
TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
Animal models.
To prepare the rat hypertension model, an osmotic minipump (Alzet
model 2001; Alza Pharmaceutical, Palo Alto, CA) was implanted into each
male Sprague-Dawley rat as described previously (11). ANG
II (Sigma, St. Louis, MO) was infused at the rate of 0.7 mg · kg1 · day1, unless otherwise
described. Systolic and diastolic blood pressures and heart rate were
measured in conscious rats by tail-cuff plethysmography (UR-5000; Ueda,
Tokyo, Japan). In some experiments, the selective AT1-receptor antagonist, losartan (a kind gift from R. D. Smith, DuPont/Merck; 25 mg · kg1 · day1), or the nonspecific vasodilator, hydralazine (15 mg · kg1 · day1; Sigma), was
given in the drinking water, beginning 2 days before pump implantation
and during ANG II infusion. To examine the effect of the subpressor
dose of ANG II, 0.25 mg · kg1 · day1 ANG II was infused. To examine another model of
hypertension, NE (Sigma) was infused at the rate of 2.8 mg · kg1 · day1 using the same minipump
system through a catheter that was placed in the superior vena cava via
the left external jugular vein (10).
RNA isolation and Northern blot analysis.
Total RNA was isolated from the homogenized heart by the acid
guanidinium thiocyanate-phenol chloroform method using Isogen (WAKO,
Osaka, Japan). Equal amounts of total RNA (15-20 µg) were subjected to electrophoresis in a 1.0% agarose gel containing 6.5%
formaldehyde. RNA was covalently bonded to the membranes with
ultraviolet crosslinking (UV Stratalinker 1800; Stratagene Cloning
Systems, La Jolla, CA). Rat HO-1 cDNA (a kind gift from Dr. S. Shibahara, Tohoku University School of Medicine, Japan) was labeled
with [
-32P]dCTP (NEN Research Products, DuPont,
Boston, MA) using a commercial kit (Nippon Gene, Tokyo, Japan). After
the membranes were prehybridized at 42°C for 2-5 h, the
hybridization reaction was performed overnight at 42°C. Membranes
were washed in 1× sodium chloride-sodium citrate and 0.1% SDS for 10 min at 50°C and twice for 10 min at 60°C. Hybridized bands
were visualized and quantified using the Bio-Imaging Analyzer, BAS 2000 (Fuji Photo Film, Tokyo, Japan).
Protein purification and Western blot analysis. Protein was isolated by homogenizing samples in the lysis buffer (in mmol/l: 50 HEPES, 5 EDTA, and 50 NaCl; pH 7.5) containing protease inhibitors (10 µg/ml aprotinin, 1 mmol/l PMSF, and 10 µg/ml leupeptin). Equal amounts of protein were loaded onto 15% SDS polyacrylamide gels and subsequently blotted onto the polyvinylidine difluoride membranes Immobilon-P (Millipore, New Bedford, MA). Antibodies against rat HO-1 and rat HO-2 (StressGen, Victoria, BC, Canada) were used at a 1:1,000 dilution, and horseradish conjugated secondary antibody (Jackson ImmunoResearch, West Grove, PA) was used at a 1:2,000 dilution. The ECL Western blotting system (Amersham, Arlington Heights, IL) was used for detection. Bands were visualized using lumino-analyzer (LAS-1000, Fuji Photo Film). Band intensity was calculated using the image analysis software, NIH Image (NIH, Research Service Branch), and it was expressed as a percent control.
Immunohistochemistry.
Immunohistochemistry was performed as described previously
(1). Briefly, after deparaffinization and rehydration,
sections were pretreated with 0.3% hydrogen peroxide in 70% methanol
to exhaust endogenous peroxidase activities. After the preincubation with 10% horse serum, the slides were incubated with the antibodies against rat macrophage/monocyte (ED1; Chemicon International, Temecula,
CA), rat HO-1 (StressGen), and human -smooth muscle actin (-SM
actin, Sigma) at 1/200, 1/200, and 1/1,000 dilutions, respectively. The
slides were then washed and incubated with biotinylated secondary
antibodies. After treatment of the slides with the avidine-biotinilated HRP complex (Vector Laboratories, Burlingame CA), the antigens were
visualized with the 3,3-diaminobenzidine tetrahydrochloride (Dako,
Carpenteria, CA) system. Counterstaining was performed with methyl
green (Dako). For semiquantification of the granulation tissue (areas
of fibrosis, myocardial necrosis, and myofibroblast proliferation), the
Masson's trichrome-stained heart sections were scanned using a
photoimaging system (Canon, Tokyo, Japan). The ratio of the
inflammatory areas (granulation/fibrosis) to the total myocardium area
was calculated using the image analysis software (NIH). Scattered areas
of the inflammatory area were not included in this calculation, and
thus, this method may have underestimated the true inflammatory areas.
Assay of HO activity. Hearts were homogenized in 250 mmol/l sucrose containing 50 mmol/l Tris · HCl (pH 7.5), and homogenates were centrifuged at 18,800 g at 4°C for 10 min. The supernatant was removed and recentrifuged at 100,000 g at 4°C for 60 min, and the precipitated microsomal fraction was suspended in 100 mmol/l potassium phosphate buffer (pH 7.4). Biliverdin reductase was crudely purified by the method of Tenhunen et al. (31). Heme oxygenase activity was assayed according to the method of Yoshida et al. (37).
Statistical analysis. Data are expressed as means ± SE. ANOVA followed by a multiple comparison test was used for comparisons of initial data before being expressed as a percentage of the control using the statistical analysis software Statistica ver. 5.1J for Windows (StatSoft, Tulsa, OK). A value of P < 0.05 was considered to be statistically significant.
| |
RESULTS |
|---|
|
TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
Effect of ANG II, NE, and inhibitors on systolic blood pressure.
Both ANG II and NE caused a significant raise in the blood pressure
(Fig. 1A) and in the heart
rates (Fig. 1B) by day 1, and the increase
continued through day 7. Blood pressure and heart rate at
day 1 were slightly higher in the NE-infused rats than in
the ANG II-infused rats; however, the differences were not statistically significant. Both the nonspecific vasodilator,
hydralazine, and the specific AT1-receptor inhibitor,
losartan, effectively normalized ANG II-induced hypertension at
day 7 (Fig. 1C). Treatment with either
hydralazine alone or losartan alone had no significant effect on blood
pressure or heart rate (data not shown).
|
Effect of ANG II infusion on HO-1 expression in the heart.
HO-1 mRNA was significantly increased as early as 3 days after ANG
II infusion and was increased further for up to 7 days (Fig.
2). This increase in HO-1 mRNA expression
was accompanied by an increase in HO-1 protein (Fig.
3, A and C),
whereas HO-2, the constitutive form of HO, was unchanged at 7 days
after ANG II infusion (Fig. 3B). HO activity in the
microsomal fractions was elevated in the heart of rats that received
ANG II infusion for 7 days compared with the sham-operated control
(control vs. ANG II: 3.2 ± 0.6 vs. 5.2 ± 0.4 bilirubin
generation · mg protein1 · h1, n = 5, respectively,
P < 0.01).
|
|
Effect of antihypertensive drugs, subpressor dose of ANG II, and
NE.
Losartan completely blocked the ANG II-induced HO-1 protein
upregulation (Fig. 4, B and
D), which indicated that ANG II-induced HO-1 upregulation
was an AT1 receptor-specific event. In contrast, hydralazine only partially suppressed the ANG II-induced HO-1 protein
upregulation (Fig. 4, A and C). These data
suggested that ANG II could upregulate cardiac HO-1 via its
pressor-independent effect. The finding that subpressor dose of ANG II
infusion resulted in a small but significant upregulation of HO-1
protein (Fig. 5, A and
C) further supported this notion. In contrast, NE did not
upregulate HO-1 protein expression (Fig. 5, B and D), which suggested that increase of circulating ANG II played a pivotal role in
HO-1 upregulation.
|
|
Histology and immunohistochemistry of the heart.
