{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T02:34:19Z","timestamp":1780626859270,"version":"3.54.1"},"reference-count":54,"publisher":"American Physiological Society","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"published-print":{"date-parts":[[2015,12,1]]},"abstract":"<jats:p> The aim of the present study was to determine whether long-term high salt intake in the drinking water induces hypertension in wild-type (WT) mice and whether a chymase inhibitor or other antihypertensive drugs could reverse the increase of blood pressure. Eight-week-old male WT mice were supplied with drinking water containing 2% salt for 12 wk (high-salt group) or high-salt drinking water plus an oral chymase inhibitor (TPC-806) at four different doses (25, 50, 75, or 100 mg\/kg), captopril (75 mg\/kg), losartan (100 mg\/kg), hydrochlorothiazide (3 mg\/kg), eplerenone (200 mg\/kg), or amlodipine (6 mg\/kg). Control groups were given normal water with or without the chymase inhibitor. Blood pressure and heart rate gradually showed a significant increase in the high-salt group, whereas a dose-dependent depressor effect of the chymase inhibitor was observed. There was also partial improvement of hypertension in the losartan- and eplerenone-treated groups but not in the captopril-, hydrochlorothiazide-, and amlodipine-treated groups. A high salt load significantly increased chymase-dependent ANG II-forming activity in the alimentary tract. In addition, the relative contribution of chymase to ANG II formation, but not actual average activity, showed a significant increase in skin and skeletal muscle, whereas angiotensin-converting enzyme-dependent ANG II-forming activity and its relative contribution were reduced by high salt intake. Plasma and urinary renin-angiotensin system components were significantly increased in the high-salt group but were significantly suppressed in the chymase inhibitor-treated group. In conclusion, 2% salt water drinking for 12 wk caused moderate hypertension and activated the renin-angiotensin system in WT mice. A chymase inhibitor suppressed both the elevation of blood pressure and heart rate, indicating a definite involvement of chymase in salt-sensitive hypertension. <\/jats:p>","DOI":"10.1152\/ajpheart.00721.2014","type":"journal-article","created":{"date-parts":[[2015,10,2]],"date-time":"2015-10-02T20:23:26Z","timestamp":1443817406000},"page":"H1987-H1996","source":"Crossref","is-referenced-by-count":23,"title":["Depressor effect of chymase inhibitor in mice with high salt-induced moderate hypertension"],"prefix":"10.1152","volume":"309","author":[{"given":"Sankar","family":"Devarajan","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Diseases, Fukuoka University Chikushi Hospital, Fukuoka, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eiji","family":"Yahiro","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Fukuoka University School of Medicine, Fukuoka, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshinari","family":"Uehara","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Fukuoka University School of Medicine, Fukuoka, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigehisa","family":"Habe","sequence":"additional","affiliation":[{"name":"Department of Parasitology, Fukuoka University School of Medicine, Fukuoka, Japan; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akira","family":"Nishiyama","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine, Kagawa University, Kagawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shin-ichiro","family":"Miura","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Fukuoka University School of Medicine, Fukuoka, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keijiro","family":"Saku","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Fukuoka University School of Medicine, Fukuoka, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hidenori","family":"Urata","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Diseases, Fukuoka University Chikushi Hospital, Fukuoka, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.32.3.514"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.92.4.825"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2007.04.062"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1081\/CEH-57423"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1126\/science.271.5248.502"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1976.40.4.601"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.2001.281.3.R987"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/32.10.2068"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1038\/nm1095-1009"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.107.091009"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1007\/s00251-006-0123-4"},{"key":"B12","unstructured":"Ganong WF. 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