High blood pressure-lowering and vasoprotective effects of milk products in experimental hypertension

Milk casein-derived angiotensin-converting enzyme (ACE)-inhibitory tripeptides isoleucine-proline-proline (Ile-Pro-Pro) and valine-proline-proline (Val-Pro-Pro) have been shown to have antihypertensive effects in human subjects and to attenuate the development of hypertension in experimental models. The aim of the present study was to investigate the effect of a fermented milk product containing Ile-Pro-Pro and Val-Pro-Pro and plant sterols on already established hypertension, endothelial dysfunction and aortic gene expression. Male spontaneously hypertensive rats (SHR) with baseline systolic blood pressure (SBP) of 195 mmHg were given either active milk (tripeptides and plant sterols), milk or water ad libitum for 6 weeks. SBP was measured weekly by the tail-cuff method. The endothelial function of mesenteric arteries was investigated at the end of the study. Aortas were collected for DNA microarray study (Affymetrix Rat Gene 1.0 ST Array). The main finding was that active milk decreased SBP by 16 mmHg compared with water (178 (SEM 3) v. 195 (SEM 3) mmHg; P < 0.001). Milk also had an antihypertensive effect. Active milk improved mesenteric artery endothelial dysfunction by NO-dependent and endothelium-derived hyperpolarising factor-dependent mechanisms. Treatment with active milk caused mild changes in aortic gene expression; twenty-seven genes were up-regulated and eighty-two down-regulated. Using the criteria for fold change (fc) < 0.833 or > 1.2 and P < 0.05, the most affected (down-regulated) signalling pathways were hedgehog, chemokine and leucocyte transendothelial migration pathways. ACE expression was also slightly decreased (fc 0.86; P = 0.047). In conclusion, long-term treatment with fermented milk enriched with tripeptides and plant sterols decreases SBP, improves endothelial dysfunction and affects signalling pathways related to inflammatory responses in SHR.     

牛乳酪蛋白酶解物对SHR大鼠血压影响的试验研究

目的:研究牛乳酪蛋白酶解物对自发性高血压大鼠(SHR)的抗高血压作用。方法:将SHR和Wistar大鼠按照不同试验要求分组,单次灌胃和连续灌胃后,测定血压和组织内的血管紧张素转换酶(ACE)活性。结果:单次灌胃高剂量的酪蛋白酶解物可使SHR的血压在5～7h显著降低,在24h又恢复到起始值,而Wistar大鼠血压无变化。以不同剂量连续4w灌胃SHR,在3～4w时其血压显著降低。SHR中动脉组织的ACE活性显著降低,其它器官组织的ACE活性差异不显著。结论:牛乳酪蛋白酶解物对SHR具有降压作用,其降压效果与剂量之间有相关性。     

Short-term effect of egg-white hydrolysate products on the arterial blood pressure of hypertensive rats

In the present study we evaluate the blood pressure-lowering effect of the following products: the hydrolysate obtained from egg white (EW) by enzymatic treatment with pepsin (HEW), the peptide fraction of HEW with molecular mass lower than 3000 Da (HEW<3000 Da), and three peptide sequences isolated from HEW<3000 Da (Tyr-Ala-Glu-Glu-Arg-Tyr-Pro-Ile-Leu: YAEERYPIL); (Arg-Ala-Asp-His-Pro-Phe-Leu: RADHPFL); and (Ile-Val-Phe (IVF)). These peptides, and also HEW and HEW<3000 Da, had been characterized previously in vitro as potent inhibitors of angiotensin-converting enzyme (ACE). EW and the products mentioned earlier were orally administered by gastric intubation, to 17-20-week-old male spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. We measured the systolic blood pressure (SBP) and the diastolic blood pressure (DBP) of the rats by the tail cuff method before administration and also 2, 4, 6, 8 and 24 h post-administration. Distilled water served as negative control, and we used captopril (50 mg/kg) as positive control to carry out similar experiments with a known ACE inhibitor. HEW, HEW<3000 Da and the three peptide sequences decreased SBP and DBP in SHR but they did not modify these variables in WKY rats. The peptide sequences YAEERYPIL, RADHPFL and IVF showed a potency to decrease blood pressure greater than HEW or HEW<3000 Da. The results obtained suggest that the studied products could be used as a functional food with potential therapeutic benefit in the prevention and treatment of hypertension.     

