Document Information


PMID 16139267  (  )
Title Protection against oxidative stress in diabetic rats: role of angiotensin AT(1) receptor and beta 1-adrenoceptor antagonism.
Abstract Oxidative stress and low-grade inflammation are hallmarks of diabetes mellitus. We explored protective, blood pressure-independent effects of the angiotensin II type 1 (AT(1)) receptor antagonist candesartan and the selective beta(1)-adrenoceptor antagonist metoprolol. Diabetes mellitus was induced in 8-week-old Sprague-Dawley rats after injection of streptozotocin. Diabetic rats were randomized to treatment with candesartan or metoprolol in sub-antihypertensive doses or to placebo treatment. In the quadriceps, musculature markers of oxidative stress and inflammation were determined. Function of the inherent vascular bed was measured in vivo in the autoperfused hindlimb. Increases in NAD(P)H activity, expression of its cytosolic subunit p22(phox) and of endothelial NO synthase e(NOS) displayed enhanced oxidative stress. Upregulated intercellular (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 and of inducible NOS (iNOS) revealed inflammatory processes. Diabetes was associated with severe impairment of endothelium-dependent and -independent vasodilatation. Candesartan, but not metoprolol, reduced NAD(P)H activity, attenuated diabetes-induced over-expression of p22(phox) and eNOS mRNA as well as ICAM-1, VCAM-1, iNOS and eNOS immunoreactivity and led to a substantial improvement of endothelium-dependent vasodilatation (+46.3% vs. placebo treatment; P<0.05). Angiotensin AT(1) receptor antagonism, but not beta(1)-adrenoceptor antagonism, ameliorates diabetes-generated oxidative stress, indicating a pivotal role of the renin-angiotensin system in the development of diabetic complications. Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12200 Berlin, Germany.

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Targets by SciMiner Summary

HUGO ID Symbol Target Name #Occur ActualStr
2577CYBAcytochrome b-245, alpha polypeptide24p22 phox |
7876NOS3nitric oxide synthase 3 (endothelial cell)22endothelial nitric oxide synthase | eNOS | eNOS-expression |
12663VCAM1vascular cell adhesion molecule 116VCAM-1 |
7873NOS2Anitric oxide synthase 2A (inducible, hepatocytes)14NOS | iNOS-expression |
5344ICAM1intercellular adhesion molecule 1 (CD54), human rhinovirus receptor13ICAM-1 |
2578CYBBcytochrome b-245, beta polypeptide (chronic granulomatous disease)7gp91 phox |
19986CYCScytochrome c, somatic5cytochrome c |
333AGTangiotensinogen (serpin peptidase inhibitor, clade A, member 8)5angiotensin ii |
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))5superoxide dismutase |
2707ACEangiotensin I converting enzyme (peptidyl-dipeptidase A) 12ACE | angiotensin converting enzyme |

 


Targets by SciMiner Full list

HUGO ID Symbol Name ActualStr Score FlankingText
2577CYBAcytochrome b-245, alpha polypeptidep220.3NAD(P)H NAD P H activity expression of its cytosolic subunit p22 phox and of endothelial NO synthase e(NOS) e NOS displayed
7873NOS2Anitric oxide synthase 2A (inducible, hepatocytes)NOS2.7subunit p22 phox and of endothelial NO synthase e(NOS) e NOS displayed enhanced oxidative stress
7873NOS2Anitric oxide synthase 2A (inducible, hepatocytes)NOS2.7vascular cell adhesion molecule (VCAM)-1 VCAM -1 and of inducible NOS (iNOS) iNOS revealed inflammatory processes
7873NOS2Anitric oxide synthase 2A (inducible, hepatocytes)iNOS2.7adhesion molecule (VCAM)-1 VCAM -1 and of inducible NOS (iNOS) iNOS revealed inflammatory processes
