The cough reflex is upregulated by lisinopril microinjected into the caudal nucleus tractus solitarii of the rabbit

We have previously shown that cough potentiation induced by intravenous administration of the AT(1) receptor antagonist losartan is lower than that induced by the ACE inhibitor lisinopril in anesthetized and awake rabbits. Since losartan and lisinopril cross the blood-brain barrier, their central action on the cough reflex can be hypothesized. Mechanical stimulation of the tracheobronchial tree and citric acid inhalation were used to induce cough reflex responses in pentobarbital sodium-anesthetized, spontaneously breathing rabbits. Bilateral microinjections (30-50 nI) of losartan (5 mM), lisinopril (1 mM), bradykinin (0.05 mM), HOE-140 (0.2 mM, a bradykinin B2 receptor antagonist) and CP-99,994 (1 mM, an NK1 receptor antagonist) were performed into the caudal nucleus tractus solitarii, the predominant site of termination of cough-related afferents. Lisinopril, but not losartan increased the cough number. This effect was reverted by HOE-140 or CP-99,994. Cough potentiation was also induced by bradykinin. The results support for the first time a central protussive action of lisinopril mediated by an accumulation of bradykinin and substance P. (C) 2015 Elsevier B.V. All rights reserved.