Effects of Val-Pro-Pro and Ile-Pro-Pro on nondipper patients: a preliminary study

Much clinical evidence on the antihypertensive effects of the milk-derived antihypertensive peptides Val-Pro-Pro and Ile-Pro-Pro (lactotripeptides) has been reported. However, circadian rhythm effects determined by ambulatory blood pressure monitoring (ABPM) to eliminate the confounding influence of the white-coat effect have not been fully studied. Twelve hypertensive patients not receiving antihypertensive medication (2 men, 10 women; mean age±standard deviation, 63.5±8.3 years) who had been visiting our clinic for more than 1 year participated in this study. Mean (±standard deviation) systolic blood pressure (SBP) and diastolic blood pressure (DBP) were 142.4±2.6 and 83.5±6.4?mm Hg, respectively, at the first office visit. After patients ingested a fermented milk product containing antihypertensive peptides (2.53?mg Val-Pro-Pro; 1.52?mg Ile-Pro-Pro) for more than 4 weeks, both office SBP and DBP were significantly reduced to a mean (±standard deviation) of 133.3±7.0?mm Hg and 76.5±8.4?mm Hg (P<.001 and P<.005 by paired t-test), respectively. The 24-hour SBP and DBP determined by ABPM were reduced from 127.3±2.4 and 78.7±2.3?mm Hg to 120.2±2.4 and 75.0±2.2?mm Hg (P<.001 and P<.05), respectively. Awake-time SBP (08:00-21:00), night-time SBP (0:00-05:00), and early-morning SBP (06:00-07:00) were reduced from 130.9±2.4 to 123.3±2.3?mm Hg, 118.7±2.9 to 113.2±3.4?mm Hg, and 132.8±4.3 to 122.4±3.9?mm Hg (by paired t-test: P<.001, P<.05, and P<.05), respectively. As seen with DBP measured by ABPM, 24-hour DBP and awake-time DBP were significantly reduced from 78.7±2.3 to 75.0±2.2?mm Hg and 82.1±2.5 to 77.3±2.2?mm Hg (P<.05 and P<.01), respectively. Office BP and 24-hour blood pressure did not significantly differ between the dipper and nondipper groups at baseline. However, after treatment, night-time and early-morning blood pressure were significantly reduced from baseline in the nondipper group (-8.5±2.5 and -15.6±3.7?mm Hg; P<.05 and P<.01, respectively) but not in the dipper group (-2.5±3.6 and -1.2±4.7?mm Hg; P not significant), and the reduction in early-morning blood pressure significantly differed between the groups (P<.05). These results suggest that Val-Pro-Pro and Ile-Pro-Pro decrease blood pressure in patients with stage I hypertension and result not only in lower blood pressure at night-time but also in lower early-morning SBP in nondipper patients.     

Effect of enzymatically modified isoquercitrin in spontaneously hypertensive rats

Enzymatically modified isoquercitrin (EMIQ) is a water-soluble glycoside of quercetin produced from rutin by enzymatic treatment. We investigated the anti-hypertensive effect of orally administered EMIQ in spontaneously hypertensive rats (SHR). The systolic blood pressure (SBP) in SHR administered EMIQ at a dose of 3 and 26 mg/kg/d was significantly lower than that in the control group on d 22, 36 and 50 of administration. The effect of EMIQ (26 mg/kg/d) was higher than equimolar administration of quercetin. Diltiazem administered as a positive control also suppressed the increase in SBP. and the effect was stronger than that of EMIQ. In the control group, the mean values of mean blood pressure (MBP) and diastolic blood pressure (DBP) were increased after the start of administration. Although diltiazem suppressed the increase in MBP, no significant changes were observed in the EMIQ groups. Compared with the control group, EMIQ groups showed the incidental changes of MBP and heart rate on day 22 of administration only. These results indicate that EMIQ suppressed the increase in SBP in SHR dose-dependently, and was more effective than the aglycone quercetin. It was also speculated that EMIQ showed higher anti-hypertensive effect than quercetin due to the high bioavailability, and the mechanism of SBP suppression is possibly through the improvement of endothelial NO production. In conclusion, our results suggest that EMIQ shows possibility as a naturally-derived safe food material which has an antihypertensive effect.     

