Depressor effect of chymase inhibitor in mice with high salt-induced moderate hypertension.

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.

Depressor effect of the young leaves of Polygonum hydropiper Linn. in high-salt induced hypertensive mice.

A novel chymase inhibitor has been reported to have depressor effect in salt-induced hypertension. Therefore, we examined the hypothesis that chymase inhibitory dried young leaves of Polygonum hydropiper (PPH) or young leaves extract of Polygonum hydropiper (PHE) could reduce salt-induced hypertension. In this study, 8-wk old wild-type mice were allocated into three experiments and experiment I included groups, I- normal water drinking, II- high salt (2% NaCl) water (HSW) drinking, and III- HSW plus PPH (500 mg kg-1, orally) for 12-wk. Blood pressure (BP) and heart rate (HR) were measured at baseline and weekly up to wk-12. In experiment II, mice were given HSW for 12-wk followed by 8-wk treatment with PPH plus HSW (62.5, 125, 250 and 500 mg kg-1 for groups I, II, III and IV, respectively). BP and HR were measured at baseline and monthly until wk-12, following weekly for 8-wk. Experiment III comprised of four groups of mice for 12-wk HSW and 8-wk treatment with PHE plus HSW (2.5, 5, 10 and 20 mg kg-1 for groups I-IV, respectively). BP and HR were measured at baseline and monthly up to wk-12, following weekly for 8-wk. Significant reduction in BP and HR were observed in mice treated with PPH (500 mg kg-1) compared to HSW control. PPH reduced BP and HR dose dependently in hypertensive mice and the higher dose showed maximum reduction. PHE at its maximum dose (20 mg kg-1) significantly suppressed BP and HR. Over all, we found that the young leaves of Polygonum hydropiper suppressed salt-induced hypertension.

A blend of sesame oil and rice bran oil lowers blood pressure and improves the lipid profile in mild-to-moderate hypertensive patients.

BACKGROUND: Sesame oil and rice bran oil are known for their unsaturated fatty acids and antioxidants contents and have been reported to reduce the cardiovascular risk. OBJECTIVE: To determine the effect of a blend of 20% unrefined cold-pressed lignans-rich sesame oil and 80% physically refined γ-oryzanol-rich rice bran oil (Vivo) as cooking oil in mild-to-moderate hypertensive patients. METHODS: In this prospective, open-label dietary approach, 300 hypertensive patients and 100 normotensives were divided into groups as: (1) normotensives treated with sesame oil blend, (2) hypertensives treated with sesame oil blend, (3) hypertensives treated with nifedipine, a calcium channel blocker (20 mg/d), and (4) hypertensives receiving the combination of sesame oil blend and nifedipine (20 mg/d). Sesame oil blend was supplied to respective groups, and they were instructed to use it as the only cooking oil for 60 days. Resting blood pressure was measured at days 0, 15, 30, 45, and 60, whereas the fasting lipid profile was measured at days 0 and 60. RESULTS: Significant reduction in blood pressure (systolic, diastolic, and mean arterial) from days 0 to 15, 30, 45, and 60 were observed in hypertensives treated with sesame oil blend alone (P < .001), nifedipine alone (P < .001), and combination of sesame oil blend and nifedipine (P < .001). Sesame oil blend with nifedipine-treated group showed greatest reduction in blood pressure. Total cholesterol, low-density lipoprotein cholesterol, triglycerides, and non-high-density lipoprotein cholesterol levels reduced, whereas high-density lipoprotein cholesterol levels increased significantly only in hypertensives treated with sesame oil blend alone and the combination of sesame oil blend and nifedipine (P < .001). CONCLUSION: We demonstrate for the first time that using a blend of sesame oil and rice bran oil as cooking oil showed a significant antihypertensive and lipid-lowering action and had noteworthy additive effect with antihypertensive medication.

A Blend of Sesame and Rice Bran Oils Lowers Hyperglycemia and Improves the Lipids.

