L-NAME potentiates endothelin-stimulated thromboxane release from guinea pig lung.
The bronchoconstrictor response after systemic administration of endothelins (ETs) in the guinea pig is indirectly mediated by thromboxane A2 (TxA2) release through ETB receptor activation. ETs also trigger the release of nitric oxide (NO) in endothelial cells by activation of ETB receptors. A growing body of evidence indicates that endogenous NO plays a key role in the regulation of pulmonary function. In this study we investigated the effect of an NO synthase inhibitor, L-NAME, on the release of TxA2 from the isolated, perfused guinea pig lung induced either by ET-1, the selective ETB receptor agonist IRL-1620, bradykinin (BK), or a TxA2-mimetic, U 46619. A 30 min intra-arterial (intra-arterial) infusion of L-NAME (300 microM) potentiated the TxA2 release with ET-1, IRL 1620, and BK (5, 50, and 50 nM, respectively) infused for 3 min (i.a.). U 46619 (10 nM) was ineffective as a stimulant of pulmonary eicosanoid release. Interestingly, L-NAME did not potentiate the release of prostacyclin (PGI2) triggered by ET-1, IRL 1620, or BK. Our results suggest a predominant role of ETB receptor activation in the release of TxA2. Furthermore, we suggest that NO in the guinea pig lung is a potent modulator of the TxA2 releasing activity of ET-1, IRL 1620, and BK, three agonists known to stimulate the release of NO.
Lewis
K
K
Department of Pharmacology, Medical School, University of Sherbrooke, Québec, Canada.
Cadieux
A
A
Rae
G A
GA
D'Orléans-Juste
P
P
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D016232:Endothelins / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D010446:Peptide Fragments / Q000494:pharmacology; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000819:agonists; D013931:Thromboxanes / Q000378:metabolism*; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D016232:Endothelins; D004791:Enzyme Inhibitors; D010446:Peptide Fragments; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin; D013931:Thromboxanes; D014662:Vasoconstrictor Agents; C074308:sovateltide; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D019001:Nitric Oxide Synthase; D001920:Bradykinin; D019331:NG-Nitroarginine Methyl Ester