IRAP inhibition using HFI419 prevents moderate to severe
acetylcholine mediated vasoconstriction in a rabbit model

J 2017

IRAP inhibition using HFI419 prevents moderate to severe acetylcholine mediated vasoconstriction in a rabbit model

EL-HAWLI, A., T. QARADAKHI, A. HAYES, E. RYBALKA, R. SMITH et. al.

Basic information

Original name

IRAP inhibition using HFI419 prevents moderate to severe acetylcholine mediated vasoconstriction in a rabbit model

Authors

EL-HAWLI, A. (36 Australia), T. QARADAKHI (36 Australia), A. HAYES (36 Australia), E. RYBALKA (36 Australia), R. SMITH (36 Australia), M. CAPRNDA (703 Slovakia), R. OPATRILOVA (203 Czech Republic), K. GAZDIKOVA (703 Slovakia), M. BENCKOVA (703 Slovakia), Peter KRUŽLIAK (703 Slovakia, guarantor, belonging to the institution) and A. ZULLI (36 Australia)

Edition

BIOMEDICINE & PHARMACOTHERAPY, PARIS, ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER, 2017, 0753-3322

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30104 Pharmacology and pharmacy

Country of publisher

France

Confidentiality degree

není předmětem státního či obchodního tajemství

Impact factor

Impact factor: 3.457

RIV identification code

RIV/00216224:14110/17:00098630

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.1016/j.biopha.2016.11.142

UT WoS

000395523800004

Keywords in English

Insulin regulated amino peptidase; Endothelial dysfunction; Homocysteine; HFI419

Abstract

V originále

Coronary artery vasospasm (constriction) caused by reduced nitric oxide bioavailability leads to myocardial infarction. Reduced endothelial release of nitric oxide by the neurotransmitter acetylcholine, leads to paradoxical vasoconstriction as it binds to smooth muscle cell M3 receptors. Thus, inhibition of coronary artery vasospasm will improve clinical outcomes. Inhibition of insulin regulated aminopeptidase has been shown to improve vessel function, thus we tested the hypothesis that HFI419, an inhibitor of insulin regulated aminopeptidase, could reduce blood vessel constriction to acetylcholine. The abdominal aorta was excised from New Zealand white rabbits (n = 15) and incubated with 3 mM Hcy to induce vascular dysfunction in vitro for 1 h. HFI419 was added 5 min prior to assessment of vascular function by cumulative doses of acetylcholine. In some rings, vasoconstriction to acetylcholine was observed in aortic rings after pre-incubation with 3 mM homocysteine. Incubation with HFI419 inhibited the vasoconstrictive response to acetylcholine, thus improving, but not normalizing, vascular function (11.5 +/- 8.9% relaxation vs 79.2 +/- 37% constriction, p < 0.05). Similarly, in another group with mild vasoconstriction, HFI419 inhibited this effect (34.9 +/- 4.6% relaxation vs 11.1 +/- 5.2%, constriction, p < 0.05). HFI419 had no effect on control aorta or aorta with mild aortic dysfunction. The present study shows that HFI419 prevents acetylcholine mediated vasoconstriction in dysfunctional blood vessels. HFI419 had no effect on normal vasodilation. Our results indicate a therapeutic potential of HFI419 in reducing coronary artery vasospasm. (C) 2016 Elsevier Masson SAS. All rights reserved.

Citovat

EL-HAWLI, A., T. QARADAKHI, A. HAYES, E. RYBALKA, R. SMITH, M. CAPRNDA, R. OPATRILOVA, K. GAZDIKOVA, M. BENCKOVA, Peter KRUŽLIAK and A. ZULLI. IRAP inhibition using HFI419 prevents moderate to severe acetylcholine mediated vasoconstriction in a rabbit model. BIOMEDICINE & PHARMACOTHERAPY. PARIS: ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER, 2017, vol. 86, FEB 2017, p. 23-26. ISSN 0753-3322. Available from: https://dx.doi.org/10.1016/j.biopha.2016.11.142.

