Abstract P029: Aspartate And Potassium Aspartate May Contribute To A Mechanism By Which Saccharina Japonica Extract Attenuates Hypertension In 2-kidney, 1-clip Renovascular Hypertensive Rats.

Hypertension ◽  
2020 ◽  
Vol 76 (Suppl_1) ◽  
Author(s):  
Yukiko Segawa ◽  
Saki Maruyama ◽  
Hiroko Hashimoto ◽  
Tomoko Osera ◽  
Nobutaka Kurihara

Introduction: Saccharina japonica (SJ) is one of brown algae. The extract of SJ (SJE) is often used for soup stock in Japanese cuisine. We recently observed the decreases in blood pressure (BP) by intake of SJ or SJE diet in 2-kidney, 1-clip renovascular hypertensive (2K1C) rats. SJ is rich in aspartate (Asp), which is the umami taste of amino acid. The intake of Asp was reported to reduce BP in Dahl salt sensitive rats. As well, the potassium Asp (AspK) intake was reported to improve BP in hypertensive patients. 70% (70 of 100) of amino acids such as Asp are eluted into the SJE from SJ. Therefore, we hypothesized that Asp in SJE contributes to the mechanism of BP reduced by dietary SJE in 2K1C rats. In this study, we observed BP in 2K1C rats fed a diet containing Asp or AspK and investigated whether those diets alleviate hypertension to the same extent of the diet containing SJE. Methods: Male Sprague-Dawley rats (6 wks) were treated with sham operation (SHAM) or clipping the left renal artery (2K1C). After surgery, the rats fed a control diet (C), a diet containing Asp, AspK or SJE for 6 weeks. The content of SJE was set to be the same as that in our previous study. The amount of Asp in diet was set to be the same as that in our previous study which showed the antihypertensive effect of SJ. The amount of AspK in diet was set to be equimolar to Asp. The systolic BP (SBP) was measured by a tail-cuff method every week. At the end of the procedure, mean arterial BP (MAP) was measured in each rat under anesthesia. Results: Six weeks after the surgery, 2K1C-C significantly increased in SBP compared with SHAM-C (126±2 vs 159±4 mmHg, p<0.05). However, 2K1C-Asp (138±3), -AspK (142±4), and -SJE (135±4) decreased compared with 2K1C-C (p<0.05) respectively. MAP was significantly higher in 2K1C-C than in SHAM-C (162±3 vs 131±5, p<0.05). It showed a significant decrease in 2K1C-Asp (142±3), -AspK (148±3) and -SJE (144±4), compared with 2K1C-C (p<0.05), respectively. There were no significant differences among 2K1C-Asp, -AspK and -SJE, in either SBP or MAP. Conclusions: Asp and AspK may attenuate hypertension in 2K1C renovascular hypertension as much as SJE which contains similar quantities of Asp. It is possible that Asp and/or AspK eluted into SJE contributes to the mechanism of alleviating hypertension by SJE in 2K1C.

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Saki Maruyama ◽  
Yukiko Segawa ◽  
Hiroko Hashimoto ◽  
Tomoko Osera ◽  
Nobutaka Kurihara

Objective: One of foods indispensable to Japanese cuisine “Washoku” is algae, including Saccharina japonica (SJ) and Undaria pinnatifida. The intake of SJ is reported to decrease blood pressure (BP) in spontaneously hypertensive rats in some studies, and in 2-kidney, 1-clip hypertensive (2K1C) rats in our studies. Since SJ soaked in vinegar is often used in Japanese cuisine, we observed the effects of dietary intake of SJ soaked in vinegar on BP in 2K1C rats. Methods: Male Sprague-Dawley rats (6 wks) were treated with sham operation (SHAM) or clipping the left renal artery (2K1C). After surgery, the rats started receiving a control diet (C), a diet with 5.0% (w/w) SJ (S), or a diet with 5.0% SJ soaked in 5.0% (v/v) vinegar (SV). Systolic BP (SBP) was measured by a tail-cuff method every week for 6 weeks. At the end of the protocol, mean arterial BP (MAP) was measured in each rat under anesthesia. Results and Discussion: Analysis of variance shows that SBP was significantly higher in 2K1C-C than SHAM-C through the experimental period (P<0.001), and that SBP was lower in 2K1C-S (P<0.05) and -SV (P<0.001) than in 2K1C-C (Fig). It also demonstrated that 2K1C-SV provided a significant reduction in SBP compared with 2K1C-S (p<0.001). At the end of the protocol, MAP in 2K1C-C was significantly higher than SHAM-C (154±4 vs 141±4 mmHg, P<0.05). Compared with 2K1C-C, a significant reduction in MAP was observed not in 2K1C-S (143±2 mmHg) but in 2K1C-SV (133±4 mmHg, p<0.05). Soaking in vinegar might bring alginate, which is one of possible components playing an important role in decreasing BP by SJ, to a low molecule and enhance the effect. Conclusion: SJ soaked in vinegar may decrease BP more than SJ in 2K1C rats.


2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Yukiko Segawa ◽  
Hiroko Hashimoto ◽  
Saki Maruyama ◽  
Tomoko Osera ◽  
Nobutaka Kurihara

Objective: Saccharina japonica (SJ), one of brown algae, is cultivated or grows wild in Japan and neighbor countries. The extract “dashi” is used for soup stock in Japan. We reported the decreases in blood pressure (BP) both by the intake of SJ diet and by dashi extracted from SJ (DASHI) in 2-kidney, 1-clip renovascular hypertensive (2K1C) rats. Some researchers have suggested that alginic acid (AA) may be involved in the mechanism of the SJ effect. However, DASHI contains AA as much as 5%(5 of 100) of what the original SJ contains. Thus, the antihypertensive effects by SJ in 2K1C may be through the other contents of SJ. SJ is rich in Glutamic acid (GA) which is one of the umami, the intake of which was reported to decrease BP in human in epidemiologic studies. GA is eluted from the SJ into the DASHI when extracting DASHI from SJ. Therefore, we hypothesized that GA in DASHI contributes to the mechanism of BP decreased by DASHI diet in 2K1C rats. In this study, we observed BP in 2K1C rats fed a diet containing GA as much as that in the SJ diet which had decreased BP in the previous study. Methods: Male Sprague-Dawley rats (6wks) were treated with sham operation (SHAM) or clipping the left renal artery (2K1C). After surgery, the rats started receiving a control diet (C) or a diet containing L-GA (G) for 6 weeks. The systolic BP (SBP) was measured by a tail-cuff method every week. At the end, mean arterial BP (MAP) was measured in each rat under anesthesia. Result: Six weeks after the surgery, SBP was significantly higher in 2K1C-C than in SHAM-C (163±2 vs 111±5 mmHg, p<0.05). In 2K1C-G (171±7), it showed no significant difference compared with 2K1C-C and was significantly higher than that in SHAM-C (p<0.05). At the end of the protocol, MAP showed the similar results to SBP. Conclusion: Glutamic acid may not contribute to the mechanism of alleviating hypertension by dietary SJ and SJ extract in 2K1C.


Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Saki Maruyama ◽  
Yukiko Segawa ◽  
Hiroko Hashimoto ◽  
Tomoko Osea ◽  
Nobutaka Kurihara

Objective: Saccharina japonica (SJ), one of brown algae, is a common foodstuff in Japan and neighbor countries. Some studies have shown that the intake of SJ decreases blood pressure (BP) in spontaneously hypertensive rats. As well, we previously observed it in 2-kidney, 1-clip renovascular hypertensive (2K1C) rats. However, the mechanism is still unclear. One of possible components of SJ which play an important role in decreasing BP is alginate. Since alginate is richer in the roots than in the blades in SJ, in the present study, we compared the effects in alleviating BP of intake of SJ roots with that of SJ blades in 2K1C rats. We also evaluated angiotensin II receptor type 1 (AT1R) mRNA to investigate the role of renin-angiotensin system in the mechanism. Methods: Male Sprague-Dawley rats (6 wks) were treated with sham operation (SHAM) or clipping the left renal artery (2K1C). After surgery, the rats started receiving a control diet (C) or a diet containing 5.0% (w/w) SJ blades (B), or SJ roots (R) for 6 weeks. The systolic BP (SBP) was measured by a tail-cuff method every week. At the end of the protocol, mean arterial pressure (MAP) was measured in each rat under anesthesia. Then, the aortas were removed for extracting mRNA. AT1R-mRNA expression was evaluated using reverse transcriptase quantitative real-time PCR. Results: SBP was significantly higher in 2K1C-C than SHAM-C through the experiment period (p<0.001). SBP in 2K1C-B and -R was significantly lower than in 2K1C-C (p<0.001). 2K1C-B showed a significant reduction in SBP compared with in 2K1C-R (p<0.05). At the end of the protocol, MAP showed the similar trend to SBP. AT1R mRNA expression was higher in 2K1C than in SHAM, but there were no significant differences among 2K1C-C, -B and -R. Conclusion: Although alginate is richer in the roots than in the blades in SJ, the effects in alleviating BP was higher in the blades than in the roots. Thus, alginate may play no major role in the mechanism. AT1R may not play an important role, neither. Therefore, we need investigate other possible mechanisms.


Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Saki Maruyama ◽  
Yukiko Segawa ◽  
Ayaka Harui ◽  
Hiroko Hashimoto ◽  
Tomoko Osera ◽  
...  

Objectives: One of foods used for Japanese cuisine “Washoku” is brown algae, including Saccharina japonica (SJ). The intake of SJ is reported to decrease blood pressure (BP) in spontaneously hypertensive rats in some studies, and in 2-kidney, 1-clip hypertensive (2K1C) rats in our studies. Several studies indicated that dietary fibers contained in SJ, such as alginate and fucoidan, may play an important role in reducing BP. We previously demonstrated that SJ intake did not decrease BP in normotensive rats fed a normal-salt (NS) diet. We also observed that the suppression of BP rise by SJ intake was stronger in 2K1C rats fed a high-salt (HS) diet than in 2K1C rats fed an NS diet. An HS diet may lead to the development of hypertension in both humans and rats. However, to our knowledge, it has not been reported that the effect of SJ intake on BP in normotensive rats fed an HS diet. In this study, we compared the effects of SJ intake on BP between in normotensive and hypertensive rats when fed an HS diet. Methods: Male Sprague Dawley rats (6 wks) were treated with sham operation (SHAM) or clipping the left renal artery (2K1C). After surgery, rats were received a control diet (CTL) or a diet contained 5.0% (5 of 100, w/w) SJ, with an NS (0.7% NaCl) or HS (6.0% NaCl) in diets for 6 weeks. Systolic BP (SBP) was measured by a tail-cuff method every week. At the end of the protocol, mean arterial pressure (MAP) was measured in each rat under anesthesia. Results and Discussion: Analysis of variance showed that SBP was significantly higher in 2K1C-HS-CTL than in SHAM-HS-CTL (P<0.001, 156±4 vs 131±2 mmHg at the 6th week), and that SBP was lower in 2K1C-HS-SJ (146±3 mmHg) than in 2K1C-HS-CTL (P<0.05). On the other hand, there were no significant differences in SBP among SHAM groups. MAP in 2K1C-HS-CTL rats was significantly higher than that in SHAM-HS-CTL rats (153±2 vs 132±4 mmHg, P<0.005). MAP in 2K1C-HS-SJ (140±5 mmHg) rats was significantly lower than that in 2K1C-HS-CTL rats (P<0.05). There were no significant differences in MAP among SHAM groups. These findings suggested that SJ intake has an antihypertensive effect in a hypertensive model of rats, but no effect of lowering BP in a normotensive model of rats, unlike antihypertensive drugs, which reduce BP in both hypertensive and normotensive model.


Hypertension ◽  
2017 ◽  
Vol 70 (suppl_1) ◽  
Author(s):  
Saki Maruyama ◽  
Yukiko Segawa ◽  
Natsumi Saito ◽  
Ayuna Yamaoka ◽  
Hiroko Hashimoto ◽  
...  