2577CYBAcytochrome b-245, alpha polypeptidep220.3reduced NAD(P)H NAD P H activity attenuated diabetes-induced over-expression of p22 phox and eNOS mRNA as well as ICAM-1 VCAM-1 iNOS
7876NOS3nitric oxide synthase 3 (endothelial cell)eNOS4.5P H activity attenuated diabetes-induced over-expression of p22 phox and eNOS mRNA as well as ICAM-1 VCAM-1 iNOS and eNOS immunoreactivity
5344ICAM1intercellular adhesion molecule 1 (CD54), human rhinovirus receptorICAM-12.3over-expression of p22 phox and eNOS mRNA as well as ICAM-1 VCAM-1 iNOS and eNOS immunoreactivity and led to a substantial
12663VCAM1vascular cell adhesion molecule 1VCAM-12.8of p22 phox and eNOS mRNA as well as ICAM-1 VCAM-1 iNOS and eNOS immunoreactivity and led to a substantial improvement
7873NOS2Anitric oxide synthase 2A (inducible, hepatocytes)iNOS2.7p22 phox and eNOS mRNA as well as ICAM-1 VCAM-1 iNOS and eNOS immunoreactivity and led to a substantial improvement of
7876NOS3nitric oxide synthase 3 (endothelial cell)eNOS4.5and eNOS mRNA as well as ICAM-1 VCAM-1 iNOS and eNOS immunoreactivity and led to a substantial improvement of endothelium-dependent vasodilatation
7876NOS3nitric oxide synthase 3 (endothelial cell)eNOS4.5The following primers were used for the PCR analysis eNOS 5_amp_#x2032 -GTGTTTGGCCGAGTCCTCACC-3_amp_#x2032 and 5_amp_#x2032 -CTCCTGCAAGGAAAAGCTCTG-3_amp_#x2032 NAD(P)H NAD P H oxidase
2577CYBAcytochrome b-245, alpha polypeptidep220.35_amp_#x2032 -GTGTTTGGCCGAGTCCTCACC-3_amp_#x2032 and 5_amp_#x2032 -CTCCTGCAAGGAAAAGCTCTG-3_amp_#x2032 NAD(P)H NAD P H oxidase p22 phox subunit 5_amp_#x2032 -ATGGGCAACTTGAAGAGCGTGGC-3_amp_#x2032 and 5_amp_#x2032 -TCCATGTG GAGCCCTTCTT -3_amp_#x2032 NAD(P)H
5344ICAM1intercellular adhesion molecule 1 (CD54), human rhinovirus receptorICAM-12.3at the given dilutions (45 45 min room temperature mouse-anti-rat ICAM-1 (Serotec, Serotec Oxford UK 1 100 mouse-anti-rat VCAM-1 (HISS HISS
12663VCAM1vascular cell adhesion molecule 1VCAM-12.8temperature mouse-anti-rat ICAM-1 (Serotec, Serotec Oxford UK 1 100 mouse-anti-rat VCAM-1 (HISS HISS Diagnostics Freiburg Germany 1 50 rabbit-anti-rat iNOS and
7873NOS2Anitric oxide synthase 2A (inducible, hepatocytes)iNOS2.7mouse-anti-rat VCAM-1 (HISS HISS Diagnostics Freiburg Germany 1 50 rabbit-anti-rat iNOS and rabbit-anti-rat eNOS (both both Alpha Diagnostic San Antonio USA
7876NOS3nitric oxide synthase 3 (endothelial cell)eNOS4.5HISS Diagnostics Freiburg Germany 1 50 rabbit-anti-rat iNOS and rabbit-anti-rat eNOS (both both Alpha Diagnostic San Antonio USA 1 50
2577CYBAcytochrome b-245, alpha polypeptidep220.3Gene expression of p22 phox gp91 phox and eNOS
7876NOS3nitric oxide synthase 3 (endothelial cell)eNOS4.5Gene expression of p22 phox gp91 phox and eNOS
2577CYBAcytochrome b-245, alpha polypeptidep220.3NAD(P)H NAD P H oxidase we examined two subunits (p22 p22 phox and gp91 phox of the multienzyme complex
2577CYBAcytochrome b-245, alpha polypeptidep220.3As shown in Fig 3 p22 phox mRNA was upregulated in vehicle-treated diabetic rats (8.8 8.8
2577CYBAcytochrome b-245, alpha polypeptidep220.3Treatment with candesartan but not metoprolol led to decreased p22 phox mRNA levels in diabetic rats
7876NOS3nitric oxide synthase 3 (endothelial cell)eNOS4.5RT-PCR and immunohistochemistry were performed to evaluate the inducibility of eNOS expression in skeletal muscle by diabetic conditions (immunohistological immunohistological results
5344ICAM1intercellular adhesion molecule 1 (CD54), human rhinovirus receptorICAM-12.3Immunoreactivity of ICAM-1 VCAM-1 eNOS and iNOS
12663VCAM1vascular cell adhesion molecule 1VCAM-12.8Immunoreactivity of ICAM-1 VCAM-1 eNOS and iNOS
7876NOS3nitric oxide synthase 3 (endothelial cell)eNOS4.5Immunoreactivity of ICAM-1 VCAM-1 eNOS and iNOS
7873NOS2Anitric oxide synthase 2A (inducible, hepatocytes)iNOS2.7Immunoreactivity of ICAM-1 VCAM-1 eNOS and iNOS
5344ICAM1intercellular adhesion molecule 1 (CD54), human rhinovirus receptorICAM-12.3Diabetic rats demonstrated a marked increase (6-fold) 6-fold in ICAM-1 protein expression compared to non-diabetic-controls (0.00338 0.00338 _amp_#xb1 0.00137 vs
5344ICAM1intercellular adhesion molecule 1 (CD54), human rhinovirus receptorICAM-12.3Diabetic rats treated with candesartan exhibited a significant lower ICAM-1 immunoreactivity whereas metoprolol had no effect on ICAM-1 expression
5344ICAM1intercellular adhesion molecule 1 (CD54), human rhinovirus receptorICAM-12.3significant lower ICAM-1 immunoreactivity whereas metoprolol had no effect on ICAM-1 expression
12663VCAM1vascular cell adhesion molecule 1VCAM-12.8As shown in Fig 4 VCAM-1 expression was also markedly increased under diabetic conditions (10-fold, 10-fold
12663VCAM1vascular cell adhesion molecule 1VCAM-12.8Candesartan treatment significantly reduced VCAM-1 protein expression
12663VCAM1vascular cell adhesion molecule 1VCAM-12.8Metoprolol showed no effect on VCAM-1 expression
7873NOS2Anitric oxide synthase 2A (inducible, hepatocytes)iNOS-expression2.7Diabetic rats had a significantly higher iNOS-expression (0.05244 0.05244 _amp_#xb1 0.02323 vs 0.0127 _amp_#xb1 0.00179 P _amp_#x3c
7876NOS3nitric oxide synthase 3 (endothelial cell)eNOS-expression2.2vs 0.0127 _amp_#xb1 0.00179 P _amp_#x3c 0.05 Fig 4 and eNOS-expression (0.02805 0.02805 _amp_#xb1 0.00371 vs 0.00549 _amp_#xb1 0.00095 P _amp_#x3c
7873NOS2Anitric oxide synthase 2A (inducible, hepatocytes)iNOS2.7with candesartan but not metoprolol led to a normalisation of iNOS and eNOS protein expression levels in quadriceps muscle tissue of
7876NOS3nitric oxide synthase 3 (endothelial cell)eNOS4.5but not metoprolol led to a normalisation of iNOS and eNOS protein expression levels in quadriceps muscle tissue of diabetic rats
5344ICAM1intercellular adhesion molecule 1 (CD54), human rhinovirus receptorICAM-12.3of oxidative stress accompanied by an increased eNOS-mRNA expression increased ICAM-1 VCAM-1 iNOS and eNOS protein expression and impaired endothelium-dependent vasodilatation
12663VCAM1vascular cell adhesion molecule 1VCAM-12.8oxidative stress accompanied by an increased eNOS-mRNA expression increased ICAM-1 VCAM-1 iNOS and eNOS protein expression and impaired endothelium-dependent vasodilatation which
7873NOS2Anitric oxide synthase 2A (inducible, hepatocytes)iNOS2.7stress accompanied by an increased eNOS-mRNA expression increased ICAM-1 VCAM-1 iNOS and eNOS protein expression and impaired endothelium-dependent vasodilatation which was
7876NOS3nitric oxide synthase 3 (endothelial cell)eNOS4.5by an increased eNOS-mRNA expression increased ICAM-1 VCAM-1 iNOS and eNOS protein expression and impaired endothelium-dependent vasodilatation which was antagonized by
2577CYBAcytochrome b-245, alpha polypeptidep220.3increased expression of the NAD(P)H NAD P H oxidase subunit p22 phox which is in agreement with previous works ( Zhang
7876NOS3nitric oxide synthase 3 (endothelial cell)eNOS4.5NAD P H were paralleled by an increased expression of eNOS
7876NOS3nitric oxide synthase 3 (endothelial cell)eNOS4.5Identical findings of increased eNOS expression have been reported before in diabetic rats ( Hink
7876NOS3nitric oxide synthase 3 (endothelial cell)eNOS4.5to understand this apparent paradox of diabetes-induced super induction of eNOS concomitantly with endothelial dysfunction
7876NOS3nitric oxide synthase 3 (endothelial cell)eNOS4.5has become clear that in the setting of diabetes upregulated eNOS is dysfunctional or _amp_#x201c uncoupled_amp_#x201d and may be due to
7876NOS3nitric oxide synthase 3 (endothelial cell)eNOS4.5is a reasonable explanation for our observation of an upregulated eNOS in combination with endothelial dysfunction
7873NOS2Anitric oxide synthase 2A (inducible, hepatocytes)iNOS2.7In the present study we also found an increased iNOS expression
7873NOS2Anitric oxide synthase 2A (inducible, hepatocytes)iNOS2.7NO derived from iNOS can function as a pro-inflammatory mediator and by reacting with
7873NOS2Anitric oxide synthase 2A (inducible, hepatocytes)iNOS2.7It is well established that iNOS synthesizes 10- to 50-fold more NO than the constitutive eNOS
7876NOS3nitric oxide synthase 3 (endothelial cell)eNOS4.5iNOS synthesizes 10- to 50-fold more NO than the constitutive eNOS and that its expression is increased in the setting of
5344ICAM1intercellular adhesion molecule 1 (CD54), human rhinovirus receptorICAM-12.3production of pro-inflammatory cytokines and of leukocyte adhesion molecules (ICAM-1, ICAM-1 VCAM-1 as well as other inflammatory pathways in vascular endothelial
12663VCAM1vascular cell adhesion molecule 1VCAM-12.8of pro-inflammatory cytokines and of leukocyte adhesion molecules (ICAM-1, ICAM-1 VCAM-1 as well as other inflammatory pathways in vascular endothelial cells
5344ICAM1intercellular adhesion molecule 1 (CD54), human rhinovirus receptorICAM-12.3we were able to demonstrate enhanced vascular protein expression of ICAM-1 and VCAM-1 under diabetic conditions
12663VCAM1vascular cell adhesion molecule 1VCAM-12.8able to demonstrate enhanced vascular protein expression of ICAM-1 and VCAM-1 under diabetic conditions
2707ACEangiotensin I converting enzyme (peptidyl-dipeptidase A) 1ACE0.6inhibition of the renin_amp_#x2013 angiotensin system with angiotensin-converting enzyme (ACE) ACE inhibitors and angiotensin AT 1 receptor antagonists does not influence
7876NOS3nitric oxide synthase 3 (endothelial cell)eNOS4.5levels down-regulation of eNOS-mRNA expression and reducing protein expression of eNOS and iNOS
7873NOS2Anitric oxide synthase 2A (inducible, hepatocytes)iNOS2.7of eNOS-mRNA expression and reducing protein expression of eNOS and iNOS
2577CYBAcytochrome b-245, alpha polypeptidep220.3found only an upregulation of NAD(P)H NAD P H oxidase p22 phox while changes in gp91 phox remained insignificant ( Zhang
5344ICAM1intercellular adhesion molecule 1 (CD54), human rhinovirus receptorICAM-12.3namely enhanced neutrophil-endothelium cell adhesion through increased expression of endothelial ICAM-1 and VCAM-1
12663VCAM1vascular cell adhesion molecule 1VCAM-12.8neutrophil-endothelium cell adhesion through increased expression of endothelial ICAM-1 and VCAM-1
5344ICAM1intercellular adhesion molecule 1 (CD54), human rhinovirus receptorICAM-12.3previous studies the present results demonstrate enhanced endothelial expression of ICAM-1 and VCAM-1 in diabetic rats ( Zhang et al. 2003
12663VCAM1vascular cell adhesion molecule 1VCAM-12.8the present results demonstrate enhanced endothelial expression of ICAM-1 and VCAM-1 in diabetic rats ( Zhang et al. 2003
5344ICAM1intercellular adhesion molecule 1 (CD54), human rhinovirus receptorICAM-12.3We showed significant reductions in ICAM-1 and VCAM-1 protein expression following 48 days of treatment with
