Acute Oral Toxicity and Vasorelaxant Effects of Hydroethanolic Extract from Lannea microcarpa Engl. & K. Krause (Anacardiaceae) Trunk Barks in Mice Aortas: Possible Involvement of Intracellular Ca 2+ Mobilization

Lannea microcrapa Engl. & K. Krause (Anacardiaceae) is a fruit and medicinal plant widely used in Burkina Faso. This plant is traditionally used in the treatment of hypertension. The aim of the present study was to evaluate the vasorelaxant effects of the hydroethanolic extract from Lannea microcarpa trunk barks (HE_ELM) on the aorta isolated from NMRI mice. Phytochemical screening by HPTLC, assay of phenolic and flavonoid compounds, assessment of antioxidant activity (DPPH, ABTS, FRAP, and LPO), and myography of HE_ELM (1 - 2000 μg/mL) on mice thoracic aortas in the presence and absence of endothelium were carried out. Endothelium-dependent and endothelium-independant vasodilation were assessed by cumulative addition of Ach (1 nM - 10 μM) on aortic rings precontracted with the thromboxane analogue A2 agonist, 9,11-dideoxy9α,11α-methanoepoxy PGF2α (U46619). L-NAME was used to verify the involvement of NO production in the relaxation mechanism of the extract. Acute oral toxicity of HE_ELM was also evaluated. A phytochemical study revealed the presence of tannins, flavonoids, sterols and triterpenes, saponosides, and high levels of total phenolics and flavonoids. These compounds are thought to be responsible for the extract’s antioxidant and vasorelaxant properties. HE_ELM demonstrated significant antioxidant potential and induced aortic relaxation. Indeed, pharmacological parameters gave EC50 values ranging from 596.45 ± 95.82 μg/mL to 749.48 ± 133.40 μg/mL and Emax values from 85.51% ± 9.59% to 96.81% ± 8.60% for the three conditions of vasodilation of the extract (p > 0.05). A complete antagonism of the contractile effect of U46619 was noted with 1 mg/mL HE_ELM. These results suggest that HE_ELM induces aortic relaxation through a concentration-dependent, endothelium-independent mechanism, possibly involving intracellular calcium mobilization of vascular cells. Acute oral toxicity tests of HE_ELM (2000 mg/kg) showed no mortality or adverse effects, suggesting the extract’s safety and potential as a therapeutic agent for hypertension. This discovery scientifically validates the use of the plant in alternative medicine to treat hypertension.

Hydrogen sulfide and vascular relaxation

Objective To review the vasorelaxant effects of hydrogen sulfide （H2S） in arterial rings in the cardiovascular system under both physiological and pathophysiological conditions and the possible mechanisms involved. Data sources The data in this review were obtained from Medline and Pubmed sources from 1997 to 2011 using the search terms ＂hydrogen sulfide＂ and ＂vascular relaxation＂. Study selection Articles describing the role of hydrogen sulfide in the regulation of vascular activity and its vasorelaxant effects were selected. Results H2S plays an important role in the regulation of cardiovascular tone. The vasomodulatory effects of H2S depend on factors including concentration, species and tissue type. The H2S donor, sodium hydrosulfide （NariS）, causes vasorelaxation of rat isolated aortic rings in a dose-dependent manner. This effect was more pronounced than that observed in pulmonary arterial rings. The expression of KATp channel proteins and mRNA in the aortic rings was increased compared with pulmonary artery rings. H2S is involved in the pathogenesis of a variety of cardiovascular diseases. Downregulation of the endogenous H2S pathway is an important factor in the pathogenesis of cardiovascular diseases. The vasorelaxant effects of H2S have been shown to be mediated by activation of KATP channels in vascular smooth muscle cells and via the induction of acidification due to activation of the Cr/HCO3 exchanger. It is speculated that the mechanisms underlying the vasoconstrictive function of H2S in the aortic rings involves decreased NO production and inhibition of cAMP accumulation. Conclusion H2S is an important endogenous gasotransmitter in the cardiovascular system and acts as a modulator of vascular tone in the homeostatic regulation of blood pressure.