High salt intake increases blood pressure, and dietary salt intake has been clearly demonstrated to be associated with hypertension incidence. Japanese people consume higher amounts of salt than Westerners. It has been reported that miso soup was one of the major sources of daily salt intake in Japanese people. Adding salt is indispensable to make miso, and therefore, in some cases, refraining from miso soup is recommended to reduce dietary salt intake. However, recent studies using salt-sensitive hypertensive models have revealed that miso lessens the effects of salt on blood pressure. In other word, the intake of miso dose not increase the blood pressure compared to the equivalent intake of salt. In addition, many clinical observational studies have demonstrated the absence of a relationship between the frequency of miso soup intake and blood pressure levels or hypertension incidence. The mechanism of this phenomenon seen in the subjects with miso soup intake has not been fully elucidated yet. However, in basic studies, it was found that the ingredients of miso attenuate sympathetic nerve activity, resulting in lowered blood pressure and heart rate. Therefore, this review focused on the differences between the effects of miso intake and those of the equivalent salt intake on sympathetic nerve activity, blood pressure, and heart rate.
Blood Pressure ; drug effects ; physiology ; Heart Rate ; drug effects ; physiology ; Humans ; Soy Foods ; adverse effects ; Sympathetic Nervous System ; drug effects ; physiology

Chronic intermittent hypobaric hypoxia (CIHH) is known to have an anti-hypertensive effect, which might be related to modulation of the baroreflex in rats with renal vascular hypertension (RVH). In this study, RVH was induced by the 2-kidney-1-clip method (2K1C) in adult male Sprague-Dawley rats. The rats were then treated with hypobaric hypoxia simulating 5000 m altitude for 6 h/day for 28 days. The arterial blood pressure (ABP), heart rate (HR), and renal sympathetic nerve activity (RSNA) were measured before and after microinjection of L-arginine into the nucleus tractus solitarii (NTS) in anesthetized rats. Evoked excitatory postsynaptic currents (eEPSCs) and spontaneous EPSCs (sEPSCs) were recorded in anterogradely-labeled NTS neurons receiving baroreceptor afferents. We measured the protein expression of neuronal nitric oxide synthase (nNOS) and endothelial NOS (eNOS) in the NTS. The results showed that the ABP in RVH rats was significantly lower after CIHH treatment. The inhibition of ABP, HR, and RSNA induced by L-arginine was less in RVH rats than in sham rats, and greater in the CIHH-treated RVH rats than the untreated RVH rats. The eEPSC amplitude in NTS neurons receiving baroreceptor afferents was lower in the RVH rats than in the sham rats and recovered after CIHH. The protein expression of nNOS and eNOS in the NTS was lower in the RVH rats than in the sham rats and this decrease was reversed by CIHH. In short, CIHH treatment decreases ABP in RVH rats via up-regulating NOS expression in the NTS.
Animals ; Baroreflex ; physiology ; Blood Pressure ; drug effects ; Hypertension ; metabolism ; Hypoxia ; chemically induced ; Kidney ; drug effects ; metabolism ; Male ; Nitric Oxide Synthase Type I ; drug effects ; metabolism ; Rats, Sprague-Dawley ; Solitary Nucleus ; metabolism

Intermedin/adrenomedullin-2 (IMD/AM2), a member of the calcitonin gene-related peptide/AM family, plays an important role in protecting the cardiovascular system. However, its role in the enhanced sympathoexcitation in obesity-related hypertension is unknown. In this study, we investigated the effects of IMD in the paraventricular nucleus (PVN) of the hypothalamus on sympathetic nerve activity (SNA), and lipopolysaccharide (LPS)-induced sympathetic activation in obesity-related hypertensive (OH) rats induced by a high-fat diet for 12 weeks. Acute experiments were performed under anesthesia. The dynamic alterations of sympathetic outflow were evaluated as changes in renal SNA and mean arterial pressure (MAP) in response to specific drugs. Male rats were fed a control diet (12% kcal as fat) or a high-fat diet (42% kcal as fat) for 12 weeks to induce OH. The results showed that IMD protein in the PVN was downregulated, but Toll-like receptor 4 (TLR4) and plasma norepinephrine (NE, indicating sympathetic hyperactivity) levels, and systolic blood pressure were increased in OH rats. LPS (0.5 µg/50 nL)-induced enhancement of renal SNA and MAP was greater in OH rats than in obese or control rats. Bilateral PVN microinjection of IMD (50 pmol) caused greater decreases in renal SNA and MAP in OH rats than in control rats, and inhibited LPS-induced sympathetic activation, and these were effectively prevented in OH rats by pretreatment with the AM receptor antagonist AM22-52. The mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) inhibitor U0126 in the PVN partially reversed the LPS-induced enhancement of SNA. However, IMD in the PVN decreased the LPS-induced ERK activation, which was also effectively prevented by AM22-52. Chronic IMD administration resulted in significant reductions in the plasma NE level and blood pressure in OH rats. Moreover, IMD lowered the TLR4 protein expression and ERK activation in the PVN, and decreased the LPS-induced sympathetic overactivity. These results indicate that IMD in the PVN attenuates SNA and hypertension, and decreases the ERK activation implicated in the LPS-induced enhancement of SNA in OH rats, and this is mediated by AM receptors.
Adrenomedullin ; metabolism ; Animals ; Blood Pressure ; drug effects ; physiology ; Hypertension ; etiology ; Lipopolysaccharides ; pharmacology ; Male ; Neuropeptides ; metabolism ; Obesity ; complications ; Rats, Sprague-Dawley ; Receptors, Adrenomedullin ; drug effects ; metabolism ; Sympathetic Nervous System ; drug effects ; metabolism ; Toll-Like Receptor 4 ; metabolism

