Role of K+ and Ca2+ Channels in the Vasodilator Effects of Plectranthus barbatus (Brazilian Boldo) in Hypertensive Rats
CARDIOVASCULAR THERAPEUTICS(2023)
摘要
Plectranthus barbatus, popularly known as Brazilian boldo, is used in Brazilian folk medicine to treat cardiovascular disorders including hypertension. This study investigated the chemical profile by UFLC-DAD-MS and the relaxant effect by using an isolated organ bath of the hydroethanolic extract of P. barbatus (HEPB) leaves on the aorta of spontaneously hypertensive rats (SHR). A total of nineteen compounds were annotated from HEPB, and the main metabolite classes found were flavonoids, diterpenoids, cinnamic acid derivatives, and organic acids. The HEPB promoted an endothelium-dependent vasodilator effect (similar to 100%; EC50 similar to 347.10 mu g/mL). Incubation of L-NAME (a nonselective nitric oxide synthase inhibitor; EC50 similar to 417.20 mu g/mL), ODQ (a selective inhibitor of the soluble guanylate cyclase enzyme; EC50 similar to 426.00 mu g/mL), propranolol (a nonselective alpha-adrenergic receptor antagonist; EC50 similar to 448.90 mu g/mL), or indomethacin (a nonselective cyclooxygenase enzyme inhibitor; EC50 similar to 398.70 mu g/mL) could not significantly affect the relaxation evoked by HEPB. However, in the presence of atropine (a nonselective muscarinic receptor antagonist), there was a slight reduction in its vasorelaxant effect (EC50 similar to 476.40 mu g/mL). The addition of tetraethylammonium (a blocker of Ca2+-activated K+ channels; EC50 similar to 611.60 mu g/mL) or 4-aminopyridine (a voltage-dependent K+ channel blocker; EC50 similar to 380.50 mu g/mL) significantly reduced the relaxation effect of the extract without the interference of glibenclamide (an ATP-sensitive K+ channel blocker; EC50 similar to 344.60 mu g/mL) or barium chloride (an influx rectifying K+ channel blocker; EC50 similar to 360.80 mu g/mL). The extract inhibited the contractile response against phenylephrine, CaCl2, KCl, or caffeine, similar to the results obtained with nifedipine (voltage-dependent calcium channel blocker). Together, the HEPB showed a vasorelaxant effect on the thoracic aorta of SHR, exclusively dependent on the endothelium with the participation of muscarinic receptors and K+ and Ca2+ channels.
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