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Vanilloid-Like Agents Inhibit in vitro Platelet Aggregation
conference contribution
posted on 2023-05-24, 11:43 authored by Almaghrabi, S, Dominic GeraghtyDominic Geraghty, Kiran AhujaKiran Ahuja, Adams, MJAim: Capsaicin (CAP), the ¡¥hot¡¦ principle found in chilli, and other vanilloids exert their effects through activation of transient receptor potential vanilloid 1 (TRPV1). It has been proposed that these agents inhibit platelet aggregation and may protect against the development of cardiovascular disease. The aim was to investigate the effects of a range of vanilloid-like agents on in vitro platelet aggregation. Methods: Collagen, ADP and arachidonic acid-induced platelet aggregation (%Max, %AUC, slope) was determined in the absence and presence of vanilloid-like agents [CAP, dihydrocapsaicin (DHC), N-oleoyldopamine (OLDA) and N-arachidonoyl-dopamine (NADA)]. Lactate dehydrogenase (LDH) release was measured to determine the direct toxic effects of vanilloids on platelets. The effect of the TRPV1 antagonist, SB-452533, on capsaicin- and OLDA-mediated inhibition of ADP-induced platelet aggregation was investigated. Finally, PF4 and £]-TG release were measured to determine the effects of vanilloids on alpha granule release. Results: ADP-induced aggregation was inhibited in a concentration-dependent manner by CAP (%Max, mean„bSEM; 0 vs 100 ƒÝmol/L, 83.8„b0.9% vs 45.2„b2.4%, pƒ¬0.001); OLDA (71.6„b8.2% vs 9.4„b1.4%, pƒ¬0.001); NADA (71.5„b5.9% vs 38.2„b1.4%, pƒ¬0.008). OLDA (89.3„b1.4% vs 45.5„b12.5%, p<0.001) and NADA (87.7„b0.8% vs 28.5„b8.2%, p<0.001) inhibited aggregation induced by collagen. Arachidonic acid-induced aggregation was inhibited by CAP (89.6„b0.9% vs 11„b0.8%, p<0.001); DHC (88.3„b2.1% vs 18.7„b6.9%, p<0.001); and NADA (84„b1.8% vs 21.9„b4.7%, p<0.001). The rate of aggregation (slope) was not affected by vanilloids. As LDH release was not affected by vanillioids, inhibition of aggregation was not due to a direct toxic effect. SB-452533 did not affect inhibition of ADP-induced aggregation by OLDA (%Max; 0 vs 10 ƒÝmol/L, 55.9„b2.1% vs 58.4„b1.4%) or CAP (65.2„b0.4% vs 65.6„b1.0%), suggesting that inhibition of aggregation by vanilloids is not TRPV1 mediated. Preliminary experiments suggest that ADP-stimulated PF4 release from platelets is impaired by CAP, DHC and OLDA whereas NADA enhances ADP-stimulated PF4 release. Conclusion: CAP, DHC, OLDA and NADA inhibit in vitro platelet aggregation, a mechanism that is not TRPV1 mediated nor due to a direct toxic effect on platelets. Vanilloids may inhibit platelet aggregation by interfering with granule release, although further investigations of this possible mechanism are required.
History
Publication title
Annual Combined ASM of the HSANZ/ANZBT/ASTH and the APSTHDepartment/School
School of Health SciencesPlace of publication
Melbourne, AustraliaEvent title
Annual Combined ASM of the HSANZ/ANZBT/ASTH and the APSTHEvent Venue
Melbourne, AustraliaDate of Event (Start Date)
2012-10-28Date of Event (End Date)
2012-10-31Repository Status
- Restricted