OBJECTIVE: To observe the immediate effect and safety of Shexiang Tongxin dropping pills (, STDP) on patients with coronary slow flow (CSF), and furthermore, to explore new evidence for the use of Chinese medicine in treating ischemic chest pain. METHODS: Coronary angiography (CAG) with corrected thrombolysis in myocardial infarction (TIMI) frame count (CTFC) was applied (collected at 30 frames/s). The treatment group included 22 CSF patients, while the control group included 22 individuals with normal coronary flow. CSF patients were given 4 STDP through sublingual administration, and CAG was performed 5 min after the medication. The immediate blood flow frame count, blood pressure, and heart rate of patients before and after the use of STDP were compared. The liver and kidney functions of patients were examined before and after treatments. RESULTS: There was a significant difference in CTFC between groups (P<0.05). The average CTFC values of the vessels with slow blood flow in CSF patients were, respectively, 49.98 ± 10.01 and 40.42 ± 11.33 before and after the treatment with STDP, a 19.13% improvement. The CTFC values (frame/s) measured before and after treatment at the left anterior descending coronary artery, left circumflex artery, and right coronary artery were, respectively, 48.00 ± 13.32 and 41.80 ± 15.38, 59.00 ± 4.69 and 50.00 ± 9.04, and 51.90 ± 8.40 and 40.09 ± 10.46, giving 12.92%, 15.25%, and 22.76% improvements, respectively. The CTFC values of vessels with slow flow before treatment were significantly decreased after treatment (P<0.05). There were no apparent changes in the heart rate, blood pressure, or liver or kidney function of CSF patients after treatment with STDP (all P>0.05). CONCLUSIONS The immediate effect of STDP in treating CSF patients was apparent. This medication could significantly improve coronary flow without affecting blood pressure or heart rate. Our findings support the potential of Chinese medicine to treat ischemic chest pain.
Blood Pressure ; drug effects ; Coronary Circulation ; drug effects ; physiology ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Female ; Heart Rate ; drug effects ; Humans ; Kidney ; drug effects ; physiopathology ; Liver ; drug effects ; physiopathology ; Male ; Middle Aged ; No-Reflow Phenomenon ; drug therapy ; physiopathology

Panax notoginseng saponins (PNS) are the major components of Panax notoginseng, with multiple pharmacological activities but poor oral bioavailability. PNS could be metabolized by gut microbiota in vitro, while the exact role of gut microbiota of PNS metabolism in vivo remains poorly understood. In this study, pseudo germ-free rat models were constructed by using broad-spectrum antibiotics to validate the gut microbiota-mediated transformation of PNS in vivo. Moreover, a high performance liquid chromatography-electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS) was developed for quantitative analysis of four metabolites of PNS, including ginsenoside F1 (GF1), ginsenoside Rh2 (GRh2), ginsenoside compound K (GCK) and protopanaxatriol (PPT). The results showed that the four metabolites could be detected in the control rat plasma, while they could not be determined in pseudo germ-free rat plasma. The results implied that PNS could not be biotransformed effectively when gut microbiota was disrupted. In conclusion, gut microbiota plays an important role in biotransformation of PNS into metabolites in vivo.
Animals ; Anti-Bacterial Agents ; pharmacology ; Biotransformation ; Chromatography, High Pressure Liquid ; Feces ; microbiology ; Gastrointestinal Microbiome ; drug effects ; physiology ; Ginsenosides ; blood ; Male ; Panax notoginseng ; chemistry ; Rats, Sprague-Dawley ; Sapogenins ; blood ; Saponins ; administration & dosage ; metabolism ; Tandem Mass Spectrometry

OBJECTIVETo investigate whether the methanol extract of Berberis amurensis Rupr. (BAR) augments penile erection using in vitro and in vivo experiments.

