THROMBOXANE ANTAGONISM AND COUGH INDUCED BY ANGIOTENSIN-CONVERTING-ENZYME INHIBITOR

Background The increased prostaglandin synthesis that might follow sti mulation of the arachidonic acid cascade by angiotensin-converting-enz yme inhibition (ACE-I) has been suggested to underlie the appearance o f cough on ACE-I treatment. We investigated whether the prostanoid thr omboxane was involved. Methods Nine patients with essential hypertensi on who had cough after enalapril 20 mg once a day (coughers) were trea ted, while continuing the enalapril, in a double-blind crossover study with placebo or picotamide, 600 mg twice daily. Picotamide is a plate let antiaggregant that acts through both inhibition of thromboxane syn thase and thromboxane-receptor antagonism. Thirteen hypertensive patie nts with no history of ACE-I-induced cough were also treated with enal april and served as controls. Cough frequency was measured by a visual analogue scale and by a daily cough diary. 24 h urinary recovery of 1 1-dehydrathromboxane-B-2 and 6-keto-PGF(1 alpha) were measured to asse ss any changes in endoperoxide metabolism during the study periods. Fi ndings 11-dehydro-thromboxane-B-2 (TXB2) recovery was significantly re duced by picotamide, which led disappearance of cough in eight patient s within Picotamide urinary recovery data suggested incomplete absorpt ion in the non-responder. At baseline and after rechallenge with enala pril, 11-dehydro-TXB2 excretion was in the same range in the controls and in the coughers, but the latter showed significantly lower excreti on of 6-keto-PGF(1 alpha) and their ratio of 11-dehydroTXB(2) to 6-ket o-PGF(1 alpha) was twice that of the controls (1.40 [95% CI 0.86-1.95] vs 0.61 [0.37-0.84]). Interpretation A thromboxane antagonist is effe ctive in ACE-I-induced cough. An imbalance between thromboxane and pro stacyclin may represent a marker of patients susceptible to ACE-I-indu ced cough.