Masson's trichrome staining revealed that ANG II infusion induced a
right ventricle-dominant granulation tissue formation, which was
characterized by the proliferation of myofibroblasts, migration of
inflammatory cells, and fibrotic scar (Fig.
6A). Losartan completely
inhibited ANG II-induced inflammatory changes; however, hydrazine only
partially inhibited these changes. Subpressor dose of ANG II induced
similar inflammatory changes, though to a lesser extent. In contrast,
irrespective of marked elevation of the blood pressure, these
inflammatory changes were not seen in the heart of NE-infused rats
(Fig. 6B). Immunohistochemistry showed that spindle-shaped,
fibroblast-like cells in the granulation tissue were -SM actin
positive, and therefore, were identified to be myofibroblasts (Fig.
7B). These spindle-shaped
myofibroblasts were strongly positive for HO-1 staining, and some
cardiomyocytes surrounding the granulation tissue were also positive
for HO-1 staining (arrowheads in Fig. 7C). HO-1 was also
induced in scattered monocytes/macrophages in these areas (Fig.
7D).
|
|
| |
DISCUSSION |
|---|
|
TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
This study demonstrated that chronic infusion of ANG II, but not NE, upregulated HO-1 expression in the heart. The finding that hydralazine only partially blocked ANG II-induced HO-1 upregulation suggested that ANG II increased cardiac HO-1 expression in a pressor-independent manner, and that this response was augmented by pressor-effect of ANG II. Histological analysis showed the formation of granulation tissue, presenting as myofibroblast proliferation, fibrous deposit, and migration of monocytes/macrophages, in the heart of rats with ANG II infusion. Intense expression of HO-1 in and around the granulation tissue may explain, at least partially, why HO-1 upregulation and granulation tissue formation was seen in a parallel manner.
HO system has been known to act cytoprotectively against various types of oxidative stress (32). HO system is thought to exert an antioxidant property through bilirubin generation and/or ferritin induction (32) and exert an antihypertensive property through carbon monoxide generation (20). Recent papers have shown that cardiac HO-1 may have roles in the prevention of arteriosclerosis (7) and improvement of cardiac xenograft survival (28). Several papers (18, 20, 22) have shown that HO-1 expression was regulated in the heart. However, there are only a few previous investigations that showed the effect of hemodynamic stress on cardiac HO-1 expression (12, 26). HO-1 was upregulated in both ventricles in response to pressure overload induced by pulmonary artery banding (12) and by the renal artery occlusion (25). In addition, HO-1 was upregulated in the heart of genetically hypertensive rats compared with their normotensive counterpart (26). All these experiments suggested the concept that hemodynamic and mechanical forces upregulate cardiac HO-1 expression. In contrast, however, NE failed to affect cardiac HO-1 expression in the present study. Hemodynamic stress-induced HO-1 regulation in the heart may be variable according to the type, duration, and intensity of applied physical forces. By what mechanism ANG II, but not NE, exerted a proinflammatory effect has not been investigated in the present study. Because ANG II, but not NE, increases superoxide production in the arterial wall (24), different levels of oxidative stress induced by either ANG II or NE may explain the different effects of these hormones.
It has been reported that ANG II plays a pivotal role in an adverse
structural remodeling of the heart such as myocardial necrosis
(30), myofibroblast proliferation,
interstitial/perivascular fibrosis (2), and mobilization
of inflammatory cells (21). The finding that hydralazine
only partially suppressed ANG II-induced granulation tissue formation
supported the notion that ANG II induces cardiac inflammation by its
direct action (5, 13). In addition, our
results also suggested that pressure overload may exacerbate ANG
II-induced myocardial damage. Campbell et al.(3) reported
that ANG II stimulated expression of transforming growth factor-
1
(TGF-1) in cardiac myofibroblasts. Because TGF-1 stimulation increased HO-1 expression in fibroblasts in other tissue
(15), the possibility that ANG II-induced TGF-1 gene
expression acts as an autocrine/paracrine stimulus to upregulate
cardiac HO-1 should be addressed in future experiments.
