Substance P (SP) Contributes To Rapidly Adapting Receptor (RAR) Activity In High Altitude Pulmonary Edema (HAPE)

Abstract

AimsTo investigate whether there is a change in i) basal RAR activity and ii) their responses to SP, in rabbits with HAPE.MethodsExperiments were performed in anesthetized, artificially ventilated and thoracotomized rabbits. After routine cannulations, the RAR activity was recorded from cervical vagus nerve. Increasing doses of SP were administered into the right atrium in control rabbits (C) breathing room air (n= 6) and in rabbits with HAPE (n= 6). To produce HAPE, rabbits were placed in a high altitude simulation chamber ‐ 15,000 feet, 36 hrs. In both the groups, SP doses were repeated after the administration of NK‐1 receptor antagonist, CP‐96345 (400 nmol/kg, Pfizer, Croton, USA).ResultsThe basal RAR activity in C was 6.34±0.46 impulses/breath and it increased to 10.0±0.64 impulses/breath (p<0.001) in HAPE. SP stimulated the RARs in both the groups. However, in HAPE, the RARs were stimulated even by sub‐threshold doses of SP. CP‐96345 attenuated the RAR activity in C but not in HAPE. RAR response to SP in C and HAPE groups. RAR activity in % Groups After SP (μg/kg) 0.02 0.04 0.08 Before CP‐96345 C 16.22±4.99 28.44±7.00 48.95±9.92 HAPE 51.14±5.10 *** 54.83±3.77** Not done After CP‐96345 C 18.10±8.59 24.44±9.27 20.58±4.98 HAPE 38.55±8.87 56.50±6.11* Not done RAR activity expressed as a percentage of their respective basal activities. p<0.05, p<0.01 and p<0.001, compared with the corresponding response in C. Conclusion1.HAPE stimulates RARs. 2. The RARs do not show adaptation to this stimulus. 3. Endogenous SP released during HAPE sensitizes the RARs to exogenous SP. Funded by DIPAS, Delhi.