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Effects of aerosolised substance P on lung resistance in guinea‐pigs: a comparison between inhibition of neutral endopeptidase and angiotensin‐converting enzyme
Author(s) -
Lötvall Jan O.,
Skoogh BengtEric,
Barnes Peter J.,
Chung K. Fan
Publication year - 1990
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1990.tb12053.x
Subject(s) - captopril , neprilysin , acetylcholine , substance p , chemistry , endocrinology , airway resistance , angiotensin converting enzyme , thiorphan , guinea pig , medicine , enzyme , respiratory system , enzyme inhibitor , inhalation , pharmacology , renin–angiotensin system , lung , neuropeptide , anesthesia , biochemistry , receptor , blood pressure
1 We have examined in guinea‐pigs, in vivo , the effects of inhibition of neutral endopeptidase (NEP) and angiotensin‐converting enzyme (ACE) on the airway response to aerosolised substance P (SP). We aerosolised captopril (4.6 m m , 60 breaths; 210 nmol) to inhibit ACE and acetorphan (0.3, 1 and 3 m m , 60 breaths; 9 nmol, 33 nmol and 110 nmol respectively) to inhibit NEP. We also examined the effect of the highest dose of acetorphan (110 nmol) on the response to aerosolised acetylcholine (ACh). 2 Responsiveness to SP (or ACh) was measured as the change in lung resistance (R L ) induced by nebulisation of increasing concentrations of SP (or ACh) before and after treatment with the inhibitor. PC 200 , defined as the provocative concentration inducing an increase in R L of 200% above baseline, was calculated for each challenge. 3 Administration of acetorphan before the second SP‐challenge induced a dose‐dependent decrease in PC 200 for SP amounting to 1.8 (±0.3) log units after treatment with 11 nmol acetorphan. Treatment with vehicle before the second SP‐challenge or with 3 m m acetorphan before the second ACh‐challenge had no significant effect on PC 200 . 4 Treatment with captopril (21 nmol) induced only a small, nonsignificant leftward shift of PC 200 to SP (0.3 ± 0.2 log units). 5 We conclude that a NEP‐like enzyme, but not ACE, regulates the response to aerosolised SP. We suggest that the same is true for SP released endogenously from sensory nerve endings in the airway epithelial layer.