Mechanisms of Garlic Extract‐induced Pulmonary Vasorelaxation: Role of Allicin and its related Organosulfur Metabolites.

We reported that garlic feeding prevented the development of both hypoxia‐ and monocrotaline‐induced pulmonary hypertension in rats. To investigate possible mechanisms of garlic vasoprotection, we studied the effects of allicin (found in fresh garlic), S‐allyl‐L‐cysteine (SAC, found in aged garlic), and various allicin‐related organosulfur compounds on rat pulmonary arteries (RPA). Allicin (0.01‐5 μg/ml), but not SAC (1‐100 μg/ml), produced a dose‐dependent relaxation in endothelium (EC)‐intact RPA reaching a maximum of −92±5% (M±SEM of 5 rats) with an IC50 of approximately 1.0 μg/ml. Removal of EC or pretreatment with L‐NAME slightly shifted the allicin dose‐response curve to the right. Addition of 1 mM D‐ or L‐cysteine abolished the allicin effect. Mass spectrometric analyses revealed the formation of S‐allylmercaptocysteine (SAMC) under this condition. SAMC had no effect on RPA. Alliin (an allicin precursor, 1‐1000 μg/ml) and allicin degradation sulfide products, diallyl disulfides and trisulfides (0.1‐30 μg/ml), also failed to elicit a significant vascular effect. Ajoene (1‐30 μg/ml) elicited a small relaxation, but mass spectrometric analyses showed that this was due to allicin contamination in the ajoene samples. Taken together, these findings demonstrate that allicin formation in fresh garlic, but not aged garlic, is likely responsible for garlic protection against pulmonary hypertension. (Supported by a grant from NCCAM, RO1‐AT001235)