-
Something wrong with this record ?
Role of Nox inhibitors plumbagin, ML090 and gp91ds-tat peptide on homocysteine thiolactone induced blood vessel dysfunction
RM. Smith, P. Kruzliak, Z. Adamcikova, A. Zulli,
Language English Country Australia
Document type Journal Article
- MeSH
- Aorta, Abdominal drug effects physiopathology MeSH
- Quinoxalines pharmacology MeSH
- Glycoproteins pharmacology MeSH
- Homocysteine analogs & derivatives pharmacology MeSH
- Enzyme Inhibitors pharmacology MeSH
- Rabbits MeSH
- NADPH Oxidases antagonists & inhibitors MeSH
- Naphthoquinones pharmacology MeSH
- Dose-Response Relationship, Drug MeSH
- Animals MeSH
- Check Tag
- Rabbits MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
Antioxidants have not reduced the burden of cardiovascular disease, and current evidence suggests a beneficial role of oxidative stress, via NADPH oxidase (Nox) upregulation, in endothelial function. Homocysteine thiolactone (HcyT) induces blood vessel dysfunction and this correlates with increased vascular oxidative stress. This study aimed to determine if pharmacological inhibition of Nox could impair HcyT induced blood vessel dysfunction. Abdominal aorta were excised from New Zealand White rabbits (n = 6), cut into rings and sequentially mounted in organ baths. Rings were preincubated with 0.55 μmol/L homocysteine thiolactone for 1 h, or combinations of putative Nox inhibitors (plumbagin for Nox4, gp91ds-tat for Nox2, and ML090 for Nox1), 30 min prior to the addition of HcyT, followed by a dose response curve to acetylcholine on phenylephrine preconstricted rings. Plumbagin, ML090 + gp91ds-tat and HcyT reduced responses to acetylcholine, and Plumbagin + Hcyt caused constriction to acetylcholine, which was normalised to plumbagin by ML090. Plumbagin + ML090 or plumbagin + gp91ds-tat completely impaired the effect of acetylcholine. ML090 inhibited the effect of HcyT on reduced response to acetylcholine, whereas gp91ds-tat had no effect. This study concludes that inhibition of Nox1 prevents, whereas inhibition of Nox4 worsens, acetylcholine induced blood vessel relaxation caused by HcyT, while Nox2 inhibition has no effect. However combinations of Nox inhibitors worsen acetylcholine induced blood vessel relaxation. These results suggest that there is cross-talk between Nox isoforms during physiological and pathophysiological processes.
References provided by Crossref.org
- 000
- 00000naa a2200000 a 4500
- 001
- bmc16020764
- 003
- CZ-PrNML
- 005
- 20160726101409.0
- 007
- ta
- 008
- 160722s2015 at f 000 0|eng||
- 009
- AR
- 024 7_
- $a 10.1111/1440-1681.12427 $2 doi
- 024 7_
- $a 10.1111/1440-1681.12427 $2 doi
- 035 __
- $a (PubMed)25998981
- 040 __
- $a ABA008 $b cze $d ABA008 $e AACR2
- 041 0_
- $a eng
- 044 __
- $a at
- 100 1_
- $a Smith, Renee M $u Centre for Chronic Disease Prevention and Management, Western CHRE, College of Health and Biomedicine, Victoria University, St Albans, Vic., Australia.
- 245 10
- $a Role of Nox inhibitors plumbagin, ML090 and gp91ds-tat peptide on homocysteine thiolactone induced blood vessel dysfunction / $c RM. Smith, P. Kruzliak, Z. Adamcikova, A. Zulli,
- 520 9_
- $a Antioxidants have not reduced the burden of cardiovascular disease, and current evidence suggests a beneficial role of oxidative stress, via NADPH oxidase (Nox) upregulation, in endothelial function. Homocysteine thiolactone (HcyT) induces blood vessel dysfunction and this correlates with increased vascular oxidative stress. This study aimed to determine if pharmacological inhibition of Nox could impair HcyT induced blood vessel dysfunction. Abdominal aorta were excised from New Zealand White rabbits (n = 6), cut into rings and sequentially mounted in organ baths. Rings were preincubated with 0.55 μmol/L homocysteine thiolactone for 1 h, or combinations of putative Nox inhibitors (plumbagin for Nox4, gp91ds-tat for Nox2, and ML090 for Nox1), 30 min prior to the addition of HcyT, followed by a dose response curve to acetylcholine on phenylephrine preconstricted rings. Plumbagin, ML090 + gp91ds-tat and HcyT reduced responses to acetylcholine, and Plumbagin + Hcyt caused constriction to acetylcholine, which was normalised to plumbagin by ML090. Plumbagin + ML090 or plumbagin + gp91ds-tat completely impaired the effect of acetylcholine. ML090 inhibited the effect of HcyT on reduced response to acetylcholine, whereas gp91ds-tat had no effect. This study concludes that inhibition of Nox1 prevents, whereas inhibition of Nox4 worsens, acetylcholine induced blood vessel relaxation caused by HcyT, while Nox2 inhibition has no effect. However combinations of Nox inhibitors worsen acetylcholine induced blood vessel relaxation. These results suggest that there is cross-talk between Nox isoforms during physiological and pathophysiological processes.
- 650 _2
- $a zvířata $7 D000818
- 650 _2
- $a aorta abdominalis $x účinky léků $x patofyziologie $7 D001012
- 650 _2
- $a vztah mezi dávkou a účinkem léčiva $7 D004305
- 650 _2
- $a inhibitory enzymů $x farmakologie $7 D004791
- 650 _2
- $a glykoproteiny $x farmakologie $7 D006023
- 650 _2
- $a homocystein $x analogy a deriváty $x farmakologie $7 D006710
- 650 _2
- $a mužské pohlaví $7 D008297
- 650 _2
- $a NADPH-oxidasy $x antagonisté a inhibitory $7 D019255
- 650 _2
- $a naftochinony $x farmakologie $7 D009285
- 650 _2
- $a chinoxaliny $x farmakologie $7 D011810
- 650 _2
- $a králíci $7 D011817
- 655 _2
- $a časopisecké články $7 D016428
- 700 1_
- $a Kruzliak, Peter $u Department of Cardiovascular Diseases, International Clinical Research Center, St Anne's University Hospital and Masaryk University, Brno, Czech Republic.
- 700 1_
- $a Adamcikova, Zuzana $u Department of Public Health, Faculty of Medicine, Pavol Jozef Safarik University, Kosice, Slovak Republic. $7 gn_A_00001149
- 700 1_
- $a Zulli, Anthony $u Centre for Chronic Disease Prevention and Management, Western CHRE, College of Health and Biomedicine, Victoria University, St Albans, Vic., Australia.
- 773 0_
- $w MED00007158 $t Clinical and experimental pharmacology & physiology $x 1440-1681 $g Roč. 42, č. 8 (2015), s. 860-4
- 856 41
- $u https://pubmed.ncbi.nlm.nih.gov/25998981 $y Pubmed
- 910 __
- $a ABA008 $b sig $c sign $y a $z 0
- 990 __
- $a 20160722 $b ABA008
- 991 __
- $a 20160726101629 $b ABA008
- 999 __
- $a ok $b bmc $g 1155434 $s 945292
- BAS __
- $a 3
- BAS __
- $a PreBMC
- BMC __
- $a 2015 $b 42 $c 8 $d 860-4 $i 1440-1681 $m Clinical and experimental pharmacology & physiology $n Clin Exp Pharmacol Physiol $x MED00007158
- LZP __
- $a Pubmed-20160722
