)| PMID |
18302965 ( ) |
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| Title | Atrial natriuretic peptide prevents diabetes-induced endothelial dysfunction. |
| Abstract | Atrial natriuretic peptide (ANP) exerts beneficial effects on the cardiovascular system in part by exerting antioxidant activity. Given that oxidant stress is a key cause of endothelial dysfunction in diabetes, we investigated whether ANP improves endothelial function in rats with diabetes. Rats were injected with streptozotocin (55 mg/kg iv) to induce type 1 diabetes or the citrate vehicle as controls (n=12). After 4 weeks the diabetic rats were treated with ANP (10 pmol/kg/min sc, n=12) or the antioxidant tempol (1.5 mmol/kg/day sc, n=11), both by osmotic minipump, ramipril (1 mg/kg per day in the drinking water) or remained untreated (n=11). After a further 4 weeks, anaesthetised rats were killed by exsanguination and the thoracic aortae collected for examination of vascular activity and measurement of superoxide generation. Diabetic rats showed elevated plasma glucose concentration (45+/-3 mM) compared to controls (10+/-1 mM) and this was not affected by ANP (43+/-3 mM), ramipril (41+/-2 mM) or tempol (43+/-2 mM). Endothelium-dependent relaxation ex vivo in response to acetylcholine was impaired in diabetic rats (Rmax=66+/-4%) compared to control rats (Rmax=94+/-1%) but treatment with ANP (Rmax=80+/-4%), ramipril (Rmax=88+/-2%) or tempol (Rmax=81+/-5%) significantly improved those responses. Relaxant responses to the endothelium-independent vasodilator sodium nitroprusside were enhanced by treatment of diabetic rats with ANP or ramipril and their combination; but not by tempol. Superoxide generation was significantly elevated in aorta from untreated diabetic rats (649+/-146% of control). In diabetic rats, superoxide generation was significantly attenuated by ANP (to 229+/-78%) or tempol (to 186+/-64%). This study demonstrates that ANP improves vascular oxidant stress in concert with endothelial function, independent of any effect on plasma glucose levels. These studies may lead to new therapies, based on natriuretic peptide and/or antioxidant approaches, for ameliorating the vascular complications of diabetes. Australia. owen.woodman@rmit.edu.au |
NOTE: Color highlight is limited to the abstract and SciMiner text-mining mode. If you see much more identified targets below from "Targets by SciMiner Summary" and "Targets by SciMiner Full list", they may have been identified from the full text.
Targets by SciMiner Summary
| HUGO ID | Symbol | Target Name | #Occur | ActualStr |
|---|---|---|---|---|
| 7939 | NPPA | natriuretic peptide precursor A | 49 | atrial natriuretic peptide | ANP | ANP-mediated | |
| 2707 | ACE | angiotensin I converting enzyme (peptidyl-dipeptidase A) 1 | 11 | ACE | angiotensin converting enzyme | |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | 10 | nadph oxidase | |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | 8 | eNOS | |
| 4823 | HBA1 | hemoglobin, alpha 1 | 4 | HbA | |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | 3 | NOS | iNOS | nitric oxide synthase | |
| 6081 | INS | insulin | 3 | insulin | |
| 333 | AGT | angiotensinogen (serpin peptidase inhibitor, clade A, member 8) | 3 | angiotensin ii | ang ii | |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | 1 | gp91 phox | |
| 12805 | XDH | xanthine dehydrogenase | 1 | xanthine oxidase | |
Targets by SciMiner Full list
| HUGO ID | Symbol | Name | ActualStr | Score | FlankingText |
|---|---|---|---|---|---|
| 7939 | NPPA | natriuretic peptide precursor A | ANP | 0.9 | Atrial natriuretic peptide (ANP) ANP exerts beneficial effects on the cardiovascular system in part by |
| 7939 | NPPA | natriuretic peptide precursor A | ANP | 0.9 | key cause of endothelial dysfunction in diabetes we investigated whether ANP improves endothelial function in rats with diabetes |
