Pomolic acid of Licania pittieri elicits endothelium-dependent relaxation in rat aortic rings.
Pomolic acid has recently shown hypotensive effect in rats. The purpose of this investigation was to determine the vascular effects of this triterpenoid and to examine its mode of action. Functional experiments in rat aortic rings precontracted with norepinephrine were performed to evaluate the vasorelaxant effect of pomolic acid. This triterpenoid induced a vasorelaxation (IC₅₀ = 2.45 μM) in a concentration- and endothelium-dependent manner and showed no effect on contractions evoked by KCl (25 mM). Pre-treatment of aortic rings with L-NAME (100 μM), methylene blue (100 μM) or glibenclamide (10 μM), totally prevented the vasorelaxation induced by pomolic acid, while indomethacin (10 μM) had no effect on this response. Additionally, pomolic acid relaxation was unaffected under the muscarinic- and β-adrenergic-receptor blocked ensured for atropine and propanolol respectively (10 μM each). In contrast, the vasorelaxant effect of pomolic acid was abolished under the purinergic-receptor blocked ensured for suramin (10 μM). Finally, apyrase (0.8 U/ml) an enzyme which hydrolyses ATP and ADP did not affect pomolic acid relaxation. In summary, pomolic acid has a potent endothelium-dependent vasorelaxant effect, possibly acting through the direct activation of endothelial purinergic receptors via NO-cGMP signaling pathway, which could be part of the mechanism underlying its hypotensive effect.
Laboratorio de Hemostasia y Genética Vascular, Centro de Biofísica y Bioquímica, Instituto Venezolano de Investigaciones Científicas, Venezuela.
Omar
O
Estrada
Juan Manuel
JM
González-Guzmán
Margarita
M
Salazar-Bookaman
Ana Z
AZ
Fernández
Alfonso
A
Cardozo
Claudia
C
Alvarado-Castillo
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001011:Aorta; D001081:Apyrase / Q000494:pharmacology; D001285:Atropine / Q000494:pharmacology; D045469:Chrysobalanaceae / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D006973:Hypertension / Q000378:metabolism / Q000517:prevention & control; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009638:Norepinephrine; D009828:Oleanolic Acid / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000494:pharmacology; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology*; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000378:metabolism; D011983:Receptors, Purinergic / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
D000959:Antihypertensive Agents; D010936:Plant Extracts; D011943:Receptors, Adrenergic, beta; D011976:Receptors, Muscarinic; D011983:Receptors, Purinergic; D014665:Vasodilator Agents; C115535:pomolic acid; D009828:Oleanolic Acid; D001285:Atropine; D011433:Propranolol; D001081:Apyrase; D009638:Norepinephrine; D007213:Indomethacin