Antihypertensive peptides derived from egg proteins

There have been studies of antihypertensive peptides derived from food proteins, but very few described the production of bioactive peptides from egg proteins. The first 2 antihypertensive peptides isolated in egg were obtained by enzymatic hydrolysis of ovalbumin. They correspond to the sequences Phe-Arg-Ala-Asp-His-Pro-Phe-Leu (ovokinin) and Arg-Ala-Asp-His-Phe-Leu (ovokinin 2-7). Both exhibited endothelium-dependent vasodilatory activity. Ovokinin (2-7) had higher antihypertensive potency than ovokinin in spontaneously hypertensive rats (SHR). Modifications in the sequence of ovokinin (2-7) improved the bioavailability of this peptide. It was also demonstrated that different ovalbumin hydrolysates can inhibit angiotensin I-converting enzyme (ACE). We recently obtained an egg white hydrolysate that inhibited the enzyme in vitro. It was obtained by treating egg white with pepsin and it exhibited antihypertensive activity in SHR. Some ACE-inhibitory peptides obtained from this hydrolysate (Tyr-Arg-Glu-Glu-Arg-Tyr-Pro-Ile-Leu, Arg-Ala-Asp-His-Pro-Phe-Leu, and Ile-Val-Phe) also showed antihypertensive activity in these rats. The egg products mentioned could be used as functional food ingredients with potential therapeutic benefit in the prevention and treatment of hypertension.     

Effect of Powdered Fermented Milk with Lactobacillus helveticus on Subjects with High-Normal Blood Pressure or Mild Hypertension

Objective: Two tripeptides (Val-Pro-Pro and Ile-Pro-Pro) that have inhibitory activities for angiotensin I-converting enzyme are produced in milk fermented with Lactobacillus helveticus. In this study we evaluated the effect and safety of powdered fermented milk with L. helveticus CM4 on subjects with high-normal blood pressure or mild hypertension.

Methods: A randomized, placebo-controlled, double-blind study was conducted using 40 subjects with high-normal blood pressure (HN group) and 40 subjects with mild hypertension (MH group). Each subject ingested 6 test tablets (12 g) containing powdered fermented milk with L. helveticus CM4 daily for 4 weeks (test group) or the same amount of placebo tablets for 4 weeks (placebo group).

Results: During treatment, the decrease in systolic blood pressure (SBP) and diastolic blood pressure (DBP) in the test group tended to be greater than in the placebo group for both blood pressure groups. At the end of treatment (week 4), a significant decrease in DBP in the HN group was observed (i.e. 5.0 mm Hg (0.1, 9.9; p = 0.04) compared with the placebo group). There was no significant change in SBP (3.2 mm Hg (95% CI ?2.6, 8.9; p = 0.27). In the MH group, SBP decreased by 11.2 mm Hg (4.0, 18.4; p = 0.003) and there was a statistically non-significant decrease in DBP of 6.5 mm Hg (?0.1, 13.0; p = 0.055) compared with the placebo group. No marked changes were observed in other indexes, including pulse rate, body weight and blood serum variables, and no adverse effects attributed to the treatment was found in each group.

Conclusions: Daily ingestion of the tablets containing powdered fermented milk with L. helveticus CM4 in subjects with high-normal blood pressure or mild hypertension reduces elevated blood pressure without any adverse effects.     