| 7939 | NPPA | natriuretic peptide precursor A | ANP | 0.9 | After 4_amp_#xa0 weeks the diabetic rats were treated with ANP (10_amp_#xa0;pmol/kg/min 10_amp_#xa0 pmol kg min sc n = 12 or |
| 7939 | NPPA | natriuretic peptide precursor A | ANP | 0.9 | 10 _amp_#xb1 1_amp_#xa0 mM and this was not affected by ANP (43 43 _amp_#xb1 3_amp_#xa0 mM ramipril (41 41 _amp_#xb1 2_amp_#xa0 |
| 7939 | NPPA | natriuretic peptide precursor A | ANP | 0.9 | (R R max = 94 _amp_#xb1 1% but treatment with ANP (R R max = 80 _amp_#xb1 4% ramipril (R R |
| 7939 | NPPA | natriuretic peptide precursor A | ANP | 0.9 | sodium nitroprusside were enhanced by treatment of diabetic rats with ANP or ramipril and their combination but not by tempol |
| 7939 | NPPA | natriuretic peptide precursor A | ANP | 0.9 | In diabetic rats superoxide generation was significantly attenuated by ANP (to to 229 _amp_#xb1 78% or tempol (to to 186 |
| 7939 | NPPA | natriuretic peptide precursor A | ANP | 0.9 | This study demonstrates that ANP improves vascular oxidant stress in concert with endothelial function independent |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | eNOS | 3.2 | NADPH oxidase xanthine oxidase cyclooxygenase nitric oxide synthase (both both eNOS and iNOS isoforms and mitochondrial oxidative phosphorylation ( Schulz and |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | iNOS | 2.7 | xanthine oxidase cyclooxygenase nitric oxide synthase (both both eNOS and iNOS isoforms and mitochondrial oxidative phosphorylation ( Schulz and Keaney 2003 |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | NOS | 2.7 | In diabetes upregulation of NADPH oxidase and uncoupling of endothelial NOS (eNOS) eNOS are major contributors to endothelial dysfunction ( Wendt |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | eNOS | 3.2 | upregulation of NADPH oxidase and uncoupling of endothelial NOS (eNOS) eNOS are major contributors to endothelial dysfunction ( Wendt et al. |
| 7939 | NPPA | natriuretic peptide precursor A | ANP | 0.9 | We have recently reported that atrial natriuretic peptide (ANP) ANP is able to exert an antihypertrophic effect in rat cardiomyocytes |
| 7939 | NPPA | natriuretic peptide precursor A | ANP | 0.9 | Further evidence for antioxidant ANP effects has been provided from attenuated oxidative damage in liver |
| 7939 | NPPA | natriuretic peptide precursor A | ANP | 0.9 | It should be noted however that ANP has also been reported to increase generation of reactive oxygen |
| 7939 | NPPA | natriuretic peptide precursor A | ANP | 0.9 | aim of this study was to determine whether treatment with ANP prevents endothelial dysfunction in a rat model of type 1 |
| 7939 | NPPA | natriuretic peptide precursor A | ANP | 0.9 | We compared the effects of ANP with the antioxidant tempol which functions as a superoxide spintrap |
| 2707 | ACE | angiotensin I converting enzyme (peptidyl-dipeptidase A) 1 | ACE | 0.6 | the effect of treatment with the angiotensin converting enzyme (ACE) ACE inhibitor ramipril either alone or in combination with ANP |
| 7939 | NPPA | natriuretic peptide precursor A | ANP | 0.9 | (ACE) ACE inhibitor ramipril either alone or in combination with ANP |
| 2707 | ACE | angiotensin I converting enzyme (peptidyl-dipeptidase A) 1 | ACE | 0.6 | ACE inhibitors are considered first line treatment in diabetic patients with |
| 2707 | ACE | angiotensin I converting enzyme (peptidyl-dipeptidase A) 1 | ACE | 0.6 | (Ang Ang II stimulates NADPH oxidase activity and that consequently ACE inhibitors can reduce vascular synthesis of superoxide anions ( Cai |
| 7939 | NPPA | natriuretic peptide precursor A | ANP | 0.9 | The potential for ANP to modulate beneficial effects of ACE inhibition in the diabetic |
