Modulation of transient receptor potential vanilloid-1 (TRPV1) by inhaled prostaglandin-E2 (PGE2) and bradykinin (BK) is associated with increased cough sensitivity to capsaicin (CPS) and autonomic dysregulation of cardiac rhythm in healthy subjects

Background: A neurogenic pathway, involving TRPV1 expressed in the airways, has been hypothesized to be implicated in acute cardiovascular events occurring after peaks of air pollution. Aims: To test whether inhaled prostaglandin E2 (PGE2) and bradykinin (BK) modulate TRPV1 activity in vivo by changing cough response to capsaicin (CPS) and whether sensitization of TRPV1 by PGE2 and BK affects heart rate variability (HRV). Methods: 17 healthy volunteers (median age 35 IQR, 29.5-47) inhaled 100 μg PGE2, 200 μg BK or diluent in a randomized double-blind fashion. Subsequently, the response to CPS was assessed by cough challenge. The results were expressed as n° of coughs caused by 30 μM of CPS. HRV, expressed by low (0.04–0.15 Hz) and high (0.15–0.40 Hz) normalized frequency components (nLF, sympathetic component, and nHF, vagal component), as well as nLF/nHF ratio (sympathovagal balance), was evaluated after inhalation of diluent, PGE2 and BK. Results: Inhalations of PGE2 and BK were associated with a highly significant increase in cough response induced by CPS: PGE2 (n° cough=4.20±0.42; p Conclusion: Inhalation of PGE2 and BK sensitizes TRPV1 and is associated with autonomic dysregulation of cardiac rhythm in healthy subjects.