芹菜素对自发性高血压大鼠的降压作用及对肾脏血管紧张素转化酶2表达的影响

目的探讨自发性高血压大鼠(SHR)肾脏血管紧张素转换酶2(ACE2)的表达,了解芹菜素对大鼠肾脏ACE2mRNA表达的影响,观察芹菜素的降压效果。方法 60只雄性SHR大鼠随机分为6组,每组10只:正常对照组、卡托普利阳性对照组以及0.007、0.026、0.104和0.417g/kg芹菜素剂量组。4周后,用荧光实时定量PCR法检测肾脏ACE2mRNA表达,免疫组化法检测肾脏ACE2表达。结果自灌胃第3周开始,卡托普利阳性对照组、0.026、0.104、0.417g/kg芹菜素剂量组的血压均显著低于对照组(P<0.05)。各剂量组大鼠心率、体重与对照组比较差异均无显著性(P>0.05)。给予芹菜素4周后,阳性对照和芹菜素高剂量组ACE2mRNA表达量明显升高(P<0.05)。免疫组化所见ACE2表达情况与mRNA表达水平基本类似。结论芹菜素降低SHR大鼠血压与增强ACE2表达有关。     

瑞士乳杆菌TUST005发酵乳对先天性高血压大鼠血压和心率影响

目的研究瑞士乳杆菌TUST005发酵乳对8w龄先天性高血压大鼠的尾部动脉血压和心率可能产生的影响。方法将雄性原发性高血压大鼠,随机分为5组,每组8只,分别用发酵乳及乳清、水、脱脂乳和普通酸奶,每天灌胃1次,每一试验样品实验期为3d,剂量逐渐升高。用ZH-HX-Z鼠尾无创动脉测量仪测定收缩压和心率。结果当瑞士乳杆菌TUST005发酵乳剂量1.5ml与乳清剂量为2ml,血压的下降和上升速度相对缓慢,维持最低血压水平时间较长分别为4h和6h,降压效果最好且降压值为20.5mmHg。当瑞士乳杆菌TUST005发酵乳乳清剂量为1ml,心率下降幅度为50bpm。结论用瑞士乳杆菌发酵乳喂养SHR大鼠,能明显降低血压和心率。     

Effect of a gamma-aminobutyric acid-enriched dairy product on the blood pressure of spontaneously hypertensive and normotensive Wistar-Kyoto rats

We investigated the blood-pressure-lowering effects of gamma-aminobutyric acid (GABA) and a GABA-enriched fermented milk product (FMG) by low-dose oral administration to spontaneously hypertensive (SHR/Izm) and normotensive Wistar-Kyoto (WKY/Izm) rats. FMG was a non-fat fermented milk product produced by lactic acid bacteria, and the GABA contained in FMG was made from the protein of the milk during fermentation. A single oral dose of GABA or FMG (5 ml/kg; 0.5 mg GABA/kg) significantly (P<0.05) decreased the blood pressure of SHR/Izm from 4 to 8 h after administration, but did not increase that of WKY/Izm rats. The hypotensive activity of GABA was dose-dependent from 0.05 to 5.00 mg/kg in SHR/Izm. During the chronic administration of experimental diets to SHR/Izm, a significantly slower increase in blood pressure with respect to the control group was observed at 1 or 2 weeks after the start of feeding with the GABA or FMG diet respectively (P<0.05) and this difference was maintained throughout the period of feeding. The time profile of blood-pressure change due to administration of FMG was similar to that of GABA. FMG did not inhibit angiotensin 1-converting enzyme. Furthermore, an FMG peptide-containing fraction from reverse-phase chromatography lacked a hypotensive effect in SHR/Izm rats. The present results suggest that low-dose oral GABA has a hypotensive effect in SHR/Izm and that the hypotensive effect of FMG is due to GABA.     

