Background　We　have　demonstrated　that　the　antihypertensive　effect　of　the　angiotensin-converting　enzyme　inhibitor,　captopril　(　CAP　),　is　associated　with　beneficial　effects　on　gut　pathology.　Coupled　with　the　evidence　that　CAP　exerts　prolonged　reduction　in　blood　pressure　(　BP　)　after　discontinuation　of　treatment,　we　investigate　whether　persistent　beneficial　actions　of　CAP　are　linked　to　alterations　of　gut　microbiota　and　improvement　of　hypertension-induced　gut　pathology.　Methods　and　Results　Spontaneously　hypertensive　rats　(　SHR　)　and　Wistar　Kyoto　rats　were　treated　with　CAP　(250 mg/kg/day)　for　4 weeks　followed　by　withdrawal　for　16 weeks.　Gut　microbiota,　gut　pathology,　BP,　and　brain　neuronal　activity　were　assessed.　CAP　resulted　in　a　≈60 mm Hg　decrease　in　systolic　BP　after　3 weeks　of　treatment　in　SHR　,　and　the　decrease　remained　significant　at　least　5 weeks　after　CAP　withdrawal.　In　contrast,　CAP　caused　modest　decrease　in　systolic　BP　in　Wistar　Kyoto.　16S　rRNA　gene-sequencing-based　gut　microbial　analyses　in　SHR　showed　sustained　alteration　of　gut　microbiota　and　increase　in　Allobaculum　after　CAP　withdrawal.　Phylogenetic　investigation　of　communities　by　reconstruction　of　unobserved　states　analysis　revealed　significant　increase　in　bacterial　sporulation　upon　CAP　treatment　in　SHR　.　These　were　associated　with　persistent　improvement　in　gut　pathology　and　permeability.　Furthermore,　manganese-enhanced　magnetic　resonance　imaging　showed　significantly　decreased　neuronal　activity　in　the　posterior　pituitary　of　SHR　4 weeks　after　withdrawal.　Conclusions　Decreased　BP　,　altered　gut　microbiota,　improved　gut　pathology　and　permeability,　and　dampened　posterior　pituitary　neuronal　activity　were　maintained　after　CAP　withdrawal　in　the　SHR　.　They　suggest　that　CAP　influences　the　brain-gut　axis　to　maintain　the　sustained　antihypertensive　effect　of　CAP　after　withdrawal.