| 2707 | ACE | angiotensin I converting enzyme (peptidyl-dipeptidase A) 1 | ACE | 0.6 | The potential for ANP to modulate beneficial effects of ACE inhibition in the diabetic vasculature in either a positive or |
| 7939 | NPPA | natriuretic peptide precursor A | ANP | 0.9 | assigned to receive no treatment or to be treated with ANP ramipril ANP plus ramipril (to to determine whether the 2 |
| 7939 | NPPA | natriuretic peptide precursor A | ANP | 0.9 | receive no treatment or to be treated with ANP ramipril ANP plus ramipril (to to determine whether the 2 treatments had |
| 7939 | NPPA | natriuretic peptide precursor A | ANP | 0.9 | ANP (10 10 pmol/kg pmol kg per min and tempol (1.5_amp_#xa0;mmol/kg |
| 4823 | HBA1 | hemoglobin, alpha 1 | HbA | 0.3 | rats for subsequent biochemical analyses (plasma plasma glucose glycated haemoglobin HbA 1c Alfred Hospital Pathology Service Melbourne Australia |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | eNOS | 3.2 | Western analysis of eNOS |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | eNOS | 3.2 | For western analysis of eNOS protein level (monoclonal monoclonal antibody Transduction Laboratories Australia membranes were |
| 4823 | HBA1 | hemoglobin, alpha 1 | HbA | 0.3 | final body weight non-fasting plasma glucose and glycated haemoglobin (HbA HbA 1c arterial pressures and heart rates for all animals in |
| 7939 | NPPA | natriuretic peptide precursor A | ANP | 0.9 | Treatment with ANP or ramipril (alone alone or in combination or with tempol |
| 4823 | HBA1 | hemoglobin, alpha 1 | HbA | 0.3 | All of the streptozotocin-treated rats exhibited increased plasma glucose and HbA 1c that were not affected by any of the treatments |
| 7939 | NPPA | natriuretic peptide precursor A | ANP | 0.9 | ANP and tempol significantly reduced the generation of superoxide by the |
| 7939 | NPPA | natriuretic peptide precursor A | ANP | 0.9 | aortae but whilst ramipril in the absence or presence of ANP tended to decrease superoxide generation the levels were not significantly |
| 7939 | NPPA | natriuretic peptide precursor A | ANP | 0.9 | Fig 3 shows the effect of ANP tempol and ramipril in the absence and presence of ANP |
| 7939 | NPPA | natriuretic peptide precursor A | ANP | 0.9 | ANP tempol and ramipril in the absence and presence of ANP on endothelium-dependent relaxation |
| 7939 | NPPA | natriuretic peptide precursor A | ANP | 0.9 | relaxation was significantly enhanced by treatment of diabetic rats with ANP or ramipril and their combination (as as evidenced by the |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | eNOS | 3.2 | Aortic expression of eNOS |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | eNOS | 3.2 | Expression of eNOS protein tended to be lower in vehicle-treated diabetic rats compared |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | eNOS | 3.2 | None of the treatments significantly affected eNOS expression in comparison to control or vehicle-treated diabetic rats ( |
| 7939 | NPPA | natriuretic peptide precursor A | ANP | 0.9 | This study has demonstrated that ANP prevents endothelial dysfunction assessed by relaxant responses to ACh in |
| 7939 | NPPA | natriuretic peptide precursor A | ANP | 0.9 | The ability of ANP to enhance endothelium-dependent relaxation was associated with a decrease in |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | eNOS | 3.2 | but there was no change in the vascular expression of eNOS |
| 7939 | NPPA | natriuretic peptide precursor A | ANP | 0.9 | Surprisingly ANP treatment also significantly enhanced endothelium-independent relaxation in response to SNP |
| 7939 | NPPA | natriuretic peptide precursor A | ANP | 0.9 | The antioxidant tempol mimicked the ability of ANP to improve endothelium-dependent relaxation and decrease vascular superoxide levels but |
