Garlic elicits a nitric oxide-dependent relaxation and inhibits hypoxic pulmonary vasoconstriction in rats.
1. The aims of the present study were to determine the characteristics of garlic extract-induced relaxation in rat isolated pulmonary arteries, its susceptibility to changes in oxygen tension and its protective effect against hypoxic pulmonary vasoconstriction. 2. In normoxia, garlic extract (3-500 microg/mL) produced a dose- and nitric oxide (NO)-dependent relaxation. Following 60 min hypoxia, maximum garlic relaxation was reduced compared with control (mean (-SEM) -86 +/- 3 vs-69 +/- 2% of phenylephrine (PE) precontraction, respectively), but recovered after 60 min reoxygenation (-85 +/- 3% PE precontraction). 3. Acetylcholine (0.1 micromol/L)-induced NO-dependent relaxation was reduced from a control value of -76 +/- 1% to -46 +/- 4% during hypoxia and was further reduced to -35 +/- 2 % after reoxygenation. 4. In endothelium-intact arteries, hypoxic exposure resulted in a triphasic response: early transient contraction (+24 +/- 4%), followed by transient relaxation (-37 +/- 7%) and then sustained contraction (+62 +/- 5%). 5. Pretreatment with NG-nitro-L-arginine methyl ester abolished the early transient contraction, moderately attenuated the sustained contraction and had no effect on the transient relaxation. Mechanical endothelial disruption inhibited all hypoxia-induced vascular changes. 6. Garlic pretreatment had no effect on the early transient contraction (+25 +/- 4%), but inhibited the transient relaxation (-5 +/- 3%; P<0.05) and the sustained contraction (+26 +/- 5%; 7. Garlic also significantly inhibited endothelin-l-induced contractions in a dose-dependent manner. 8. These findings show that garlic extract modulates the production and function of both endothelium-derived relaxing and constricting factors and this may contribute to its protective effect against hypoxic pulmonary vasoconstriction.
Kim-Park
S
S
Department of Pharmacology and Toxicology, University of Alabama at Birmingham, 35294, USA. SKIMPARK@UAB.EDU
Ku
D D
DD
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure; D004305:Dose-Response Relationship, Drug; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D005737:Garlic / Q000627:therapeutic use*; D006976:Hypertension, Pulmonary / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D000860:Hypoxia / Q000150:complications*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology*; D010946:Plants, Medicinal; D011651:Pulmonary Artery / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D014664:Vasodilation / Q000187:drug effects*
D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D010936:Plant Extracts; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester