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BACKGROUND AND PURPOSEThe side effects of cyclooxygenase-2 (COX-2) inhibitors on the cardiovascular system could be associated with reduced prostaglandin (PG)I 2 synthesis. Microsomal PGE synthase-1 (mPGES-1) catalyses the formation of PGE 2 from COX-derived PGH 2 . This enzyme is induced under inflammatory conditions and constitutes an attractive target for novel anti-inflammatory drugs. However, it is not known whether mPGES-1 inhibitors could be devoid of cardiovascular side effects. The aim of this study was to compare, in vitro, the effects of mPGES-1 and COX-2 inhibitors on vascular tone in human blood vessels. EXPERIMENTAL APPROACHThe vascular tone and prostanoid release from internal mammary artery (IMA) and saphenous vein (SV) incubated for 30 min with inhibitors of mPGES-1 or COX-2 were investigated under normal and inflammatory conditions. KEY RESULTSIn inflammatory conditions, mPGES-1 and COX-2 proteins were more expressed, and increased levels of PGE 2 and PGI 2 were released. COX-2 and NOS inhibitors increased noradrenaline induced vascular contractions in IMA under inflammatory conditions while no effect was observed in SV. Interestingly, the mPGES-1 inhibitor significantly reduced (30-40%) noradrenalineinduced contractions in both vessels. This effect was reversed by an IP (PGI 2 receptor) antagonist but not modified by NOS inhibition. Moreover, PGI 2 release was increased with the mPGES-1 inhibitor and decreased with the COX-2 inhibitor, while both inhibitors reduced PGE 2 release. CONCLUSIONS AND IMPLICATIONSIn contrast to COX-2 inhibition, inhibition of mPGES-1 reduced vasoconstriction by increasing PGI 2 synthesis. Targeting mPGES-1 could provide a lower risk of cardiovascular side effects, compared with those of the COX-2 inhibitors.

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Background:In the last decade, a growing interest particularly in determining the cardiovascular effects of herbal extracts took place among researchers. Objective: Herein, we aimed to investigate the microvascular and blood pressure lowering effects of two differently processed extracts of the same herb, Alchemilla vulgaris (Rosaceaea), which was revealed to contain high levels of vasoactive compounds.Materials and Methods:For the purpose, endothelium intact rat mesenteric arteries were mounted in a myograph system and contracted with prostaglandin F2α (PGF2α: 3 × 10−5 M) or potassium chloride (K+: 40 mM). Then, aqueous and methanol extracts were added at 0.01–10 mg/ml concentrations in a cumulative manner.Results:Both extracts produced relaxations in PGF2α (3 × 10−5 M) precontracted arteries which were insensitive to the inhibitors of endothelium derived vasoactive substances namely, LG-nitro-L-arginine (10−4 M), ODQ (10−5 M) and indomethacin (10−5 M) or removal of endothelium. Opposite vascular effects were observed when extracts were applied in K+ precontracted arteries. In addition, oral administration of the methanol extract of Alchemilla vulgaris, but not the aqueous extract, reduced blood pressure significantly in L-NAME hypertensive rats.Conclusion:Our results demonstrated that the methanol extract of Alchemilla vulgaris has more prominent and favourable vascular effects in normal and experimental hypertensive conditions reinforcing its traditional use in cardiovascular disorders, in particular hypertension. These results most likely give rise to further studies to reveal its mechanism of action and clinical value of this herb.

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