Analysis of responses of garlic derivatives in the pulmonary vascular bed of the rat.
Allicin, an extract from garlic, has been shown to be a systemic and pulmonary arterial vasodilator that acts by an unknown mechanism. In the present experiments, pulmonary vascular responses to allicin (10-100 microg), allyl mercaptan (0.3-1 mg), and diallyl disulfide (0.3-1 mg) were studied in the isolated lung of the rat under constant-flow conditions. When baseline tone in the pulmonary vascular bed of the rat was raised to a high-steady level with the thromboxane A(2) mimic U-46619, dose-related decreases in pulmonary arterial pressure were observed. In terms of the mechanism of action of allicin vasodilator activity in the rat, responses to allicin were not significantly different after administration of the nitric oxide synthase inhibitor N(omega)-nitro-L-arginine methyl ester, the K(ATP)(+) channel antagonist U-37883A, or the cyclooxygenase inhibitor sodium meclofenamate, or when lung ventilation was interrupted. These data show that allicin has significant vasodilator activity in the pulmonary vascular bed of the rat, whereas allyl mercaptan and diallyl disulfide produced no significant changes in pulmonary arterial perfusion pressure. The present data suggest that pulmonary vasodilator responses to allicin are independent of the synthesis of nitric oxide, ATP-sensitive K(+) channels, activation of cyclooxygenase enzyme, or changes in bronchomotor tone in the pulmonary vascular bed of the rat.
Kaye
A D
AD
Departments of Anesthesiology and Pharmacology, Texas Tech University Health Sciences Center, Lubbock, Texas 79430, USA.
De Witt
B J
BJ
Anwar
M
M
Smith
D E
DE
Feng
C J
CJ
Kadowitz
P J
PJ
Nossaman
B D
BD
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000218:Adamantane / Q000031:analogs & derivatives / Q000494:pharmacology; D000498:Allyl Compounds / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology*; D001993:Bronchodilator Agents / Q000494:pharmacology; D019806:Cromakalim / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004220:Disulfides / Q000494:pharmacology; D004232:Diuretics / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005737:Garlic; D006976:Hypertension, Pulmonary / Q000188:drug therapy; D008173:Lung Diseases, Obstructive / Q000188:drug therapy; D008297:Male; D008469:Meclofenamic Acid / Q000494:pharmacology; D009025:Morpholines / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D010946:Plants, Medicinal; D011652:Pulmonary Circulation / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012119:Respiration; D013438:Sulfhydryl Compounds / Q000494:pharmacology; D013441:Sulfinic Acids / Q000494:pharmacology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D000498:Allyl Compounds; D000959:Antihypertensive Agents; D000975:Antioxidants; D001993:Bronchodilator Agents; D016861:Cyclooxygenase Inhibitors; D004220:Disulfides; D004232:Diuretics; D004791:Enzyme Inhibitors; D009025:Morpholines; D013438:Sulfhydryl Compounds; D013441:Sulfinic Acids; D014662:Vasoconstrictor Agents; D019806:Cromakalim; C006452:allicin; D008469:Meclofenamic Acid; C082658:U 37883A; C028009:diallyl disulfide; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000218:Adamantane; D019331:NG-Nitroarginine Methyl Ester