Capsaicin improves hypertension and cardiac hypertrophy via SIRT1/NF-κB/MAPKs pathway in the hypothalamic paraventricular nucleus.

BACKGROUND: Hypertension has seriously affected a large part of the adult and elderly population. The complications caused by hypertension are important risk factors for cardiovascular disease accidents. Capsaicin, a pungent component of chili pepper has been revealed to improve hypertension. However, its potential mechanism in improving hypertension remains to be explored. PURPOSE: In the present study, we aimed to investigate whether capsaicin could attenuate the SIRT1/NF-κB/MAPKs pathway in the paraventricular nucleus of hypothalamus (PVN). METHODS: We used spontaneous hypertensive rats (SHRs) as animal model rats. Micro osmotic pump was used to give capsaicin through PVN for 28 days, starting from age12-week-old. RESULTS: The results showed that capsaicin significantly reduced blood pressure from the 16th day of infusion onward. At the end of the experimental period, we measured cardiac hypertrophy index and the heart rate (HR), and the results showed that the cardiac hypertrophy and heart rate of rats was significantly improved upon capsaicin chronic infusion. Norepinephrine (NE) and epinephrine (EPI) in plasma of SHRs treated with capsaicin were also decreased. Additionally, capsaicin increased the protein expression and number of positive cells of SIRT1 and the 67-kDa isoform of glutamate decarboxylase (GAD67), decreased the production of reactive oxygen species (ROS), number of positive cells of NOX2, those of Angiotensin Converting Enzyme (ACE) and p-IKKß, tyrosine hydroxylase (TH), the gene expression levels of NOX4 and pro-inflammatory cytokines. Capsaicin also decreased the relative protein expressions of protein in MAPKs pathway. CONCLUSION: Current data indicated that capsaicin within the PVN improves hypertension and cardiac hypertrophy via SIRT1/NF-κB/MAPKs pathway in the PVN of SHRs, supporting its potential as candidate drug for preventing and improving hypertension.

[Effects of temperature and phosphorus application on wheat growth at seedling stage and phosphorus form in calcareous fluvo-aquic soil]. / 温度和施磷对石灰性潮土小麦苗期生长及磷形态的影响.

The effects of temperature and phosphate fertilizer application on wheat seedling growth and soil inorganic phosphorus transformation in calcareous fluvo-aquic soil were examined in a pot experiment. The results showed that temperature and phosphorus were important factors affecting wheat growth but without significant interaction. The effect of temperature on wheat growth was greater than that of phosphate fertilizer, and 15 ℃ was the suitable temperature for wheat seedling. Compared with the treatment without P application (-P) at 5 ℃, phosphate fertilizer treatment (+P) promoted the growth of wheat seedling. Shoot and root biomass increased by 18.2% and 33.3%, the accumulation of phosphorus in shoot and root were increased by 30.6% and 13.3%, and the root-shoot ratio, plant height, tillering number and root activity were increased by 3.5%, 10.0%, 10.5% and 70.3%, respectively. At 15 ℃, the effect of phosphorus fertilizer application did not affect wheat biomass and tiller, increased P accumulation in shoot and root of wheat by 32.3% and 23.8%, and increased the ratio of root to shoot, plant height and root activity by 15.6%, 2.5% and 32.8% respectively. There were no significant promoting effects on wheat growth between different phosphate applications at 25 ℃. At three temperatures, phosphate application significantly increased the contents of Olsen-P, Ca2-P, Ca8-P, Al-P and Fe-P. When treated with -P and +P, temperature had no significant effect on Ca2-P content, but had significant effect on the Olsen-P, Ca8-P, Al-P, Fe-P contents. The contents of Ca8-P and Fe-P were 5 ℃＞15 ℃＞25 ℃; Al-P content was 25 ℃＞15 ℃＞5 ℃. Wheat could absorb and utilize Ca2-P, Ca8-P, Al-P, Fe-P at seedling stage. The availability of Al-P, Fe-P to wheat was significantly lower than that of Ca2-P, Ca8-P. There was no significant difference of soil pH, O-P and Ca10-P across all treatments. In conclusion, temperature mainly affected the absorption of phosphorus by affecting wheat growth, and the application of phosphorus fertilizer at low temperature could significantly promote the growth of wheat. High temperature could accelerate the fixation of available phosphorus in calcareous soil, a process could be alleviated by phosphorus application.

Chronic infusion of berberine into the hypothalamic paraventricular nucleus attenuates hypertension and sympathoexcitation via the ROS/Erk1/2/iNOS pathway.

BACKGROUND: Berberine (BBR), a Chinese traditional herbal medicine, has many pharmacologic benefits such as anti-inflammation and anti-oxidation. It is widely used in clinical treatment of cardiovascular diseases such as hypertension. However, the mechanism of how BBR attenuates hypertension through affecting central neural system is not clear. PURPOSE: This study was designed to determine whether chronic infusion of BBR into the hypothalamic paraventricular nucleus (PVN) attenuates hypertension and sympathoexcitation via the ROS/Erk1/2/iNOS pathway. METHODS: Two-kidney, one-clip (2K1C) renovascular hypertensive rats were randomly assigned and treated with bilateral PVN infusion of BBR (2µg/h) or vehicle (artificial cerebrospinal fluid) via osmotic minipumps for 28 days. RESULTS: 2K1C rats showed higher mean arterial pressure (MAP) and PVN Fra-like activity, plasma levels of norepinephrine (NE), PVN levels of NOX2, NOX4, Erk1/2 and iNOS, and lower PVN levels of copper/zinc superoxide dismutase (Cu/Zn-SOD). Chronic infusion of BBR reduced MAP, PVN Fra-like activity and plasma levels of NE, reduced NOX2, NOX4, Erk1/2, iNOS and induced Cu/Zn-SOD in the PVN. CONCLUSIONS: These results suggest that BBR attenuates hypertension and sympathoexcitation via the ROS/Erk1/2/iNOS pathway in 2K1C renovascular hypertensive rats.

Oral CoQ10 attenuates high salt-induced hypertension by restoring neurotransmitters and cytokines in the hypothalamic paraventricular nucleus.

High salt intake leads to an increase in some proinflammatory cytokines and neurotransmitters involved in the pathogenesis of hypertension. The purpose of this work was to know if oral administration of anti-oxidant and free-radical scavenger CoQ10 may attenuate high salt-induced hypertension via regulating neurotransmitters and cytokines in the hypothalamic paraventricular nucleus (PVN). Adult male Sprague-Dawley (SD) rats were fed with a normal salt diet (NS, 0.3% NaCl) or a high salt diet (HS, 8% NaCl) for 15 weeks to induce hypertension. These rats received CoQ10 (10 mg/kg/day) dissolved in olive oil was given by gavage (10 mg/kg/day) for 15 weeks. HS resulted in higher mean arterial pressure (MAP) and the sympathetic nerve activity (RSNA). These HS rats had higher PVN levels of norepinephrine (NE), tyrosine hydroxylase (TH), interleukin (IL)-1ß, NOX2 and NOX4, lower PVN levels of gamma-aminobutyric acid (GABA), IL-10, copper/zinc superoxide dismutase (Cu/Zn-SOD) and the 67-kDa isoform of glutamate decarboxylase (GAD67), as compared with NS group. CoQ10 supplementation reduced NE, TH, IL-1ß, NOX2 and NOX4 in the PVN, and induced IL-10, Cu/Zn-SOD and GAD67 in the PVN. These findings suggest that CoQ10 supplementation restores neurotransmitters and cytokines in the PVN, thereby attenuating high salt-induced hypertension.

[Gastric dynamics analysis of TEAS combined SNP induced general anesthesia when controlled hypotension dropped to 60% of the MAP baseline].