The possible physiological role of ANG II-induced cardiac HO-1 upregulation may be threefold. First, because produced and released carbon monoxide may exert a vasodilatory effect by activating soluble guanylate cyclase (20), upregulated cardiac HO-1, together with aortic HO-1, may attenuate the pressor effect of ANG II. Second, because HO-1 has an anti-inflammatory property (28, 34), upregulated HO-1 may ameliorate ANG II-induced cardiac inflammatory response. It has been reported that the myocardial preservation afforded by nitric oxide was partially mediated by HO-dependent carbon monoxide generation in the setting of myocardial ischemia (17). Therefore, upregulated HO-1 may enhance protective cardiovascular homeostatic role of nitric oxide synthase in hypertension (8). The infiltrated inflammatory cells could modulate the synthetic and mitotic activity of the cardiac cells, which may result in cardiac hypertrophy (14, 27). Upregulated HO-1 or its product, carbon monoxide, may act against cell growth in epithelial cells (16) and in vascular smooth muscle cells (19). Therefore, third, upregulated cardiac HO-1 may counteract the hypertrophic effect of ANG II infusion and/or pressure overload.
We (1) recently found that administration of hemin, an HO
inducer, resulted in a marked increase of HO-1 expression in various
tissues (heart, carotid artery, aorta, liver, and kidney), which led to
the complete normalization of blood pressure in the ANG II-infused rat
(Ishizaka N, unpublished observation). To assess the cardioprotective
role of upregulated HO-1 without affecting blood pressure, the
adenoviral HO-1 gene transfer system is now under investigation in our
laboratory. Yet et al. (36) recently reported an
interesting observation that hypoxia induced myocardial dilatation and
infarction of right ventricles in HO-1 null (HO-1 
/) mice but not
in wild-type (HO-1 +/+) mice. In their paper, ventricular section of
HO-1 null mice showed inflammatory cell infiltration, myocardial
degradation, and collagen deposition. The fact that histological
features in the heart of ANG II-infused rat resembled those in the
heart of hypoxia-exposed HO-1 null mice may suggest the notion that ANG
II-induced HO-1 upregulation in the granulation tissue may act
protectively in the development of ANG II-induced cardiac inflammation
and remodeling.
In conclusion, chronic ANG II infusion induced formation of granulation tissue (myofibroblast proliferation, inflammatory cell migration, fibrous tissue deposition), where HO-1 was intensively expressed. These ANG II-induced histological changes and HO-1 upregulation were provoked in a pressor-independent manner and was augmented by pressure overload. Upregulated HO-1 may exert anti-inflammatory and antioxidant effects in the ANG II-induced granulation tissue.
| |
ACKNOWLEDGEMENTS |
|---|
We are highly appreciative of Noriko Itsubo for technical assistance and Yukihiro Kuwada for constructive comments.
| |
FOOTNOTES |
|---|
* N. Ishizaka and T. Aizawa contributed equally to this paper.
Address for reprint requests and other correspondence: N. Ishizaka, Dept. of Cardiovascular Medicine, Univ. of Tokyo, Graduate School of Medicine, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-8655, Japan (E-mail: nobuishizka-tky{at}umin.ac.jp).
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.
Received 21 July 1999; accepted in final form 2 February 2000.
| |
REFERENCES |
|---|
|
TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
1.
Aizawa, T,
Ishizaka N,
Taguchi J,
Kimura S,
Kurokawa K,
and
Ohno M.
Balloon injury does not induce heme oxygenase-1 expression, but administration of hemin inhibits neointimal formation in balloon- injured rat carotid artery.
Biochem Biophys Res Commun
261:
302-307,
1999[Web of Science][Medline].
2.
Campbell, SE,
Janicki JS,
and
Weber KT.
