RGD Reference Report - Effect of 5-lipoxygenase blockade on blood pressure and acetylcholine-evoked endothelium-dependent contraction in aorta from spontaneously hypertensive rats.

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Effect of 5-lipoxygenase blockade on blood pressure and acetylcholine-evoked endothelium-dependent contraction in aorta from spontaneously hypertensive rats.
Authors:	Lefebvre, B Caron, F Bessard, G Stanke-Labesque, F
Citation:	Lefebvre B, etal., J Hypertens. 2006 Jan;24(1):85-93.
RGD ID:	1626151
Pubmed:	PMID:16331105 (View Abstract at PubMed)
OBJECTIVE: Cysteinyl leukotrienes (cysLT) are pro-inflammatory and vasoactive products suspected to be involved in the regulation of vascular tone and blood pressure in hypertension. DESIGN: We investigated, in spontaneously hypertensive rats (SHR), the involvement of cysLT in the in-vivo regulation of blood pressure and the in-vitro endothelium-dependent contraction to acetylcholine in isolated aorta. METHODS: SHR and Wistar-Kyoto rats (WKY) were orally treated for 3 weeks with either the cysLT biosynthesis inhibitor MK-886 (0.1 mg/ml) or vehicle. After mean arterial blood pressure (MABP) measurement, aortic ring preparations were removed from all groups of animals, and contractions and relaxations were monitored subsequent to stimulation with acetylcholine. RESULTS: MABP was higher in SHR. Chronic treatment with MK-886 did not alter MABP in either SHR or WKY. In the presence of the N-nitro-L-arginine (L-NA, 100 micromol/l), and on prostaglandin F2alpha (PGF2alpha)-induced tone, acetylcholine evoked concentration-dependent contractions in intact aortic rings from SHR only. Pretreatment with either MK-886 (10 micromol/l), the 5-lipoxygenase (5-LO) inhibitor AA861 (10 micromol/l), or the cysLT1 receptor antagonist MK571 (1 micromol/l) reduced (P < 0.05) acetylcholine-induced contractions in intact aortic rings from SHR only. Acetylcholine-induced contractions were weaker (P < 0.01) in SHR chronically treated with MK-886 than in SHR. In the presence of L-NA, leukotriene (LT) D4 induced greater (P < 0.05) concentration-dependent contractions in aortic rings from SHR than from WKY. MK571 abolished LTD4-evoked contractions. CONCLUSION: These data suggested that 5-LO-derived products, through the activation of cysLT1 receptors, could be involved in the endothelium-dependent contraction to acetylcholine in aorta from SHR but not in the regulation of MABP in SHR.

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Object Symbol	Species	Term	Qualifier	Evidence	With	Notes	Source	Original Reference(s)
ALOX5	Human	hypertension		ISO	Alox5 (Rattus norvegicus)		RGD
Alox5	Rat	hypertension		IDA			RGD
Alox5	Mouse	hypertension		ISO	Alox5 (Rattus norvegicus)		RGD

Biological Process

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Object Symbol	Species	Term	Qualifier	Evidence	With	Notes	Source	Original Reference(s)
Alox5	Rat	positive regulation of vasoconstriction		IMP			RGD
Cysltr1	Rat	positive regulation of vasoconstriction		IMP			RGD

Genes (Rattus norvegicus)


Alox5 (arachidonate 5-lipoxygenase)	Cysltr1 (cysteinyl leukotriene receptor 1)

Genes (Mus musculus)


Alox5 (arachidonate 5-lipoxygenase)

Genes (Homo sapiens)


ALOX5 (arachidonate 5-lipoxygenase)

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Effect of 5-lipoxygenase blockade on blood pressure and acetylcholine-evoked endothelium-dependent contraction in aorta from spontaneously hypertensive rats.