title: Perindopril increases the swallowing reflex by inhibiting substance P degradation and tyrosine hydroxylase activation in a rat model of dysphagia.
abstract: Patients with hypertension have a high risk of ischemic stroke and subsequent stroke-associated pneumonia. Stroke-associated pneumonia is most likely to develop in patients with dysphagia. The present study was designed to compare the ameliorative effects of different treatments in rat model of dysphagia. Spontaneously hypertensive rats were treated with bilateral common carotid artery occlusion (BCAO) to induce chronic cerebral hypoperfusion causing disorders of the swallowing reflex. Angiotensin-converting enzyme (ACE) inhibitors (perindopril, imidapril and enalapril), an angiotensin II type 1-receptor blocker (losartan), a vasodilator (hydralazine) and an indirect dopamine agonist (amantadine) were dissolved in drinking water and administered to the rats for six weeks. The blood pressure, the swallowing reflex under anesthesia, the substance P content in the striatum and the tyrosine hydroxylase (TH) expression in the substantial nigra were measured. Compared to the vehicle control, the decrease in the swallowing reflex induced by BCAO was attenuated significantly by enalapril, imidapril and perindopril, but only slightly by losartan. Hydralazine had no effect on the swallowing reflex. Amantadine significantly attenuated the decreased swallowing reflex but increased the blood pressure. Cerebral hypoperfusion for six weeks decreased the TH expression and substance P level. Perindopril improved both the TH expressions and substance P level, but imidapril, enalapril and amantadine only improved the substance P level. The present findings indicate that perindopril could be useful for preventing dysphagia in the chronic stage of stroke by attenuating the decrease in TH expression and the decrease in the substance P level.
authors.affiliation: Nephrology Research Laboratories, Kyowa Hakko Kirin Co., Ltd., Japan.
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Ikeda
authors.affiliation: Research Core function Laboratories, Kyowa Hakko Kirin Co., Ltd., Japan.
authors.forename: Natsuki
authors.initials: N
authors.lastname: Kojima
authors.affiliation: Planning and Administration Group, Kyowa Hakko Kirin Co., Ltd., Japan.
authors.forename: Kohji
authors.initials: K
authors.lastname: Saeki
authors.affiliation: Research Core function Laboratories, Kyowa Hakko Kirin Co., Ltd., Japan.
authors.forename: Miki
authors.initials: M
authors.lastname: Ishihara
authors.affiliation: Facility Management Group R&D Division, Kyowa Hakko Kirin Co., Ltd., 1188 Shimotogari, Nagaizumi-cho, Sunto-gun, Shizuoka-ken 411-8731, Japan. Electronic address: makoto.takayama@kyowa-kirin.co.jp.
authors.forename: Makoto
authors.initials: M
authors.lastname: Takayama
mesh_terms: D000547:Amantadine / Q000494:pharmacology; D057911:Angiotensin Receptor Antagonists / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003679:Deglutition / Q000187:drug effects / Q000502:physiology*; D003680:Deglutition Disorders / Q000378:metabolism / Q000503:physiopathology*; D004195:Disease Models, Animal; D004789:Enzyme Activation / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D008297:Male; D020913:Perindopril / Q000494:pharmacology*; D059748:Proteolysis / Q000187:drug effects*; D051381:Rats; D011918:Rats, Inbred SHR; D012018:Reflex / Q000187:drug effects*; D013373:Substance P / Q000378:metabolism*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism*; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D014665:Vasodilator Agents; D013373:Substance P; D000547:Amantadine; D014446:Tyrosine 3-Monooxygenase; D020913:Perindopril
keywords: Antihypertensive drug; Dopamine; Dysphagia; Hypertension; Substance P; Swallowing reflex