Temporal differences in fibroblast proliferation and phenotype expression in response to chronic administration of angiotensin II or aldosterone.
J Mol Cell Cardiol
27:
1545-1560,
1995[Web of Science][Medline].
3.
Campbell, SE,
and
Katwa LC.
Angiotensin II stimulated expression of transforming growth factor-beta1 in cardiac fibroblasts and myofibroblasts.
J Mol Cell Cardiol
29:
1947-1958,
1997[Web of Science][Medline].
4.
Coceani, F.
Carbon monoxide and dilation of blood vessels (Letter; comment).
Science
260:
739,
1993
5.
Crawford, DC,
Chobanian AV,
and
Brecher P.
Angiotensin II induces fibronectin expression associated with cardiac fibrosis in the rat.
Circ Res
74:
727-739,
1994
6.
Foresti, R,
Clark JE,
Green CJ,
and
Motterlini R.
Thiol compounds interact with nitric oxide in regulating heme oxygenase-1 induction in endothelial cells. Involvement of superoxide and peroxynitrite anions.
J Biol Chem
272:
18411-18417,
1997
7.
Hancock, WW,
Buelow R,
Sayegh MH,
and
Turka LA.
Antibody-induced transplant arteriosclerosis is prevented by graft expression of anti-oxidant and anti-apoptotic genes.
Nat Med
4:
1392-1396,
1998[Web of Science][Medline].
8.
Hayakawa, H,
and
Raij L.
The link among nitric oxide synthase activity, endothelial function, and aortic and ventricular hypertrophy in hypertension.
Hypertension
29:
235-241,
1997
9.
Ishikawa, K,
Navab M,
Leitinger N,
Fogelman AM,
and
Lusis AJ.
Induction of heme oxygenase-1 inhibits the monocyte transmigration induced by mildly oxidized LDL.
J Clin Invest
100:
1209-1216,
1997[Web of Science][Medline].
10.
Ishizaka, N,
de Leon H,
Laursen JB,
Fukui T,
Wilcox JN,
De Keulenaer G,
Griendling KK,
and
Alexander RW.
Angiotensin II-induced hypertension increases heme oxygenase-1 expression in rat aorta.
Circulation
96:
1923-1929,
1997
11.
Ishizaka, N,
and
Griendling KK.
Heme oxygenase-1 is regulated by angiotensin II in rat vascular smooth muscle cells.
Hypertension
29:
790-795,
1997
12.
Katayose, D,
Isoyama S,
Fujita H,
and
Shibahara S.
Separate regulation of heme oxygenase and heat shock protein 70 mRNA expression in the rat heart by hemodynamic stress.
Biochem Biophys Res Commun
191:
587-594,
1993[Web of Science][Medline].
13.
Katoh, M,
Egashira K,
Usui M,
Ichiki T,
Tomita H,
Shimokawa H,
Rakugi H,
and
Takeshita A.
Cardiac angiotensin II receptors are upregulated by long-term inhibition of nitric oxide synthesis in rats.
Circ Res
83:
743-751,
1998
14.
Kolattukudy, PE,
Quach T,
Bergese S,
Breckenridge S,
Hensley J,
Altschuld R,
Gordillo G,
Klenotic S,
Orosz C,
and
Parker-Thornburg J.
Myocarditis induced by targeted expression of the MCP-1 gene in murine cardiac muscle.
Am J Pathol
152:
101-111,
1998[Abstract].
15.
Kutty, RK,
Nagineni CN,
Kutty G,
Hooks JJ,
Chader GJ,
and
Wiggert B.
Increased expression of heme oxygenase-1 in human retinal pigment epithelial cells by transforming growth factor-beta.
J Cell Physiol
159:
371-378,
1994[Web of Science][Medline].
16.
Lee, PJ,
Alam J,
Wiegand GW,
and
Choi AM.
Overexpression of heme oxygenase-1 in human pulmonary epithelial cells results in cell growth arrest and increased resistance to hyperoxia.
