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.

Základní údaje

Originální název

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

Autoři

EL-HAWLI, A. (36 Austrálie), T. QARADAKHI (36 Austrálie), A. HAYES (36 Austrálie), E. RYBALKA (36 Austrálie), R. SMITH (36 Austrálie), M. CAPRNDA (703 Slovensko), R. OPATRILOVA (203 Česká republika), K. GAZDIKOVA (703 Slovensko), M. BENCKOVA (703 Slovensko), Peter KRUŽLIAK (703 Slovensko, garant, domácí) a A. ZULLI (36 Austrálie)

Vydání

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

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30104 Pharmacology and pharmacy

Stát vydavatele

Francie

Utajení

není předmětem státního či obchodního tajemství

Impakt faktor

Impact factor: 3.457

Kód RIV

RIV/00216224:14110/17:00098630

Organizační jednotka

Lékařská fakulta

UT WoS

000395523800004

Klíčová slova anglicky

Insulin regulated amino peptidase; Endothelial dysfunction; Homocysteine; HFI419

Štítky

Příznaky

Mezinárodní význam, Recenzováno
Změněno: 15. 3. 2018 15:57, Soňa Böhmová

Anotace

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.