Effects of vitamin C on high blood pressure induced by salt in spontaneously hypertensive rats

By breeding and feeding salt to spontaneously hypertensive rats (SHR) continuously over a long period (until 60 wk old), rats with systolic blood pressures (SBP) of over 270 mmHg were prepared. It was studied whether or not supplying large amounts of vitamin C (200 mg/rat/d) over this period might bring any beneficial effect to blood pressure. Moreover, physico-chemical studies were performed to measure the components and enzymes in the blood and urine at 53 and 60 wk-old, and biochemical studies on vitamin C were also carried out in this experiment. Male (14 rats: 7 wk-old, 100-105 g) and female (15 rats: 7 wk-old, 95-100 g) SHR were divided into three groups and bred continuously for 53 wk. The A group rats were given salt (2.5 g/100 g of diet), the B group rats were given salt and vitamin C (500 mg/100 mL of drinking water), and the C group rats were controls. The results showed almost the same tendencies between male and female rats. The body weights of the SHR in groups A and B were slightly lower than group C. The amount of food intake in groups A and B was almost the same as group C. The amount of water intake was, in the order from highest to lowest, group A, B and C. The SBP of group A rats exhibited the highest value among the three groups. The SBP of group B rats given vitamin C simultaneously with the salt resulted in a low blood pressure level close to that of the controls (group C). Furthermore, the DBP (diastolic blood pressure) also reflected the antihypertensive effect of vitamin C as well. The heartbeat of the rats was highest in group A, and was comparable to the value in the rats receiving vitamin C simultaneously with salt. For the tests on occult blood and protein in the urine, group A rats showed strong positive reactions, whereas the group B and C rats had decreased results for both tests. The organ weights of the liver, stomach, spleen, adrenal gland and kidneys per 100 g rat body weight were not different among the three groups. The values for the bilirubin content, and the enzyme activities of ALT and AST in the blood showed to be the highest in the male rats of group A. The values from the group B rats decreased near to the normal value like the control group. Vitamin C was found to decrease the blood pressure in SHR, and also to work effectively to protect liver and kidney functions even under the condition of very high blood pressure, as high as 250 mmHg.     

天麻钩藤饮、温胆汤和血府逐瘀汤对SHR血压及左室肥厚的影响

目的观察天麻钩藤饮、温胆汤和血府逐瘀汤对自发性高血压大鼠(SHR)血压及左室肥厚的影响。方法 16周龄SHR大鼠40只,随机分为5组:SHR对照组、卡托普利组、天麻钩藤饮组、温胆汤组和血府逐瘀汤组,每组8只,正常对照组WKY大鼠8只;连续干预治疗8周,然后观察三方的降压作用以及对左室肥厚的影响。结果 8周干预治疗后,各治疗组均有降压作用,但天麻钩藤饮组、温胆汤组和血府逐瘀汤组与卡托普利组比较仍有显著差异(p<0.01);卡托普利、天麻钩藤饮、温胆汤和血府逐瘀汤均能显著降低LVM/BW水平,且与SHR对照组相比有显著性差异(p<0.01);治疗组间比较,天麻钩藤饮组、温胆汤组与卡托普利组相比无显著性差异(p>0.05),血府逐瘀汤组优于天麻钩藤饮组、温胆汤组与卡托普利组(p<0.01)。结论天麻钩藤饮、温胆汤和血府逐瘀汤对稳定血压有一定的作用,但与卡托普利的降压作用仍有差距。天麻钩藤饮、温胆汤和血府逐瘀汤有显著逆转左室肥厚的作用;天麻钩藤饮、温胆汤与卡托普利效果相当,血府逐瘀汤优于天麻钩藤饮、温胆汤及卡托普利。     

Plant sterols and casein-derived tripeptides attenuate blood pressure increase in spontaneously hypertensive rats

