Analysis of responses to St. John's Wort in the feline pulmonary vascular bed.

摘要

OBJECTIVE: To test the hypothesis that St. John's wort induces a depressor response in the feline pulmonary vascular bed and identify the pathways involved in the mediation or modulation of these effects. DESIGN: Prospective vehicle controlled study. SETTING: University research laboratory. SUBJECTS: Intact chest preparation; adult mongrel cats. INTERVENTIONS: In separate experiments, the effects of L-N5-(1-Iminoethyl) ornithine hydrochloride (L-NIO), a nitric oxide synthase inhibitor, glibenclamide, an ATP-sensitive K+ channel blocker, meclofenamate, a non-selective cyclo-oxygenase (COX) inhibitor, nicardipine, a calcium channel blocker, bicuculline, a GABAA receptor antagonist, and saclofen, a GABAB antagonist, were investigated on pulmonary arterial responses of St. John's wort (SJW), pinacidil, an ATP-sensitive K+ channel activator, bradykinin, an inducer of nitric oxide synthase, 3-aminopropyl (methyl) phosphinic acid, hydrochloride (SKF-97541), a GABAB receptor agonist and muscimol, a GABAA receptor agonist. MEASUREMENTS AND MAIN RESULTS: Lobar arterial perfusion pressure and systemic pressure were continuously monitored, electronically averaged and permanently recorded. Under elevated tone conditions in the isolated left lower lobe vascular bed of the cat, SJW induced a dose-dependent vasodepressor response that was not significantly altered after administration of L-NIO, glibenclamide, meclofenamate or saclofen. Responses to SJW were significantly reduced after administration of either nicardipine or bicuculline. When the calcium channel blocker nicardipine was administered in addition to the GABA blocker bicuculline, there was near complete attenuation of the SJW-induced vasodepressor responses. CONCLUSIONS: The results of the present study suggest that SJW has potent vasodepressor activity in the pulmonary vascular bed of the cat and that this response is mediated or modulated by both a calcium channel and GABA receptor sensitive pathway.