Aprotinin suppresses ACE-inhibitor cough triggered by TAME-esterase.

N-alpha-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.