Aprotinin suppresses ACE-inhibitor cough triggered by TAME-esterase

Abstract 

N-α-Tosyl l-arginine methyl ester [TAME]-esterase appears to be an important biochemical marker, which displays potent contractile properties on bronchial tissues and aorta in vitro. TAME-esterase induced contractions have been shown to be mediated via a nitric oxide-cyclic GMP pathway. TAME-esterase has also been described to be a possible new cardiovascular risk factor among smokers. TAME-esterase has been reported to be an enzyme, which is involved during the sequence of events leading to the activation of the kinin–kallikrein system. Use of aprotinin (a kallikrein inhibitor) as well as aspirin and indomethacin (prostaglandin inhibitors) have shown that there is an inter-dependent relationship between the kinin–kallikrein system and the cyclo-oxygenase pathway involved during the sequence of reactions leading to TAME-esterase induced contractions. Our findings also lend support to the concept of calcium antagonism whereby verapamil, and nifedipine, mimicked in reversible fashion the effects of Ca²⁺ withdrawal on muscle excitability during TAME-esterase induced contractions on rat aorta in vitro. We concluded that the effects of captopril, an ACE inhibitor, on TAME-esterase induced contractions could thus be due to the degradation of bradykinin by the enzyme kininase being blocked. This paper proposes an integrated model of possible biochemical–pharmacological pathways, which involve events leading to TAME-esterase induced contractions. We hypothesize that TAME-esterase induced cough through sensitization of airway sensor nerves in hypertensive patients taking angiotensin-converting enzyme inhibitors can be inhibited by aprotinin.