Proc Natl Acad Sci USA
93:
10393-10398,
1996
17.
Maulik, N,
Engelman DT,
Watanabe M,
Engelman RM,
Rousou JA,
Flack JE, 3rd,
Deaton DW,
Gorbunov NV,
Elsayed NM,
Kagan VE,
and
Das DK.
Nitric oxide/carbon monoxide. A molecular switch for myocardial preservation during ischemia.
Circulation
94:
II398-II406,
1996.
18.
Maulik, N,
Sharma HS,
and
Das DK.
Induction of the haem oxygenase gene expression during the reperfusion of ischemic rat myocardium.
J Mol Cell Cardiol
28:
1261-1270,
1996[Web of Science][Medline].
19.
Morita, T,
Mitsialis SA,
Koike H,
Liu Y,
and
Kourembanas S.
Carbon monoxide controls the proliferation of hypoxic vascular smooth muscle cells.
J Biol Chem
272:
32804-32809,
1997
20.
Motterlini, R,
Gonzales A,
Foresti R,
Clark JE,
Green CJ,
and
Winslow RM.
Heme oxygenase-1-derived carbon monoxide contributes to the suppression of acute hypertensive responses in vivo [Erratum, Circ Res 83: 1289, 1998].
Circ Res
83:
568-577,
1998
21.
Nicoletti, A,
Heudes D,
Mandet C,
Hinglais N,
Bariety J,
and
Michel JB.
Inflammatory cells and myocardial fibrosis: spatial and temporal distribution in renovascular hypertensive rats.
Cardiovasc Res
32:
1096-1107,
1996
22.
Nishio, Y,
Kashiwagi A,
Taki H,
Shinozaki K,
Maeno Y,
Kojima H,
Maegawa H,
Haneda M,
Hidaka H,
Yasuda H,
Horiike K,
and
Kikkawa R.
Altered activities of transcription factors and their related gene expression in cardiac tissues of diabetic rats.
Diabetes
47:
1318-1325,
1998[Abstract].
23.
Poss, KD,
and
Tonegawa S.
Reduced stress defense in heme oxygenase 1-deficient cells.
Proc Natl Acad Sci USA
94:
10925-10930,
1997
24.
Rajagopalan, S,
Kurz S,
Munzel T,
Tarpey M,
Freeman BA,
Griendling KK,
and
Harrison DG.
Angiotensin II-mediated hypertension in the rat increases vascular superoxide production via membrane NADH/NADPH oxidase activation. Contribution to alterations of vasomotor tone.
J Clin Invest
97:
1916-1923,
1996[Web of Science][Medline].
25.
Raju, VS,
and
Maines MD.
Renal ischemia/reperfusion up-regulates heme oxygenase-1 (HSP32) expression and increases cGMP in rat heart.
J Pharmacol Exp Ther
277:
1814-1822,
1996
26.
Seki, T,
Naruse M,
Naruse K,
Yoshimoto T,
Tanabe A,
Tsuchiya K,
Hirose S,
Imaki T,
Nihei H,
and
Demura H.
Roles of heme oxygenase/carbon monoxide system in genetically hypertensive rats.
Biochem Biophys Res Commun
241:
574-578,
1997[Web of Science][Medline].
27.
Shioi, T,
Matsumori A,
Kihara Y,
Inoko M,
Ono K,
Iwanaga Y,
Yamada T,
Iwasaki A,
Matsushima K,
and
Sasayama S.
Increased expression of interleukin-1 beta and monocyte chemotactic and activating factor/monocyte chemoattractant protein-1 in the hypertrophied and failing heart with pressure overload.
Circ Res
81:
664-671,
1997
28.
Soares, MP,
Lin Y,
Anrather J,
Csizmadia E,
Takigami K,
Sato K,
Grey ST,
Colvin RB,
Choi AM,
Poss KD,
and
Bach FH.
Expression of heme oxygenase-1 can determine cardiac xenograft survival.
Nat Med
4:
1073-7,
1998[Web of Science][Medline].