In this study, we investigated the synergistic effects of plant sterols (PS) and casein-derived tripeptides on arterial tone and blood pressure in experimental hypertension. We hypothesized that PS and tripeptides could have positive, synergistic effects on the development of hypertension and endothelial dysfunction in young spontaneously hypertensive rats (SHR). Six-week-old male SHR were divided into 3 groups to receive milk products containing PS, or PS with tripeptides, or a control containing no active components for 8 weeks. Systolic blood pressure (SBP) was measured weekly, and vascular reactivity measurements with isolated mesenteric arteries were performed at the end of the study. Biochemical measurements for several parameters were performed by enzyme-linked immunosorbent assay using plasma samples. Levels of angiotensin-converting enzyme 1, cyclooxygenase-2, endothelial nitric oxide synthase, and P-selectin messenger RNA expressions were determined from aortic tissue by real-time polymerase chain reaction. The study showed that long-term treatment with PS + tripeptides attenuated the development of hypertension in SHR (SBP, 187 ± 5 mm Hg vs 169 ± 4 mm Hg in control group; P < .01). Plant sterols alone did not affect SBP significantly. Endothelial dysfunction was observed in all SHR; however, treatment with PS resulted in poorer endothelium-dependent and nitric oxide–mediated relaxation compared with other groups. Aortic cyclooxygenase-2 and P-selectin were significantly down-regulated in PS and PS + tripeptides groups when compared with the control group. The expression of endothelial nitric oxide synthase was significantly lower in PS than in PS + tripeptides group. In conclusion, long-term treatment with PS has a slight but not significant antihypertensive effect. Plant sterols do not provide any beneficial effects on endothelial function in hypertensive rats; however, treatment with both PS and tripeptides showed mild anti-inflammatory effects.     

A prospective study of blood pressure and risk of cataract in men

PURPOSE: Cataract is the leading cause of blindness worldwide. Blood pressure has been identified as a risk factor in some, but not all, previous studies. We aimed to test prospectively the hypothesis that high blood pressure increases risk of age-related cataract. METHODS: Participants in the Physicians' Health Study of 22,071 men aged 40 to 84 years in 1982 completed annual questionnaires that provided medical history including self-reported blood pressure, treatment for hypertension, and cataract. Over 12 years, 1392 cataracts were confirmed by medical record review among 17,762 physicians with complete data and no reported cataract at baseline. We used proportional hazards regression models to examine relations of systolic blood pressure (SBP), diastolic blood pressure (DBP), hypertension, as well as antihypertensive medications with cataract, after control for potential confounding factors. RESULTS: In models adjusting for age and randomized treatment assignment, there was a significant relationship of SBP, but not DBP, hypertension, or antihypertensive medications (each p > or = 0.23) with incident cataract. Estimates were attenuated after adjusting for multiple potential confounders, although the relationship of SBP with incident cataract remained significant. The multivariate adjusted rate ratio (95% confidence interval) of cataract for SBP > or = 150 versus < 120 mm Hg was 1.31 (1.04-1.66), p for trend = 0.04. For DBP > or = 90 versus < 70 mm Hg, the estimate was 1.11 (0.84-1.45), p for trend = 0.33.CONCLUSIONS: Overall, these data suggest that the relationship of blood pressure with cataract is not strong, and is subject to confounding by other risk factors. The modest magnitude of the association with SBP and lack of significant relationships with DBP and hypertension may suggest a non-causal relationship of blood pressure with cataract.     

A comparison of the effect of oral captopril and nicardipine in hypertensive crisis

BACKGROUND: Hypertensive crisis is defined as a severe elevation in blood pressure (BP) without target organ injury. There are few data about the efficacy and safety of comparative oral antihypertensive drugs. AIM: To compare the efficacy and safety of oral captopril (25 mg) and nicardipine (20 mg) in hypertensive crisis. METHODS: This prospective, randomized study included 50 patients attended at the emergency department with a hypertensive crisis (arterial blood pressure of at least 180/110 mmHg without target organ damage confirmed after 15 min of rest. Systolic (SBP) and diastolic blood pressure (DBP) and heart rate (HR) were assessed at several intervals during 4 h after the drug administration. Therapeutic success was defined by a SBP< or =160 and DBP< or =90 mmHg two hours after drug administration. The initial clinical characteristics as age, sex, initial systolic and diastolic BP and HR were no different in the two groups. RESULTS: BP levels started to significantly decrease within 15 minutes. At 2 hours, SBP and DBP dropped were similar in captopril group and nicardipine group,respectively to 162/94 vs 161/89 mmHg; p=ns. The therapeutic success at the second hour has been obtained in 68% of cases in the two groups. Age >70 years was a predictor's factor of therapeutic failure in the captopril group. Heart rate significantly dropped after 30 min in the captopril group (82.3 +/- 11.8 vs 77.6 +/- 12.7 c/min; p=0.037). This effect was maintained over four hours. There were no side effects in this study. CONCLUSION: Oral captopril or nicardipine are efficacy and safe in the treatment of hypertensive crisis.     