BACKGROUND: Considering the health benefits of sesame oil and rice bran oil, the study was conducted to determine the extent to which the daily use of this blend of oils controls hyperglycemia and improves the lipid profile. METHODS: In this 8-week open-label randomized dietary intervention study, 300 type 2 diabetes mellitus patients and 100 normoglycemic subjects were grouped as 1) normoglycemic subjects (n = 100) treated with sesame oil blend Vivo (Adani Wilmar, Ahmedabad, Gujarat, India), 2) type 2 diabetes mellitus patients treated with sesame oil blend (n = 100), 3) type 2 diabetes mellitus patients treated with glibenclamide (n = 100; 5 mg/d), and 4) type 2 diabetes mellitus patients treated in combination of glibenclamide (5 mg/d) and sesame oil blend (n = 100). Twelve-hour fasting blood glucose, glycated hemoglobin (HbA1c), and lipid profile followed by postprandial blood glucose were measured at baseline. Sesame oil blend was supplied to the respective groups, who were instructed to use as cooking oil for 8 weeks. Fasting and postprandial blood glucose was measured at week 4 and week 8, while HbA1c and lipid profile were measured at week 8. RESULTS: At week 4 and week 8, type 2 diabetes mellitus patients treated with sesame oil blend or glibenclamide or combination of glibenclamide and sesame oil blend showed significant reduction of fasting and postprandial blood glucose (P <.001). HbA1c, total cholesterol, triglycerides, low-density lipoprotein cholesterol, and non-high-density lipoprotein cholesterol were significantly reduced (P <.001), while high-density lipoprotein cholesterol was significantly increased at week 8 (P <.001) in type 2 diabetes mellitus patients treated with the sesame oil blend or combination of glibenclamide and sesame oil blend; whereas glibenclamide-alone-treated type 2 diabetes mellitus patients showed a significant reduction of HbA1c (P <.001) only. CONCLUSIONS: A novel blend of 20% cold-pressed unrefined sesame oil and 80% physically refined rice bran oil as cooking oil, lowered hyperglycemia and improved the lipid profile in type 2 diabetes mellitus patients.

Homocysteine-induced oxidative stress upregulates chymase in mouse mastocytoma cells.

Reactive oxygen species (ROS) such as hydrogen peroxide (H(2)O(2)), O(*-)(2) and OH(*) participate in the pathogenesis of ischemia/reperfusion injury, inflammation and atherosclerosis. Our previous studies have suggested that increased angiotensin II (Ang II)-forming chymase may be involved in the development of atherosclerosis. However, the regulatory mechanism of chymase expression has not yet been clarified. In this study, we tested whether oxidative stress upregulates mouse mast cell proteinase chymase, mouse mast cell proteinase (MMCP)-5 or MMCP-4. We also examined the expression and activity of these proteins after treatment. Cultured mouse mastocytoma cells (MMC) displaying chymase-dependent Ang II-forming activity were treated with H(2)O(2) and several aminothiols with or without anti-oxidants. The levels of MMCP-5 and MMCP-4 expression were determined by quantitative RT-PCR; the level of chymase-dependent Ang II-forming activity was measured by high performance liquid chromatography using Ang I as a substrate. Treatment of MMC with homocysteine (0.1-3 mmol l(-1)) significantly increased MMCP-5 and MMCP-4 expression, as well as Ang II-forming activity. These effects were significantly inhibited by the addition of catalase and further suppressed by the combination of catalase and superoxide dismutase. Incubation with hydrogen peroxide alone caused a significant increase in Ang II-forming activity, which was completely suppressed by co-treatment with catalase. Furthermore, MMCP-5 and MMCP-4 expression levels were drastically suppressed and chymase induction by homocysteine was diminished under the GATA-inhibited condition. Homocysteine increased mast cell chymase expression and activity through the mechanism of oxidative stress. Our results suggest that there is a biochemical link between oxidative stress and the local Ang II-forming system.