| 7939 | NPPA | natriuretic peptide precursor A | ANP | 0.9 | Thus whilst the antioxidant activity of ANP likely contributes to its protection against the diabetes-induced vascular dysfunction |
| 2707 | ACE | angiotensin I converting enzyme (peptidyl-dipeptidase A) 1 | ACE | 0.6 | The ACE inhibitor ramipril also improved endothelium-dependent relaxation without affecting responses to |
| 7939 | NPPA | natriuretic peptide precursor A | ANP | 0.9 | relaxation without affecting responses to SNP but when combined with ANP endothelium-independent relaxation was again potentiated suggesting an ANP-mediated action |
| 7939 | NPPA | natriuretic peptide precursor A | ANP-mediated | 0.9 | combined with ANP endothelium-independent relaxation was again potentiated suggesting an ANP-mediated action |
| 4823 | HBA1 | hemoglobin, alpha 1 | HbA | 0.3 | in rats caused the expected elevation of plasma glucose and HbA 1c and impairment of ACh-induced endothelium-dependent relaxation without affecting responses |
| 7939 | NPPA | natriuretic peptide precursor A | ANP | 0.9 | We also provide evidence that ANP treatment preserved endothelial function associated with a reduction in oxidant |
| 7939 | NPPA | natriuretic peptide precursor A | ANP | 0.9 | We have previously reported that ANP reduces superoxide generation by isolated cardiomyocytes and cardiac fibroblasts and |
| 7939 | NPPA | natriuretic peptide precursor A | ANP | 0.9 | superoxide generation by isolated cardiomyocytes and cardiac fibroblasts and that ANP is able to prevent the upregulation of the gp91 phox |
| 7939 | NPPA | natriuretic peptide precursor A | ANP | 0.9 | Thus it appears likely that ANP also inhibits NADPH oxidase activity in the aorta to reduce |
| 7939 | NPPA | natriuretic peptide precursor A | ANP | 0.9 | It should be noted that the dose of ANP (10 10 pmol/kg/min) pmol kg min used in this study |
| 7939 | NPPA | natriuretic peptide precursor A | ANP | 0.9 | generation of superoxide by the aorta in comparison to either ANP or tempol |
| 7939 | NPPA | natriuretic peptide precursor A | ANP | 0.9 | however just as effective at preserving endothelium-dependent relaxation as either ANP or tempol |
| 2707 | ACE | angiotensin I converting enzyme (peptidyl-dipeptidase A) 1 | ACE | 0.6 | production of superoxide through the stimulation of NADPH oxidase and ACE inhibitors are reported to reduce vascular oxidant stress by preventing |
| 2707 | ACE | angiotensin I converting enzyme (peptidyl-dipeptidase A) 1 | ACE | 0.6 | There is evidence however indicating that the beneficial actions of ACE inhibitors on endothelial function are not limited to antioxidant activity |
| 2707 | ACE | angiotensin I converting enzyme (peptidyl-dipeptidase A) 1 | ACE | 0.6 | In STZ-induced diabetic rats the ACE inhibitor enalapril and the angiotensin AT 1 receptor antagonist L-158809 |
| 7939 | NPPA | natriuretic peptide precursor A | ANP | 0.9 | Our data indicating that ramipril has less antioxidant activity than ANP or tempol but is as effective at improving endothelial function |
| 2707 | ACE | angiotensin I converting enzyme (peptidyl-dipeptidase A) 1 | ACE | 0.6 | is as effective at improving endothelial function suggests that the ACE inhibitor has a beneficial action on endothelial function through more |
| 7939 | NPPA | natriuretic peptide precursor A | ANP | 0.9 | A surprising finding from this study was that treatment with ANP either alone or in combination with ramipril significantly enhanced the |
| 7939 | NPPA | natriuretic peptide precursor A | ANP | 0.9 | Evidence in the literature largely suggests that ANP which activates particulate guanylate cyclase (pGC), pGC might either elicit |
| 7939 | NPPA | natriuretic peptide precursor A | ANP | 0.9 | Our findings from this study however suggest that ANP and SNP may elicit additive effects on vasodilatation |
| 7939 | NPPA | natriuretic peptide precursor A | ANP | 0.9 | Alternatively one might propose that improved endothelium-independent vasodilatation with ANP might simply reflect a natriuretic peptide-mediated reduction in vascular remodelling |
| 7939 | NPPA | natriuretic peptide precursor A | ANP | 0.9 | Regardless ANP clearly offers additional protective influence on endothelium-independent vasodilatation and is |
| 7939 | NPPA | natriuretic peptide precursor A | ANP | 0.9 | large and small vessels suggesting that the beneficial effects of ANP treatment observed in the aorta are also likely to be |
| 7939 | NPPA | natriuretic peptide precursor A | ANP | 0.9 | long-term treatment with a non-hypotensive dose of the natriuretic peptide ANP offers protective actions on endothelium-dependent and -independent vasodilatation and this |
| 7939 | NPPA | natriuretic peptide precursor A | atrial natriuretic peptide | 1.0 | atrial natriuretic peptide anp exerts beneficial effects on the cardiovascular system in part by exerting antioxidant activity. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | potential sources of oxidant stress in the vasculature include nadph oxidase xanthine oxidase cyclooxygenase nitric oxide synthase both enos and inos isoforms and mitochondrial oxidative phosphorylation [schulz and keaney 2003] and [landmesser et al. 2006] . |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | nitric oxide synthase | 1.0 | potential sources of oxidant stress in the vasculature include nadph oxidase xanthine oxidase cyclooxygenase nitric oxide synthase both enos and inos isoforms and mitochondrial oxidative phosphorylation [schulz and keaney 2003] and [landmesser et al. 2006] . |
| 12805 | XDH | xanthine dehydrogenase | xanthine oxidase | 1.0 | potential sources of oxidant stress in the vasculature include nadph oxidase xanthine oxidase cyclooxygenase nitric oxide synthase both enos and inos isoforms and mitochondrial oxidative phosphorylation [schulz and keaney 2003] and [landmesser et al. 2006] . |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | in diabetes upregulation of nadph oxidase and uncoupling of endothelial nos enos are major contributors to endothelial dysfunction [wendt et al. 2005] and [guzik and harrison 2006] . |
| 7939 | NPPA | natriuretic peptide precursor A | atrial natriuretic peptide | 1.0 | we have recently reported that atrial natriuretic peptide anp is able to exert an antihypertrophic effect in rat cardiomyocytes at least in part due to inhibition of nadph oxidase and superoxide generation laskowski et al. 2006 . |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | we have recently reported that atrial natriuretic peptide anp is able to exert an antihypertrophic effect in rat cardiomyocytes at least in part due to inhibition of nadph oxidase and superoxide generation laskowski et al. 2006 . |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | it should be noted however that anp has also been reported to increase generation of reactive oxygen species ros in human endothelial cells by activating nadph oxidase furst et al. 2005 . |
| 2707 | ACE | angiotensin I converting enzyme (peptidyl-dipeptidase A) 1 | angiotensin converting enzyme | 1.0 | in addition we investigated the effect of treatment with the angiotensin converting enzyme ace inhibitor ramipril either alone or in combination with anp. |
| 333 | AGT | angiotensinogen (serpin peptidase inhibitor, clade A, member 8) | ang ii | 1.0 | further it is well established that angiotensin ii ang ii stimulates nadph oxidase activity and that consequently ace inhibitors can reduce vascular synthesis of superoxide anions cai et al. 2003 . |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | further it is well established that angiotensin ii ang ii stimulates nadph oxidase activity and that consequently ace inhibitors can reduce vascular synthesis of superoxide anions cai et al. 2003 . |
