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.