title: Garlic and its active metabolite allicin produce endothelium- and nitric oxide-dependent relaxation in rat pulmonary arteries.
abstract: 1. The aims of the present study were to investigate the effects of fresh garlic and one of its active metabolites, allicin, on rat isolated pulmonary arteries (RPA). 2. In endothelium-intact and phenylephrine-precontracted RPA, the addition of a water or a 5% ethanol extract of fresh garlic (1-500 microg/mL) resulted in a dose-dependent relaxation reaching a maximum (mean +/- SEM) of -91 +/- 3 and -93 +/- 2%, respectively, with an ED(50) of 113 +/- 12 and 106 +/- 10 microg/mL, respectively. The vasorelaxation was readily reversible upon washing and no tachyphylaxis was noted. 3. An extract of the external garlic storage leaf produced a significantly greater relaxation than the inner stem. Microfiltration of extracts with a 10,000 molecular sieve did not attenuate relaxation. Inactivation of alliinase and allicin formation, with either boiling of the garlic clove for 30 min or 100% ethanol treatment, completely abolished relaxation. In contrast, similar treatment of crushed garlic with formed allicin retained the relaxation response. 4. Pure allicin produced a similar relaxation as garlic extract, with an EC(50) of approximately 0.8 microg/mL. Disruption of endothelium or N(G)-nitro-L-arginine methyl ester pretreatment attenuated the relaxation, whereas indomethacin had no effect. 5. Prior garlic (500 microg/mL) treatment enhanced acetylcholine relaxation by shifting the response curve to the left, but had no effect on nitric oxide (NO) donor-induced responses. 6. These results demonstrate that garlic and the active metabolite allicin are capable of eliciting a NO-dependent relaxation in RPA and that this response is likely to be mediated via garlic activation of NO formation rather than its stabilization.
authors.affiliation: Department of Pharmacology and Toxicology, University of Alabama at Birmingham, Alabama 35294, USA. DavidKu@UAB.EDU
authors.forename: David D
authors.initials: DD
authors.lastname: Ku
authors.forename: Tarek T
authors.initials: TT
authors.lastname: Abdel-Razek
authors.forename: Jun
authors.initials: J
authors.lastname: Dai
authors.forename: SangAe
authors.initials: S
authors.lastname: Kim-Park
authors.forename: Michael B
authors.initials: MB
authors.lastname: Fallon
authors.forename: Gary A
authors.initials: GA
authors.lastname: Abrams
mesh_terms: D000818:Animals; D004220:Disulfides; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D016166:Free Radical Scavengers / Q000494:pharmacology; D005737:Garlic / Q000378:metabolism*; D008297:Male; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D052250:Nitric Oxide Synthase Type III; D008517:Phytotherapy / Q000379:methods; D010936:Plant Extracts / Q000494:pharmacology; D018515:Plant Leaves; D018547:Plant Stems; D011651:Pulmonary Artery / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D013441:Sulfinic Acids / Q000378:metabolism / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology
chemical_list: D004220:Disulfides; D016166:Free Radical Scavengers; D010936:Plant Extracts; D013441:Sulfinic Acids; D009569:Nitric Oxide; C006452:allicin; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat