Vanilloid-Like Agents Inhibit in vitro Platelet Aggregation
Almaghrabi, S and Geraghty, DP and Ahuja, KDK and Adams, MJ, Vanilloid-Like Agents Inhibit in vitro Platelet Aggregation, Annual Combined ASM of the HSANZ/ANZBT/ASTH and the APSTH, 28-31 October 2012, Melbourne, Australia (2012) [Conference Extract]
Aim: 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.