Garlic induced vasorelaxation: role of endothelium and nitric oxide

ABSTRACT

Garlic is a remarkable plant that has various beneficial effects and seems to function by multiple mechanisms that may be affected by its way of handling. The aim of the present study was to investigate the possible modification in activity of fresh garlic on vascular reactivity due to extraction in different organic and inorganic solvents or after microfiltration through specific molecular sieving devices. The possible roles of vascular endothelium and nitric oxide [NO] in mediating garlic extract-induced vasodilatation were also investigated. In addition, the interaction between garlic and other endothelium-dependent and endothelim-independent vasorelaxant agents was studied. Experiments were performed on ring preparations, with intact or denuded endothelium, isolated from rat pulmonary artery [PA] and thoracic aorta [TA]. Isolated vascular rings were precountracted with phenylephrine prior to testing possible vasorelaxation responses to different fresh garlic extracts. In all endothelium-intact ring preparation precontracted with phenylephrine, the addition of either water, 5% polyethylene glycol [PEG] or 5% ethanol extracts of whole fresh micro /ml] resulted in a slow developing dose-depndent relaxation reaching an average maximum of -82 +/- 5,-86+/7% and -88 +/- 6, respectively, in case of pulmonary artery, and -87 +/- 6.-90 +/- 7, respectively, in case of thoracic aorta. Extracts of either absolute [100%] ethanol or pure polyethylene glycol [PEG] of garlic failed to produce a significant fascular response [E[max]=10 +/- 2 and -8 +/- 1%, respectively, with the PA, and -13 +/- 2 and -10 +/- 1%, respectively, with the TA]. Microfiltration of the water extracts of fresh garlic with either a 10 000 or 1000 molecular weight sieving device did not alter the observed relaxation responses of either the PA or the TA. Mechanical disruption of intimal endothelium significantly attenuated garlic extract-induced vasorelaxation by 52-80% in case of PA, and by 56-72% in case of TA compared with the control endothelium-intact vessels. Pretreatment with the NO synthase inhibitor, N[G]-intero-L-arginine methyl ester [L-NAME] significantly reduced garlic extract-induced vasorelaxation by 26-71% in case of PA, and by 36-58% in case of TA. Pretreatment with L-cysteine almost abolished garlic-induced relaxations and decreased E[max] values by 91% and 89% in casse of the PA and the TA, respectively. On the other hand, pre-incubation of the tissues with superoxide dismutase [SOD] significantly potentiated garlic-induced relaxations and increased relaxation values by 14-40% in case of the PA, and by 12-42% in case of the TA, resectivley. Pretreatment with garlic [500] micro g/ml] significantly potentiated acetylcholine-induced relaxation in endothelium-intact vessels, obtained from either the PA or the TA, by shifting the dose-response curve to the left. On the other hand, in endothelium disrupted vessels, same garlic pre-treatment did not alter-s-nitroso-N-acetylpenicilamine [SNAP]-induced relaxations of the PA, while reduced mild potentiationin case of TA with no significant change of E[max]. It is concluded that 1] Garlic has potent vasorelaxant properties on both the pulmonary and systemic vasculature, 2] The active vasorelaxant ingredient[s] contained in fresh garlic extracts have molecular weight[s] less than 100, 3] To obtain the best vasorelaxant effects of fresh garlic, it should be extracted either in water or very dilute concentrations of organic solvents as ethanol and PEG, 4] Fresh garlic extracts can produce both endothelium-dependent and -independent vasodilatation-dependent and -independent vasodilatation; however, the endothelium-dependent component appears to play a greater role, 5] Endothelium-dependent relaxations of garlic are mediated mainly through increasing production and or/basal release of NO rather than stabilizing it