12663VCAM1vascular cell adhesion molecule 1VCAM-12.8We showed significant reductions in ICAM-1 and VCAM-1 protein expression following 48 days of treatment with low-dose candesartan
12663VCAM1vascular cell adhesion molecule 1VCAM-12.8In the same model increased expression of VCAM-1 was antagonized by an angiotensin AT 1 receptor antagonist
5344ICAM1intercellular adhesion molecule 1 (CD54), human rhinovirus receptorICAM-12.3that an immunohistological examination of the tissue expression pattern of ICAM-1 and VCAM-1 has been performed in an in vivo haemodynamically
12663VCAM1vascular cell adhesion molecule 1VCAM-12.8immunohistological examination of the tissue expression pattern of ICAM-1 and VCAM-1 has been performed in an in vivo haemodynamically characterized peripheral
2577CYBAcytochrome b-245, alpha polypeptidep220.3However although NAD(P)H NAD P H oxidase activity p22 phox and eNOS mRNA expression seemed to be normalized after
7876NOS3nitric oxide synthase 3 (endothelial cell)eNOS4.5although NAD(P)H NAD P H oxidase activity p22 phox and eNOS mRNA expression seemed to be normalized after treatment with metoprolol
2577CYBAcytochrome b-245, alpha polypeptidep220.3discrepancy we determined NAD(P)H NAD P H oxidase activity and p22 phox mRNA expression in the muscle and not in isolated
2577CYBAcytochrome b-245, alpha polypeptidep220.3mRNA expression of NAD(P)H NAD P H oxidase subunits (p22 p22 phox and gp91 phox and of endothelial nitric oxide synthase
7876NOS3nitric oxide synthase 3 (endothelial cell)eNOS4.5and gp91 phox and of endothelial nitric oxide synthase (eNOS) eNOS
7876NOS3nitric oxide synthase 3 (endothelial cell)eNOS4.5Transcripts of NAD(P)H NAD P H oxidase subunits and of eNOS were evaluated by real-time polymerase chain reaction
7873NOS2Anitric oxide synthase 2A (inducible, hepatocytes)iNOS2.7(VCAM)-1, VCAM -1 inducible nitric oxide (NO) NO synthase (iNOS) iNOS and endothelial NO synthase (eNOS), eNOS measured by semi-quantitative immunohistochemistry
7876NOS3nitric oxide synthase 3 (endothelial cell)eNOS4.5(NO) NO synthase (iNOS) iNOS and endothelial NO synthase (eNOS), eNOS measured by semi-quantitative immunohistochemistry and expressed as area fraction (AF)
12663VCAM1vascular cell adhesion molecule 1VCAM-12.8Fig 5._amp_#xa0 Representative aspects of VCAM-1 expression in rat quadriceps muscle
12663VCAM1vascular cell adhesion molecule 1VCAM-12.8VCAM-1 immunoreactivity is clearly present in the endothelium (magnification, magnification _amp_#xd7
333AGTangiotensinogen (serpin peptidase inhibitor, clade A, member 8)angiotensin ii1.0we explored protective blood pressure independent effects of the angiotensin ii type 1 at 1 receptor antagonist candesartan and the selective _amp_#x3b2; 1 adrenoceptor antagonist metoprolol.
2577CYBAcytochrome b-245, alpha polypeptidep22 phox1.0increases in nad p h activity expression of its cytosolic subunit p22 phox and of endothelial no synthase e nos displayed enhanced oxidative stress.
2577CYBAcytochrome b-245, alpha polypeptidep22 phox1.0candesartan but not metoprolol reduced nad p h activity attenuated diabetes induced over expression of p22 phox and enos mrna as well as icam 1 vcam 1 inos and enos immunoreactivity and led to a substantial improvement of endothelium dependent vasodilatation + 46.3% vs placebo treatment; p _amp_#x3c; 0.05 .
333AGTangiotensinogen (serpin peptidase inhibitor, clade A, member 8)angiotensin ii1.0angiotensin ii accelerates the development of diabetic complications by promoting the generation of superoxide anions by activation of the angiotensin at 1 receptor rajagopalan et al. 1996 .