Objective: One of foods necessary to Japanese cuisine “Washoku” is algae, including Saccharina japonica (SJ) and Undaria pinnatifida (UP). The intake of SJ was observed to decrease blood pressure (BP) in spontaneously hypertensive rats in some studies, and in 2-kidney, 1-clip hypertensive (2K1C) rats in our studies. Furthermore, we observed the interactive effects of SJ and vinegar on BP in 2K1C rats (Kitamura S et al; Hypertension 2013, Maruyama S et al; Hypertension 2016). In the present study, we investigated the interactive effects of UP sporophyll (UPS) and vinegar, as well as the effect of UPS, on BP in 2K1C rats. We also evaluated angiotensin II type 1 receptor (AT1R) mRNA expression, in the mechanism. Methods: Male Sprague-Dawley rats (6 wks) were treated with sham operation (SHAM) or clipping the left renal artery (2K1C). After surgery, the rats started receiving a control diet (C) or a diet with 5.0% (w/w) UPS, and a tap water or a water containing 5.0% (v/v) rice vinegar (V) for 6 weeks. Systolic BP (SBP) was measured by a tail-cuff method every week. At the end of the protocol, mean arterial pressure (MAP) was measured in each rat under anesthesia. Then, the aortas were removed for extracting mRNA. AT1R mRNA expression was evaluated using real-time RT-PCR. Results: Through the experiment period, SBP was significantly higher in 2K1C-C than in SHAM-C ( P < 0.001). Neither 2K1C-V nor -UPS showed significant differences in SBP from 2K1C-C. However, 2K1C-UPS+V provided a significant reduction in SBP compared with 2K1C-C, -V, and -UPS ( P < 0.01). At the end of the protocol, 2K1C-C was higher in SBP than SHAM-C (166 ± 3 vs 137 ± 3 mmHg, P < 0.001). 2K1C-UPS+V (155 ± 4 mmHg) was tended to be lower than 2K1C-C, -V (162 ± 8 mmHg), and -UPS (164 ± 3 mmHg). Thus, BP was reduced only in 2K1C-UPS+V in 2K1C animals. The observations in MAP were similar to in the SBP. No significant differences in AT1R mRNA expression were observed among SHAM-C (1.3 ± 0.2), 2K1C-C (1.2 ± 0.3), -V (1.0 ± 0.2), -UPS (1.3 ± 0.2) and -UPS+V (1.0 ± 0.2). Conclusion: UPS and vinegar may decrease BP collaboratively in 2K1C rats. AT1R mRNA may not play an important role in the mechanism.


Hypertension ◽  
2017 ◽  
Vol 70 (suppl_1) ◽  
Author(s):  
Ayuna Yamaoka ◽  
Yukiko Segawa ◽  
Saki Maruyama ◽  
Natsumi Saito ◽  
Hiroko Hashimoto ◽  
...  

Objective: Hesperidin (HES) is a flavonoid which is contained in citrus fruit peel. It has physiological effects on blood vessels such as strengthening capillary vessels. Thus, it is known to be one of the effective ingredients of herbal medicine. Some studies have shown that the intake of HES decreases blood pressure (BP) in spontaneously hypertensive rats. The antihypertensive effect of HES is suggested to be due to vasodilation by nitric oxide (NO). However, its mechanism has not been clarified in detail. In this study, we observed whether HES intake decreases BP in 2-kidney, 1-clip renovasucular hypertensive rats (2K1C) and evaluated endothelial NO synthase (eNOS) mRNA to investigate its role in the mechanism. Methods: Male Sprague-Dawley rats (6 weeks old) were treated with sham operation (SHAM) or clipping the left renal artery (2K1C). After surgery, the rats started receiving continuously a control diet (C) or a diet containing 0.1% (w/w) HES for 6 weeks. The systolic BP (SBP) was measured by a tail-cuff method every week. At the end of the protocol, mean arterial blood pressure (MAP) was measured in each rat under anesthesia. Then, the aortas were removed for extracting mRNA. eNOS mRNA expression was evaluated using real-time RT-PCR. Results: At the end of the protocol, SBP in 2K1C-C was significantly higher than in SHAM-C (170±6 vs 117±6 mmHg, p <0.001). On the other hand, 2K1C-HES was lower in SBP (141±4 mmHg) than 2K1C-C ( p <0.01). There were no significant differences between SHAM-HES (122±7 mmHg) and SHAM-C. MAP at the end of the protocol were similar to in SBP. ANOVA revealed mRNA expression of eNOS was significantly higher in 2K1C than in SHAM ( p <0.05), and showed no significant difference between C and HES, nor a significant interaction. Conclusion: Continuous intake of HES may suppress BP increase in 2K1C. The role of eNOS mRNA expression may not be involved in the mechanism.


Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Saori Kitamura ◽  
Hiroko Hashimoto ◽  
Yukiko Segawa ◽  
Nobutaka Kurihara

Objective: Allium bakeri (AB) known as “rakkyo” and Allium sativum known as “garlic” contain alliin. Alliin easily turns into allicin, which is reported to decrease blood pressure (BP) through activating the excitatory ion channel transient receptor potential ankyrin-1. Thus, it is suggested that these vegetable decrease BP. Actually, garlic is reported to decrease BP and aortic media thickness in hypertensive animal models. However, it is practically difficult that garlic shows the effects, because it can hardly be eaten without heating and allicin is thermolabile. On the other hand, AB is usually eaten without heating. Therefore, in this study, we tested whether AB intake alleviates hypertension and aortic media thickness in hypertensive rats. Method: We used 2-kidney, 1-clip (2K1C) renovascular hypertension model. Male Sprague-Dawley rats (6 wo) were treated with sham operation (SHAM) or clipping the left renal artery (2K1C). After surgery, SHAM and 2K1C rats were respectively divided into 2 groups, which received a control diet (CONT) or a diet containing 1.0 % (w/w) freeze-dried AB powder for 7 weeks (AB). The systolic BP (SBP) was measured by a tail-cuff method every week. At the end of the protocol, mean arterial BP (MAP) was measured in each rat under anesthesia. Then, thoracic aorta was removed and the section of aorta was stained with hematoxylin and eosin. Results: From the 2nd week after surgery until the end of the protocol, SBP in 2K1C-CONT went up significantly compared with SHAM-CONT (174 ± 7 vs 120 ± 5 mmHg, at the end of the protocol, P < 0.01). However, SBP in 2K1C-AB did not go up through the protocol (127 ± 7 mmHg, P < 0.01 with 2K1C-CONT, at the end). In addition, the AB diet showed no significant effects on SBP in SHAM. These observations in SBP were similar to in MAP at the end of the protocol. The aortic media thickening was observed in 2K1C-CONT compared with SHAM-CONT. In 2K1C-AB, the thickness was significantly decreased compared with 2K1C-CONT, and was not significantly different from that in SHAM-AB. There were not significant differences between SHAM-CONT and SHAM-AB. Conclusion: Chronic intake of Allium bakeri, which can be eaten without heating, alleviated hypertension and aortic media thickness in rats with renovascular hypertension.


1991 ◽  
Vol 260 (1) ◽  
pp. E95-E100 ◽  
Author(s):  
L. N. Kaufman ◽  
M. M. Peterson ◽  
S. M. Smith

Male Sprague-Dawley rats fed either a high-fat diet or a glucose-enriched diet developed higher blood pressure (BP) than rats fed a control diet. After 8 wk of diet treatment systolic BP was 11% higher (P less than 0.01) in fat-fed rats and 7% higher (P less than 0.05) in glucose-fed rats when compared with rats fed the control diet. Rats fed the high-fat diet developed hypertension only when they were allowed to overeat and become obese and hyperinsulinemic. But when their feeding was restricted to prevent obesity and hyperinsulinemia, they remained normotensive. In contrast, elevated BP developed in rats consuming the glucose diet in the absence of obesity or hyperinsulinemia. After 7 wk of diet treatment, urinary norepinephrine excretion was 1.9 +/- 0.1, 1.9 +/- 0.1, and 1.5 +/- 0.1 micrograms/day in rats fed the high-fat, glucose, and control diets, respectively (P less than 0.05 vs. control). Higher norepinephrine excretion in hypertensive rats suggests that increased sympathetic nervous system (SNS) activity might participate in mediating the effects of dietary fat or glucose on BP. In addition, insulin may contribute to raising BP in rats fed the high-fat diet, either directly or indirectly through its stimulatory effect on the SNS. We conclude that chronic feeding of diets high in fat or glucose increases BP and enhances SNS activity in rats.