@article{1398262,
   author = {ElandHawli, A. and Qaradakhi, T. and Hayes, A. and Rybalka, E. and Smith, R. and Caprnda, M. and Opatrilova, R. and Gazdikova, K. and Benckova, M. and Kružliak, Peter and Zulli, A.},
   article_location = {PARIS},
   article_number = {FEB 2017},
   doi = {http://dx.doi.org/10.1016/j.biopha.2016.11.142},
   keywords = {Insulin regulated amino peptidase; Endothelial dysfunction; Homocysteine; HFI419},
   language = {eng},
   issn = {0753-3322},
   journal = {BIOMEDICINE & PHARMACOTHERAPY},
   title = {IRAP inhibition using HFI419 prevents moderate to severe acetylcholine mediated vasoconstriction in a rabbit model},
   volume = {86},
   year = {2017}
}

TY  - JOUR
ID  - 1398262
AU  - El-Hawli, A. - Qaradakhi, T. - Hayes, A. - Rybalka, E. - Smith, R. - Caprnda, M. - Opatrilova, R. - Gazdikova, K. - Benckova, M. - Kružliak, Peter - Zulli, A.
PY  - 2017
TI  - IRAP inhibition using HFI419 prevents moderate to severe acetylcholine mediated vasoconstriction in a rabbit model
JF  - BIOMEDICINE & PHARMACOTHERAPY
VL  - 86
IS  - FEB 2017
SP  - 23-26
EP  - 23-26
PB  - ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
SN  - 07533322
KW  - Insulin regulated amino peptidase
KW  - Endothelial dysfunction
KW  - Homocysteine
KW  - HFI419
N2  - Coronary artery vasospasm (constriction) caused by reduced nitric oxide bioavailability leads to myocardial infarction. Reduced endothelial release of nitric oxide by the neurotransmitter acetylcholine, leads to paradoxical vasoconstriction as it binds to smooth muscle cell M3 receptors. Thus, inhibition of coronary artery vasospasm will improve clinical outcomes. Inhibition of insulin regulated aminopeptidase has been shown to improve vessel function, thus we tested the hypothesis that HFI419, an inhibitor of insulin regulated aminopeptidase, could reduce blood vessel constriction to acetylcholine. The abdominal aorta was excised from New Zealand white rabbits (n = 15) and incubated with 3 mM Hcy to induce vascular dysfunction in vitro for 1 h. HFI419 was added 5 min prior to assessment of vascular function by cumulative doses of acetylcholine. In some rings, vasoconstriction to acetylcholine was observed in aortic rings after pre-incubation with 3 mM homocysteine. Incubation with HFI419 inhibited the vasoconstrictive response to acetylcholine, thus improving, but not normalizing, vascular function (11.5 +/- 8.9% relaxation vs 79.2 +/- 37% constriction, p < 0.05). Similarly, in another group with mild vasoconstriction, HFI419 inhibited this effect (34.9 +/- 4.6% relaxation vs 11.1 +/- 5.2%, constriction, p < 0.05). HFI419 had no effect on control aorta or aorta with mild aortic dysfunction. The present study shows that HFI419 prevents acetylcholine mediated vasoconstriction in dysfunctional blood vessels. HFI419 had no effect on normal vasodilation. Our results indicate a therapeutic potential of HFI419 in reducing coronary artery vasospasm. (C) 2016 Elsevier Masson SAS. All rights reserved.
ER  -

EL-HAWLI, A., T. QARADAKHI, A. HAYES, E. RYBALKA, R. SMITH, M. CAPRNDA, R. OPATRILOVA, K. GAZDIKOVA, M. BENCKOVA, Peter KRUŽLIAK and A. ZULLI. IRAP inhibition using HFI419 prevents moderate to severe acetylcholine mediated vasoconstriction in a rabbit model. \textit{BIOMEDICINE \&{}amp; PHARMACOTHERAPY}. PARIS: ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER, 2017, vol.~86, FEB 2017, p.~23-26. ISSN~0753-3322. Available from: https://dx.doi.org/10.1016/j.biopha.2016.11.142.

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