To verify the recently proposed concept that mast cell-derived renin facilitates angiotensin II-induced bronchoconstriction bronchial rings from male Sprague-Dawley rats were mounted in Mulvany myographs, and exposed to the mast cell degranulator compound 48/80 (300μg/ml), angiotensin I, angiotensin II, bradykinin or serotonin (5-hydroxytryptamine, 5-HT), in the absence or presence of the renin inhibitor aliskiren (10μmol/l), the ACE inhibitor captopril (10μmol/l), the angiotensin II type 1 (AT1) receptor blocker irbesartan (1μmol/l), the mast cell stabilizer cromolyn (0.3mmol/l), the 5-HT2A/2C receptor antagonist ketanserin (0.1μmol/l) or the α1-adrenoceptor antagonist phentolamine (1μmol/l). Bath fluid was collected to verify angiotensin generation. Bronchial tissue was homogenized to determine renin, angiotensinogen and serotonin content. Compound 48/80 contracted bronchi to 24±4% of the KCl-induced contraction. Ketanserin fully abolished this effect, while cromolyn reduced the contraction to 16±5%. Aliskiren, captopril, irbesartan and phentolamine did not affect this response, and the angiotensin I and II levels in the bath fluid after 48/80 exposure were below the detection limit. Angiotensin I and II equipotently contracted bronchi. Captopril shifted the angiotensin I curve ≈10-fold to the right, whereas irbesartan fully blocked the effect of angiotensin II. Bradykinin-induced constriction was shifted ≈100-fold to the left with captopril. Serotonin contracted bronchi, and ketanserin fully blocked this effect. Finally, bronchial tissue contained serotonin at micromolar levels, whereas renin and angiotensinogen were undetectable in this preparation. In conclusion, mast cell degranulation results in serotonin-induced bronchoconstriction, and is unlikely to involve renin-induced angiotensin generation.

Angiotensin, Bronchoconstriction, Mast cell, Renin, Serotonin,
European Journal of Pharmacology
Erasmus MC: University Medical Center Rotterdam

Krop, M, Özünal, Z.G, Chai, W, de Vries, R.R.P, Fekkes, D, Bouhuizen, A.M.B, … Danser, A.H.J. (2010). Mast cell degranulation mediates bronchoconstriction via serotonin and not via renin release. European Journal of Pharmacology, 640(1-3), 185–189. doi:10.1016/j.ejphar.2010.04.058