Topical Laryngopharyngeal Lisinopril Enhances Swallowing Reflux in Rats with Cerebral Hypoperfusion

Dysphagia, a risk factor for aspiration pneumonia in stroke patients, is associated with reduced substance P (SP) secretion from laryngopharyngeal sensory nerves. SP is degraded by angiotensin-converting enzyme (ACE) and its action is potentiated by ACE inhibitors. In this study, we investigated whether topical lisinopril can ameliorate the swallowing dysfunction induced by bilateral common carotid artery occlusion (2VO) in male Sprague-Dawley rats. Swallowing reflux was evoked by injection of 50 μL of water or citric acid into the laryngopharyngeal region and was identified by EMG activity of the mylohyoid muscle. 2VO rats showed a smaller number of swallows with a longer onset latency compared with the sham-operated rats. Pretreatment of the laryngopharyngeal region with lisinopril (1-1000 mM) dose-dependently increased the number of swallows and reduced the latency in 2VO rats, and these effects of lisinopril were completely abolished by topical FK-888 (a selective tachykinin NK1 receptor antagonist). These results suggest that topical lisinopril ameliorates the chronic cerebral hypoperfusion-induced attenuation of swallowing reflux in 2VO rats through potentiation of SP action.