2000 ◽  
Vol 279 (4) ◽  
pp. F636-F645 ◽  
Author(s):  
Alicia J. Allred ◽  
Mark C. Chappell ◽  
Carlos M. Ferrario ◽  
Debra I. Diz

The present study determined the effect of either occlusion of the left renal artery for 60 min (ischemia) or sham operation on angiotensin (ANG) receptors and tissue and urinary levels of ANG peptides between 24 and 72 h recovery in male Sprague-Dawley rats. At 24 h postischemia, urinary concentrations of ANG I and ANG-(1–7) rose by an average of 83 and 64%, respectively ( P < 0.05) but had declined to control levels by 72 h. Tissue ANG II rose at 24 h in postischemic kidneys by an average of 63% compared with the contralateral nonischemic kidney ( P < 0.05). Whereas the enzymatic activity of angiotensin-converting enzyme and neprilysin was reduced after ischemia, renal renin activity in ischemic kidneys rose by 74% compared with sham-operated kidneys. Receptor autoradiography using 125I-labeled [Sar1,Thr8]ANG II (125I-Sarthran) (0.8 nM) revealed a decreased apparent density of ANG receptors (>80% AT1) in ischemic kidneys with a trend for a decrease in the contralateral nonischemic kidneys compared with the kidneys from sham-operated rats. Twenty-four hours after ischemia, ANG II receptors decreased by 68% in glomeruli ( P < 0.05), 49% in the outer cortical tubulointerstitial area ( P < 0.05), and 48% in the inner cortical-outer medullary area of the vasa recta ( P < 0.05). Medullary binding decreased ∼50% in both the ischemic kidney and the contralateral nonischemic kidney compared with sham. In all regions of the ischemic kidney, receptors recovered by 72 h to levels not different from sham control rats. The marked change in urinary ANG I and ANG-(1–7) at 24 h following occlusion indicates these peptides may be potential urinary markers for acute renal ischemia. The reduction of receptors in vascular and tubular regions of the ischemic kidney provides a mechanism for the loss of vasoconstrictor responses to ANG II following ischemia previously reported by others.


1998 ◽  
Vol 95 (4) ◽  
pp. 445-451 ◽  
Author(s):  
Rachel OKUNIEWSKI ◽  
Elizabeth A. DAVIS ◽  
Bevyn JARROTT ◽  
Robert E. WIDDOP

1.The objective of this study was to determine the influence of gender on the development of renal hypertension in Sprague–Dawley rats using the Goldblatt two-kidney, one-clip (2K1C) model. In addition, this study examined the effect of ovariectomy upon the development of hypertension in female rats. 2.At 10 weeks of age, male, intact female and ovariectomized female rats underwent clipping of the right renal artery or sham operation. Tail-cuff plethysmography was used to monitor the systolic blood pressure of all animals for 7 weeks post-clipping or sham operation. Rats were sub-grouped according to whether or not they developed hypertension (systolic blood pressure ⩾ 150 ;mmHg). 3.Within 2 to 3 weeks of clipping, hypertension was induced in only 53% (n = 120) of the intact female 2K1C rats, but in 83% (n = 18) of the male and 78% (n = 18) of the ovariectomized female rats. 4.Seven weeks after right renal artery clipping, plasma renin activity was determined in a subset of each group and was found to be 5–6 fold higher in male (17.29±4.04 ;ng angiotensin I·h-1·ml-1) and ovariectomized female (9.71±1.25 ;ng angiotensin I·h-1·ml-1) hypertensive rats compared with their respective normotensive or sham-operated counterparts (3.39±0.58 ;ng angiotensin I·h-1·ml-1 and 1.60±0.41 ;ng angiotensin I·h-1·ml-1 respectively) (P< 0.05, analysis of variance). In contrast, the plasma renin activity measured in intact female hypertensive rats was not significantly different from that measured in the corresponding 2K1C normotensive or sham-operated groups. 5.These results indicate that the success rate of inducing renal hypertension in Sprague–Dawley rats is higher in males than in intact females. Furthermore, these results suggest that the induction of 2K1C hypertension may be influenced by ovarian hormones.


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