2577CYBAcytochrome b-245, alpha polypeptidep22 phox1.0the following primers were used for the pcr analysis: enos: 5_amp_#x2032; gtgtttggccgagtcctcacc 3_amp_#x2032; and 5_amp_#x2032; ctcctgcaaggaaaagctctg 3_amp_#x2032; nad p h oxidase p22 phox subunit: 5_amp_#x2032; atgggcaacttgaagagcgtggc 3_amp_#x2032; and 5_amp_#x2032; tccatgtg gagcccttctt 3_amp_#x2032; nad p h oxidase gp91 phox subunit: 5_amp_#x2032; gaggtgggacaatacattttc 3_amp_#x2032;
2578CYBBcytochrome b-245, beta polypeptide (chronic granulomatous disease)gp91 phox1.0_#x2032; ctcctgcaaggaaaagctctg 3_amp_#x2032; nad p h oxidase p22 phox subunit: 5_amp_#x2032; atgggcaacttgaagagcgtggc 3_amp_#x2032; and 5_amp_#x2032; tccatgtg gagcccttctt 3_amp_#x2032; nad p h oxidase gp91 phox subunit: 5_amp_#x2032; gaggtgggacaatacattttc 3_amp_#x2032; and 5_amp_#x2032; ctgcttatcacagccacaggc 3_amp_#x2032;.
19986CYCScytochrome c, somaticcytochrome c1.0muscle nad p h oxidase activity was measured by superoxide dismutase inhibitable reduction of cytochrome c with nadh or nad p h as substrates.
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))superoxide dismutase1.0muscle nad p h oxidase activity was measured by superoxide dismutase inhibitable reduction of cytochrome c with nadh or nad p h as substrates.
19986CYCScytochrome c, somaticcytochrome c1.0nadh stimulated production of reactive oxygen species was determined by following increases in cytochrome c absorbance.
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))superoxide dismutase1.0the experiments were performed in parallel with and without superoxide dismutase.
19986CYCScytochrome c, somaticcytochrome c1.0the activity of nad p h oxidase was calculated as superoxide dismutase inhibitable cytochrome c reduction. 2.6.
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))superoxide dismutase1.0the activity of nad p h oxidase was calculated as superoxide dismutase inhibitable cytochrome c reduction. 2.6.
19986CYCScytochrome c, somaticcytochrome c1.0oxidative stress in terms of production of reactive oxygen species was measured by superoxide dismutase inhibitable reduction of cytochrome c with nadh or nad p h as substrates 48 days after induction of diabetes mellitus.
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))superoxide dismutase1.0oxidative stress in terms of production of reactive oxygen species was measured by superoxide dismutase inhibitable reduction of cytochrome c with nadh or nad p h as substrates 48 days after induction of diabetes mellitus.
2577CYBAcytochrome b-245, alpha polypeptidep22 phox1.0gene expression of p22 phox gp91 phox and enos
2578CYBBcytochrome b-245, beta polypeptide (chronic granulomatous disease)gp91 phox1.0gene expression of p22 phox gp91 phox and enos
2577CYBAcytochrome b-245, alpha polypeptidep22 phox1.0to further elucidate the role of nad p h oxidase we examined two subunits p22 phox and gp91 phox of the multienzyme complex.
2578CYBBcytochrome b-245, beta polypeptide (chronic granulomatous disease)gp91 phox1.0to further elucidate the role of nad p h oxidase we examined two subunits p22 phox and gp91 phox of the multienzyme complex.
2577CYBAcytochrome b-245, alpha polypeptidep22 phox1.0as shown in fig. 3 p22 phox mrna was upregulated in vehicle treated diabetic rats 8.8 _amp_#xb1; 1.9 vs 26.3 _amp_#xb1; 8.2 [arb units]; p _amp_#x3c; 0.05 whereas the changes in gp91 phox expression were not significant 48 days
2578CYBBcytochrome b-245, beta polypeptide (chronic granulomatous disease)gp91 phox1.0as shown in fig. 3 p22 phox mrna was upregulated in vehicle treated diabetic rats 8.8 _amp_#xb1; 1.9 vs 26.3 _amp_#xb1; 8.2 [arb units]; p _amp_#x3c; 0.05 whereas the changes in gp91 phox expression were not significant 48 days after induction of the diabetic state 0.023 _amp_#xb1; 0.011 vs 0.029 _amp_#xb1; 0.02; n.s. .