29.
Stocker, R,
Yamamoto Y,
McDonagh AF,
Glazer AN,
and
Ames BN.
Bilirubin is an antioxidant of possible physiological importance.
Science
235:
1043-1046,
1987
30.
Tan, LB,
Jalil JE,
Pick R,
Janicki JS,
and
Weber KT.
Cardiac myocyte necrosis induced by angiotensin II.
Circ Res
69:
1185-1195,
1991
31.
Tenhunen, R,
Ross ME,
Marver HS,
and
Schmid R.
Reduced nicotinamide-adenine dinucleotide phosphate dependent biliverdin reductase: partial purification and characterization.
Biochemistry
9:
298-303,
1970[Medline].
32.
Vile, GF,
and
Tyrrell RM.
Oxidative stress resulting from ultraviolet A irradiation of human skin fibroblasts leads to a heme oxygenase-dependent increase in ferritin.
J Biol Chem
268:
14678-14681,
1993
33.
Wang, R,
Wu L,
and
Wang Z.
The direct effect of carbon monoxide on KCa channels in vascular smooth muscle cells.
Pflügers Arch
434:
285-291,
1997[Web of Science][Medline].
34.
Willis, D,
Moore AR,
Frederick R,
and
Willoughby DA.
Heme oxygenase: a novel target for the modulation of the inflammatory response.
Nat Med
2:
87-90,
1996[Web of Science][Medline].
35.
Yachie, A,
Niida Y,
Wada T,
Igarashi N,
Kaneda H,
Toma T,
Ohta K,
Kasahara Y,
and
Koizumi S.
Oxidative stress causes enhanced endothelial cell injury in human heme oxygenase-1 deficiency.
J Clin Invest
103:
129-135,
1999[Web of Science][Medline].
36.
Yet, SF,
Perrella MA,
Layne MD,
Hsieh CM,
Maemura K,
Kobzik L,
Wiesel P,
Christou H,
Kourembanas S,
and
Lee ME.
Hypoxia induces severe right ventricular dilatation and infarction in heme oxygenase-1 null mice.
J Clin Invest
103:
R23-R29,
1999[Medline].
37.
Yoshida, T,
Takahashi S,
and
Kikuchi G.
Partial purification and reconstitution of the heme oxygenase system from pig spleen microsomes.
J Biochem (Tokyo)
75:
1187-1191,
1974
This article has been cited by other articles:
|
|
 |
|
  S. W. Ryter, J. Alam, and A. M. K. Choi Heme Oxygenase-1/Carbon Monoxide: From Basic Science to Therapeutic Applications Physiol Rev, April 1, 2006; 86(2): 583 - 650. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M Bolognesi, D Sacerdoti, M Di Pascoli, P Angeli, S Quarta, A Sticca, P Pontisso, C Merkel, and A Gatta Haeme oxygenase mediates hyporeactivity to phenylephrine in the mesenteric vessels of cirrhotic rats with ascites Gut, November 1, 2005; 54(11): 1630 - 1636. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Ishizaka, K. Saito, I. Mori, G. Matsuzaki, M. Ohno, and R. Nagai Iron Chelation Suppresses Ferritin Upregulation and Attenuates Vascular Dysfunction in the Aorta of Angiotensin II-Infused Rats Arterioscler Thromb Vasc Biol, November 1, 2005; 25(11): 2282 - 2288. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Turkseven, A. Kruger, C. J. Mingone, P. Kaminski, M. Inaba, L. F. Rodella, S. Ikehara, M. S. Wolin, and N. G. Abraham Antioxidant mechanism of heme oxygenase-1 involves an increase in superoxide dismutase and catalase in experimental diabetes Am J Physiol Heart Circ Physiol, August 1, 2005; 289(2): H701 - H707. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Ishizaka, K. Saito, E. Noiri, M. Sata, H. Ikeda, A. Ohno, J. Ando, I. Mori, M. Ohno, and R. Nagai Administration of ANG II induces iron deposition and upregulation of TGF-{beta}1 mRNA in the rat liver Am J Physiol Regulatory Integrative Comp Physiol, April 1, 2005; 288(4): R1063 - R1070. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Saito, N. Ishizaka, T. Aizawa, M. Sata, N. Iso-o, E. Noiri, I. Mori, M. Ohno, and R. Nagai Iron chelation and a free radical scavenger suppress angiotensin II-induced upregulation of TGF-{beta}1 in the heart Am J Physiol Heart Circ Physiol, April 1, 2005; 288(4): H1836 - H1843. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. J. Teran, R. A. Johnson, B. K. Stevenson, K. J. Peyton, K. E. Jackson, S. D. Appleton, W. Durante, and F. K. Johnson Heme oxygenase-derived carbon monoxide promotes arteriolar endothelial dysfunction and contributes to salt-induced hypertension in Dahl salt-sensitive rats Am J Physiol Regulatory Integrative Comp Physiol, March 1, 2005; 288(3): R615 - R622. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Li, H. Jiang, L. Yang, S. Quan, S. Dinocca, F. Rodriguez, N. G. Abraham, and A. Nasjletti Angiotensin II induces carbon monoxide production in the perfused kidney: relationship to protein kinase C activation Am J Physiol Renal Physiol, November 1, 2004; 287(5): F914 - F920. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C.-M. Hu, Y.-H. Chen, M.-T. Chiang, and L.-Y. Chau Heme Oxygenase-1 Inhibits Angiotensin II-Induced Cardiac Hypertrophy In Vitro and In Vivo Circulation, July 20, 2004; 110(3): 309 - 316. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. E. Larkin, B. C. Frank, R. M. Gaspard, I. Duka, H. Gavras, and J. Quackenbush Cardiac transcriptional response to acute and chronic angiotensin II treatments Physiol Genomics, July 8, 2004; 18(2): 152 - 166. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Yang, S. Quan, A. Nasjletti, M. Laniado-Schwartzman, and N. G. Abraham Heme Oxygenase-1 Gene Expression Modulates Angiotensin II-Induced Increase in Blood Pressure Hypertension, June 1, 2004; 43(6): 1221 - 1226. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. K. Johnson, W. Durante, K. J. Peyton, and R. A. Johnson Heme oxygenase-mediated endothelial dysfunction in DOCA-salt, but not in spontaneously hypertensive, rat arterioles Am J Physiol Heart Circ Physiol, May 1, 2004; 286(5): H1681 - H1687. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. M. Sikorski, T. Hock, N. Hill-Kapturczak, and A. Agarwal The story so far: molecular regulation of the heme oxygenase-1 gene in renal injury Am J Physiol Renal Physiol, March 1, 2004; 286(3): F425 - F441. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T Hayashi, K Sohmiya, A Ukimura, S Endoh, T Mori, H Shimomura, M Okabe, F Terasaki, and Y Kitaura Angiotensin II receptor blockade prevents microangiopathy and preserves diastolic function in the diabetic rat heart Heart, October 1, 2003; 89(10): 1236 - 1242. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Li Volti, F. Seta, M. L. Schwartzman, A. Nasjletti, and N. G. Abraham Heme Oxygenase Attenuates Angiotensin II-Mediated Increase in Cyclooxygenase-2 Activity in Human Femoral Endothelial Cells Hypertension, March 1, 2003; 41(3): 715 - 719. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Ishizaka, K. Saito, H. Mitani, I. Yamazaki, M. Sata, S.-i. Usui, I. Mori, M. Ohno, and R. Nagai Iron Overload Augments Angiotensin II-Induced Cardiac Fibrosis and Promotes Neointima Formation Circulation, October 1, 2002; 106(14): 1840 - 1846. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
, systole;
, diastole) and NE-infused (
, systole;
, diastole) rats. In B, there was no
significant difference in heart rate between ANG II- (
P < 0.001 vs. sham-operated control.
P < 0.01 vs. ANG
II-infused rat.
