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Depressor effect of chymase inhibitor in mice with high salt-induced moderate hypertension.
- Source :
-
American journal of physiology. Heart and circulatory physiology [Am J Physiol Heart Circ Physiol] 2015 Dec 01; Vol. 309 (11), pp. H1987-96. Date of Electronic Publication: 2015 Oct 02. - Publication Year :
- 2015
-
Abstract
- 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.<br /> (Copyright © 2015 the American Physiological Society.)
- Subjects :
- Albuminuria enzymology
Albuminuria prevention & control
Aldosterone blood
Aldosterone urine
Angiotensin II blood
Angiotensin II Type 1 Receptor Blockers pharmacology
Angiotensin-Converting Enzyme Inhibitors pharmacology
Angiotensinogen urine
Animals
Calcium Channel Blockers pharmacology
Chymases metabolism
Disease Models, Animal
Diuretics pharmacology
Heart Rate drug effects
Hypertension enzymology
Hypertension physiopathology
Male
Mice, Inbred C57BL
Mineralocorticoid Receptor Antagonists pharmacology
Renin-Angiotensin System drug effects
Time Factors
Antihypertensive Agents pharmacology
Blood Pressure drug effects
Chymases antagonists & inhibitors
Hypertension drug therapy
Serine Proteinase Inhibitors pharmacology
Sodium Chloride, Dietary
Subjects
Details
- Language :
- English
- ISSN :
- 1522-1539
- Volume :
- 309
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- American journal of physiology. Heart and circulatory physiology
- Publication Type :
- Academic Journal
- Accession number :
- 26432844
- Full Text :
- https://doi.org/10.1152/ajpheart.00721.2014