OBJECTIVE: To observe the effect of gastric dynamics by transcutaneous electrical acupoint stimulation (TEAS) combined general anesthesia when controlled hypotension dropped to 60% of the mean arterial prenssure (MAP) baseline, and to provide experimental evidence for organ protection in clinical controlled hypotension. METHODS: Eighteen male beagles were randomly divided into three groups, the general anesthesia group (blank), the general anesthesia induced controlled hypotension group (control), and the general anesthesia combined TEAS induced controlled hypotension group (experiment), 6 in each group. Controlled hypotension was performed in the latter two groups with isoflurane inhalation and intravenous injection of sodium nitroprusside (SNP). The mean arterial pressure (MAP) was lowered to 60% of the MAP baseline and kept for 60 min. Controlled hypotension was not performed in Beagles of the control group. For Beagles in the experiment group, TEAS [2/100 Hz, (4 ± 1) mA] was applied to bilateral Hegu (LI4), Quchi (LI11), Zusanli (ST36), and Sanyinjiao (SP6) from stable physiological conditions to the end of maintaining stages. Changes of EGG frequencies and EGG amplitudes were monitored. Serum levels of gastrin (GAS) and motilin (MTL) were also detected at corresponding time points during and after experiment. RESULTS: As for the pressure control effect of TEAS combined general anesthesia in the controlled hypotension, during the process of controlled hypotension (T1-T4), MAP levels of two controlled pressure groups remained relatively stable, and were kept at 60% of the MAP baseline. When the blood pressure dropped to the target low MAP and maintained at 60 min (T1-T4), EGG amplitudes of Beagles in all the three groups showed decreasing tendency. But it was more obviously lower than its basic level in the control group (P <0.05), while it was not obviously decreased in the experiment group (P < 0.05). EGG frequencies of Beagles in all the three groups showed no obvious change during this stage. By the end of the MAP rising stage (T8), the EGG amplitude of the experimental group was significantly higher than that of the control group and the blank group (P < 0.05), while it didn' t show any obvious increase in the control group. During this period, EGG frequencies of the two controlled hypotension groups decreased more than those of the blank group. Two h after rising blood pressure (at T9), EGG amplitudes and frequencies in the two controlled hypotension groups basically restored to their respective baselines and levels of the blank group at T9. At 2 h (T9) after controlled hypotension, serum levels of GAS and MTL were lower than those of basic levels in the two controlled hypotension groups (P <0.05). However, serum levels of GAS and MTL had an increasing trend in the two controlled hypotension groups at 24-72 h (T10-T12). Besides, the increasing speed and amplitude was better in experiment group than in the control group at T10-T12. However, there was no statistical difference between the two groups (P > 0.05). At 72 h (T12) serum levels of GAS and MTL had basically restored to their basic levels in the two controlled hypotension groups and that of the blank control group. CONCLUSION: EGG amplitudes could be effectively improved in TEAS combined general anesthesia for controlled hypotension at 60% of the MAP baseline, the recovery of the serum GAS level accelerated, gastric power improved and stomach protected.

[Effects of transcutaneous electrical acupoint stimulation combined with general anesthesia for controlled hypotension on heart function and oxidation resistance of myocardium].

OBJECTIVE: To investigate the intervention effect of transcutaneous electrical acupoint sitmulation (TEAS) on heart under limiting level of controlled hypotension. METHODS: Eighteen male Beagles were randomly divided into a general anesthesia group, a control group and an experimental group, 6 dogs in each group. All animals were applied with general anesthesia, and the animals of the control group and the experimental group were administered with combination of isoflurane and sodium nitroprusside (SNP) for controlled hypotension to 30% mean arterial pressure (30% MAP) of base line for 60 min. In the experimental group, TEAS (2 Hz/100 Hz, 6-8 mA) was applied to "Hegu" (LI4), "Zusanli" (ST 36), "Sanyinjiao" (SP 6) and "Quchi" (LI 11) from the beginning of physiological conditions stability to the end of maintained low MAP for 60 min. Creatine kinase isoenzymes MB (CK-MB) and lactate dehydrogenase (LDH) activity were detected at the base line and 2 h, 24 h, 48 h, 72 h after operation. Total superoxide dismutase (T-SOD) and malondialdehyde (MDA) in myocardium were observed at 72 h after operation. RESULTS: The peak of LDH arrived at 24 h after operation and then restored in 3 groups. Compared with basal level, the activity of LDH in controlled group at 72 h after operation was significantly increased (P < 0.05), and in the other two groups no obvious change (P > 0.05). The activity of CK-MB arrived to peak from 2 h to 24 h after operation, and then came back gradually in 3 groups. Compared with postoperative 72 h of the same group, the control group at 48 h significantly increased (P < 0.05), while the other two groups had no statistically significant difference (P > 0.05). The content of MDA at 72 h after operation in controlled group was higher significantly than that in the general anesthesia group and the experimental group (both P < 0.05). CONCLUSION: TEAS combined with anesthesia for controlled hypotension can elevate myocardial effect of anti-oxide free radical, reduce the postoperative release of LDH and CK-MB, so as to produce myocardial protection.

[Effects of transcutaneous electrical acupoint stimulation combined with general anesthesia on changes of gastric dynamics in controlled hypotension dogs].

OBJECTIVE: To observe the effect of transcutaneous electrical acupoint stimulation (TEAS) combined with general anesthesia on gastric dynamics in controlled hypotension dogs, so as to provide experimental evidence for compound acupuncture anesthesia. METHODS: Eighteen male beagle dogs were randomly divided into general anesthesia group (GA group, n = 6), general anesthesia + controlled hypotension group (GA + OHT group, n = 6) and general anesthesia combined with TEAS + controlled hypotension group (TEAS group, n = 6). The latter two groups were administered with the same anesthetics [isofluane inhalation and intravenous sodium nitroprusside (SNP)] for inducing controlled hypotension (being the 40% of the baseline level). Beagles of the GA group were not treated with controlled hypotension (the initial concentration of SNP = 1 microg/kg x min(-1), and with an increase rate of 1 microg/kg x min(-1) until the controlled hypotension phase). In the TEAS group, TEAS [2 Hz/100 Hz, (4 +/- 1) mA]was applied to "Quchi" (LI 11) , "Zusanli" (ST 36), "Hegu" (LI 4), and "Sanyinjiao" (SP 6) from the beginning of the stable physiological condition phase to the end of the controlled-low mean arterial pressure (MAP) phase. Electrogastrogram (EGG) was recorded, and serum gastrin (GAS) and motilin (MTL) contents were detected by enzyme-linked immunosorbent assay. RESULTS: Compared with the basic level, the amplitude value of EGG at 60 mm after controlled hypotension in the GA + CHT group was significantly lower (P < 0.05), while the amplitude level of EGG of the TEAS group at the time-point of MAP recovery was significantly higher than those of the GA and GA + CHT groups (P < 0.05). No significant changes were found among the 3 groups in the frequency levels of EGG. At the time-points of MAP recovery and 2 h after MAP recovery, serum MTL and GAS levels in the TEAS group were close to their basic level (P > 0.05), and serum GAS level at the time-point of 2 h after MAP recovery in the TEAS group was considerably higher than those in the GA and GA + CHT groups (P < 0.05). Twenty-four, 48 and 72 h after MAP recovery, serum GAS levels in the TEAS group were moderately (24 h and 48 h ) and significantly (72 h) higher than that of the basic level. No significant differences were found between the GA and GA + CHT groups in serum MTL and GAS levels at the time-points of 2, 24, 48 and 72 h after MAP recovery (P > 0.05). CONCLUSION: TEAS combining with general anesthesia for controlled hypotension can improve the amplitude of EGG, and serum MTL and GAS contents, favoring the recovery of gastric dynamics and the functional protection of stomach.