Sesame Oil Therapeutically Ameliorates Cardiac Hypertrophy by Regulating Hypokalemia in Hypertensive Rats

Background: Hypokalemia and hypertension are common manifestations of preclinical cardiovascular conditions that have a predictive value for cardiovascular morbidity and mortality. Cardiac hypertrophy, an important risk factor in heart failure, is attributed to long‐term hypokalemia and hypertension. Sesame oil is rich in nutrients and possesses potent antihypertensive activities. Methods: We investigated the therapeutic potential of sesame oil using a hypertensive model created by subcutaneously injecting deoxycorticosterone acetate (DOCA; 15 mg/mL/kg in mineral oil; twice weekly for 5 weeks) and supplementing with 1% sodium chloride drinking water (DOCA/salt) to uninephrectomized rats. Sesame oil was administered by oral gavage (0.5 or 1 mL/kg/d for 7 days) after 4 weeks of DOCA/salt treatment. Systolic blood pressure (SBP) and diastolic blood pressure (DBP), electrocardiography (ECG), and K⁺ and Mg²⁺ levels were assessed 24 hours after the last dose of sesame oil. Heart tissue was collected for histologic analysis. Results: Sesame oil effectively reduced the SBP/DBP and ECG abnormalities and increased the serum levels of K⁺ and Mg²⁺ while limiting the urinary excretion of K⁺ in DOCA/salt‐induced hypertensive rats. In addition, sesame oil decreased the heart mass, the thickness of the left ventricle, and the diameter of cardiomyocytes, indicating the regression of left ventricular hypertrophy in the hypertensive rats. Conclusion: We demonstrate that sesame oil therapeutically ameliorates cardiac hypertrophy by regulating hypokalemia in hypertensive rats.     

Predictors of the development of hypertension: ten-year follow-up study in a community]

Predictors of the development of hypertension were examined in a 10-year follow-up study of normotensive Japanese adults. Subjects (n = 265), aged 30-69 years at entry, normotensive and with no past history of antihypertensive treatment at entry, were studied in terms of the relationship of various physical, biochemical, dietary, and lifestyle data to the subsequent development of hypertension (defined as systolic blood pressure (SBP) more than 140 mmHg and/or diastolic blood pressure (DBP) more than 90 mmHg and/or starting antihypertensive treatment) with analysis accomplished using univariate and multivariate life table methods. Univariate analyses by the generalized Wilcoxon test showed significantly higher incidence of hypertension in those subjects with SBP 120 mmHg or more (p < 0.001), DBP 75 mmHg or more (p < 0.001), serum glutamate oxaloacetate transaminase (GOT) 20 KU or more (p < 0.001), serum glutamate pyruvate transaminase (GPT) 15 KU or more (p < 0.001), serum gamma-glutamyl transpeptidase (gamma-GTP) 10 IU/l or more (p < 0.001), age 50 or older (p = 0.002), body mass index 22 kg/m2 or more (p = 0.012), and serum creatinine less than 1.2 mg/dl (p = 0.020) than in the other subjects. Multivariate analysis by the Cox proportional hazards model confirmed that relatively higher SBP (p < 0.001), lower serum creatinine (p < 0.001), higher gamma-GTP (p = 0.002), and higher age (p = 0.041) were independent and significant predictors of future hypertension.     