| 333 | AGT | angiotensinogen (serpin peptidase inhibitor, clade A, member 8) | angiotensin ii | 1.0 | further it is well established that angiotensin ii ang ii stimulates nadph oxidase activity and that consequently ace inhibitors can reduce vascular synthesis of superoxide anions cai et al. 2003 . |
| 6081 | INS | insulin | insulin | 1.0 | diabetic rats are given sucrose supplemented 15_amp_#xa0;g/l drinking water for the first 48_amp_#xa0;h following injection to limit early mortality as the stores of insulin are released from damaged pancreatic cells. |
| 6081 | INS | insulin | insulin | 1.0 | blood glucose was monitored weekly by tail prick and when blood glucose exceeded 32_amp_#xa0;mm insulin ultratard hm was administered 2_amp_#xa0;u sc/day to prevent death due to diabetes. |
| 6081 | INS | insulin | insulin | 1.0 | at the end of 8_amp_#xa0;weeks of insulin deficient diabetes or sham tail vein blood was collected from conscious rats for subsequent biochemical analyses plasma glucose glycated haemoglobin hba 1c alfred hospital pathology service melbourne |
| 7939 | NPPA | natriuretic peptide precursor A | atrial natriuretic peptide | 1.0 | the following drugs and chemicals were used: acetylcholine perchlorate bdh chemicals atrial natriuretic peptide rat anp 28 bachem feinchemikalien ag bubendorf switzerland _amp_#x3b2; nicotinamide adenine dinucleotide phosphate nadph sigma ramipril gift from sanofi aventis frankfurt germany sodium nitroprusside |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | xidant stress is an important cause of endothelial dysfunction in diabetes [de vriese et al. 2000] and [rask madsen and king 2007] and that this might arise due to an increase in activity of vascular nadph oxidase hink et al. 2001 . |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | gp91 phox | 1.0 | we have previously reported that anp reduces superoxide generation by isolated cardiomyocytes and cardiac fibroblasts and that anp is able to prevent the upregulation of the gp91 phox subunit of nadph oxidase. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | we have previously reported that anp reduces superoxide generation by isolated cardiomyocytes and cardiac fibroblasts and that anp is able to prevent the upregulation of the gp91 phox subunit of nadph oxidase. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | thus it appears likely that anp also inhibits nadph oxidase activity in the aorta to reduce superoxide generation. |
| 333 | AGT | angiotensinogen (serpin peptidase inhibitor, clade A, member 8) | ang ii | 1.0 | ang ii is an important stimulus for the vascular production of superoxide through the stimulation of nadph oxidase and ace inhibitors are reported to reduce vascular oxidant stress by preventing that activa |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | ang ii is an important stimulus for the vascular production of superoxide through the stimulation of nadph oxidase and ace inhibitors are reported to reduce vascular oxidant stress by preventing that activation of nadph oxidase as well as increasing endogenous antioxidant enzyme activity landmesser et al. 2006 . |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | and ace inhibitors are reported to reduce vascular oxidant stress by preventing that activation of nadph oxidase as well as increasing endogenous antioxidant enzyme activity landmesser et al. 2006 . |
| 2707 | ACE | angiotensin I converting enzyme (peptidyl-dipeptidase A) 1 | angiotensin converting enzyme | 1.0 | angiotensin converting enzyme inhibitors|antioxidants|blood glucose|cyclic n oxides|spin labels|vasodilator agents|superoxides|nitroprusside|tempol|atrial natriuretic factor|ramipril|nitric oxide synthase type iii|nadph oxidase| |