2577CYBAcytochrome b-245, alpha polypeptidep22 phox1.0treatment with candesartan but not metoprolol led to decreased p22 phox mrna levels in diabetic rats.
2578CYBBcytochrome b-245, beta polypeptide (chronic granulomatous disease)gp91 phox1.0expression of gp91 phox mrna remained unchanged during treatment with candesartan and metoprolol.
2577CYBAcytochrome b-245, alpha polypeptidep22 phox1.0in the present study we found increased nad p h oxidase activity and increased expression of the nad p h oxidase subunit p22 phox which is in agreement with previous works zhang et al. 2003 .
2707ACEangiotensin I converting enzyme (peptidyl-dipeptidase A) 1angiotensin converting enzyme1.0 show that candesartan did not influence endothelium independent vasodilatation which is in agreement with previous works demonstrating that inhibition of the renin_amp_#x2013;angiotensin system with angiotensin converting enzyme ace inhibitors and angiotensin at 1 receptor antagonists does not influence endothelium independent vasodilatation o'driscoll et al. 1999 and hornig et al. 2003 .
333AGTangiotensinogen (serpin peptidase inhibitor, clade A, member 8)angiotensin ii1.0our data further suggest a pivotal role of angiotensin ii for the development of diabetes induced endothelial dysfunction.
333AGTangiotensinogen (serpin peptidase inhibitor, clade A, member 8)angiotensin ii1.0both local vascular angiotensin ii production and angiotensin at 1 receptor expression are significantly increased in diabetic rats sechi et al. 1994 .
2577CYBAcytochrome b-245, alpha polypeptidep22 phox1.0interestingly other groups also found only an upregulation of nad p h oxidase p22 phox while changes in gp91 phox remained insignificant zhang et al. 2003 .
2578CYBBcytochrome b-245, beta polypeptide (chronic granulomatous disease)gp91 phox1.0interestingly other groups also found only an upregulation of nad p h oxidase p22 phox while changes in gp91 phox remained insignificant zhang et al. 2003 .
333AGTangiotensinogen (serpin peptidase inhibitor, clade A, member 8)angiotensin ii1.0induction of adhesion molecules through angiotensin ii via the at 1 receptor has been described in a rat model tummala et al. 1999 .
2577CYBAcytochrome b-245, alpha polypeptidep22 phox1.0however although nad p h oxidase activity p22 phox and enos mrna expression seemed to be normalized after treatment with metoprolol metoprolol could neither influence levels of inflammation under streptozotocin induced diabetic conditions nor could i
2577CYBAcytochrome b-245, alpha polypeptidep22 phox1.0several hypotheses are possible to explain this discrepancy: we determined nad p h oxidase activity and p22 phox mrna expression in the muscle and not in isolated vascular tissue.
19986CYCScytochrome c, somaticcytochrome c1.0oxidative stress in terms of production of reactive oxygen species was measured in samples of rat skeletal muscle m quadriceps by superoxide dismutase inhibitable reduction of cytochrome c with nadh or nad p h as substrates.
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))superoxide dismutase1.0oxidative stress in terms of production of reactive oxygen species was measured in samples of rat skeletal muscle m quadriceps by superoxide dismutase inhibitable reduction of cytochrome c with nadh or nad p h as substrates.
2577CYBAcytochrome b-245, alpha polypeptidep22 phox1.0fig. 3._amp_#xa0;mrna expression of nad p h oxidase subunits p22 phox and gp91 phox and of endothelial nitric oxide synthase enos .
2578CYBBcytochrome b-245, beta polypeptide (chronic granulomatous disease)gp91 phox1.0fig. 3._amp_#xa0;mrna expression of nad p h oxidase subunits p22 phox and gp91 phox and of endothelial nitric oxide synthase enos .
7876NOS3nitric oxide synthase 3 (endothelial cell)endothelial nitric oxide synthase1.0fig. 3._amp_#xa0;mrna expression of nad p h oxidase subunits p22 phox and gp91 phox and of endothelial nitric oxide synthase enos .