ACE inhibitor-based treatment and antihypertensive effects in patients with type 2 diabetes

AIM: The presence of hypertension significantly increases cardiovascular risk in diabetic patients. Different classes of antihypertensive drugs, by targeting different pathophysiological mechanisms and therapeutic targets, might provide different antihypertensive effects. The authors speculated that drugs specifically targeting the renin-angiotensin-aldosterone system provide better antihypertensive control than other therapeutic agents. METHODS: Fifty consecutive type 2 diabetic patients with hypertension (M:F 29:21) were followed for 3-9 yrs. Antihypertensive treatment was stable for the last 12 months and included angiotensin convertying enzyme (ACE) inhibitors (ACEI) alone in 8 patients (group IA), ACEI combined with other drugs in 11 patients (group IB) and non-ACEI treatment in 31 patients (group II), 23 of whom were treated with Ca-channel blockers and 8 were treated with beta-blockers alone or with diuretics. During the last month of the study a 3-7 days antihypertensive drugs wash-out was performed. Measurements were performed in sitting position in the same ambulatory conditions, in supine position after 20 min of absolute rest, and in motionless standing station after quickly rising up from sitting rest. RESULTS: Groups IA, IB, and II had similar blood pressure values during antihypertensive therapy within the last year. However, blood pressure values after antihypertensive drug wash-out were significantly higher in groups IA and IB vs. group II (SBP and DBP resting sitting position, P=0.039 and P=0.014 respectively; SBP and DBP in standing position, P=0.001 and P=0.016, respectively). CONCLUSION: These data show that the underlying condition in terms of pathophysiologic mechanisms is more severe in groups IA and IB, including a greater increase of peripheral resistance. Thus we may conclude that the antihypertensive effect of ACEI is greater than other classes of antihypertensive drugs.     

酪蛋白酶解产物对高血压影响的研究

目的:研究酪蛋白酶解产物(casein hydrolysate,CH)对高血压的影响。方法:酪蛋白酶解产物经过大孔树脂DA201C脱盐处理,检测了脱盐酶解产物对血管紧张素转化酶(ACE)的抑制活性和用水解物500、1000mg/kg灌胃,观察SHR大鼠血压的影响。结果:酶解产物对ACE的活性有很强的抑制作用,抑制率为80.1%;低剂量(500mg/kg)组对自发性高血压大鼠(SHR)有显著的降血压作用;高剂量(1000mg/kg)组非常显著。结论:酪蛋白酶解产物具有降血压功能。     

Effect of casein, casein phosphopeptides and calcium intake on ileal 45Ca disappearance and temporal systolic blood pressure in spontaneously hypertensive rats.

Paracellular 45Ca absorption and temporal systolic blood pressure (SBP) measurements were recorded in spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats fed on casein (C) and soya-bean-protein isolate (S) diets, containing 20 (H), 5 (H) and 0.5 (L) g Ca/kg. Similar measurements were also taken in SHR rats only fed on C-M and S-M diets supplemented with 30 g caseinophosphopeptides (CPP)/kg. Absorption of 45Ca from the ileal loop was equivalent in both SHR and WKY animals and largely affected by the level of dietary Ca. In addition, animals fed on C diets exhibited significantly (P < 0.05) greater ileal absorption of 45Ca compared with S-fed animals. This result was attributed to the presence of CPP and a greater (P < 0.05) proportion of soluble 45Ca in the contents of the ileum. Animals fed on S diets supplemented with CPP confirmed this finding. The SBP of SHR rats was higher (P < 0.01) than WKY controls after 9-10 weeks of age. The temporal pattern of observed hypertension was independent of dietary influence in the SHR. The severity of hypertension in SHR rats was affected only by dietary Ca deficiency, and not by Ca supplementation or CPP enhancement of Ca bioavailability. These findings suggest that tryptic digestion products of casein in milk can enhance Ca bioavailability by increasing Ca solubility; however, this action had no effect in reducing hypertension in SHR.