METHODSThe ex vivo study used corpus cavernosum strips prepared from adult male New Zealand White rabbits. In in vivo studies for intracavernous pressure (ICP), blood pressure, mean arterial pressure (MAP), and increase of peak ICP were continuously monitored during electrical stimulation of Sprague-Dawley rats.

RESULTSPreconstricted with phenylephrine (PE) in isolated endotheliumintact rabbit corus cavernosum, BAR relaxed penile smooth muscle in a dose-dependent manner, which was inhibited by pretreatment with NG-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor, and H-[1,2,4]-oxadiazole-[4,3-α]-quinoxalin-1-one, a soluble guanylyl cclase inhibitor. BAR significantly relaxed penile smooth muscles dose-dependently in ex vivo, and this was inhibited by pretreatment with L-NAME H-[1,2,4]-oxadiazole-[4,3-α]-quinoxalin-1-one. BAR-induced relaxation was significantly attenuated by pretreatment with tetraethylammonium (TEA, P<0.01), a nonselective K channel blocker, 4-aminopyridine (4-AP, P<0.01), a voltage-dependent K channel blocker, and charybdotoxin (P<0.01), a large and intermediate conductance Ca sensitive-K channel blocker, respectively. BAR induced an increase in peak ICP, ICP/MAP ratio and area under the curve dose dependently.

CONCLUSIONBAR augments penile erection via the nitric oxide/cyclic guanosine monophosphate system and Ca sensitive-K (BK and IK) channels in the corpus cavernosum.

Animals ; Area Under Curve ; Berberis ; chemistry ; Blood Pressure ; drug effects ; Cyclic GMP ; metabolism ; Epoprostenol ; pharmacology ; In Vitro Techniques ; Indomethacin ; pharmacology ; Male ; Models, Biological ; Muscle Relaxation ; drug effects ; Muscle, Smooth ; drug effects ; physiology ; NG-Nitroarginine Methyl Ester ; pharmacology ; Nitric Oxide ; metabolism ; Penile Erection ; drug effects ; Phenylephrine ; pharmacology ; Plant Extracts ; pharmacology ; Potassium Channel Blockers ; pharmacology ; Potassium Channels ; metabolism ; Pressure ; Rabbits

BACKGROUNDPropofol is increasingly used during partial support mechanical ventilation such as pressure support ventilation (PSV) in postoperative patients. However, breathing pattern, respiratory drive, and patient-ventilator synchrony are affected by the sedative used and the sedation depth. The present study aimed to evaluate the physiologic effects of varying depths of propofol sedation on respiratory drive and patient-ventilator synchrony during PSV in postoperative patients.

METHODSEight postoperative patients receiving PSV for <24 h were enrolled. Propofol was administered to achieve and maintain a Ramsay score of 4, and the inspiratory pressure support was titrated to obtain a tidal volume (VT) of 6-8 ml/kg. Then, the propofol dose was reduced to achieve and maintain a Ramsay score of 3 and then 2. At each Ramsay level, the patient underwent 30-min trials of PSV. We measured the electrical activity of the diaphragm, flow, airway pressure, neuro-ventilatory efficiency (NVE), and patient-ventilator synchrony.

RESULTSIncreasing the depth of sedation reduced the peak and mean electrical activity of the diaphragm, which suggested a decrease in respiratory drive, while VT remained unchanged. The NVE increased with an increase in the depth of sedation. Minute ventilation and inspiratory duty cycle decreased with an increase in the depth of sedation, but this only achieved statistical significance between Ramsay 2 and both Ramsay 4 and 3 (P < 0.05). The ineffective triggering index increased with increasing sedation depth (9.5 ± 4.0%, 6.7 ± 2.0%, and 4.2 ± 2.1% for Ramsay 4, 3, and 2, respectively) and achieved statistical significance between each pair of depth of sedation (P < 0.05). The depth of sedation did not affect gas exchange.

CONCLUSIONSPropofol inhibits respiratory drive and deteriorates patient-ventilator synchrony to the extent that varies with the depth of sedation. Propofol has less effect on breathing pattern and has no effect on VT and gas exchange in postoperative patients with PSV.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Blood Pressure ; drug effects ; physiology ; Female ; Hemodynamics ; drug effects ; physiology ; Humans ; Intensive Care Units ; Male ; Middle Aged ; Positive-Pressure Respiration ; methods ; Propofol ; therapeutic use ; Prospective Studies ; Respiration, Artificial ; methods ; Tidal Volume ; drug effects ; physiology ; Young Adult

PURPOSE: Urapidil is putatively effective for patients with hypertension and acute heart failure, although randomized controlled trials thereon are lacking. We investigated the efficacy and safety of intravenous urapidil relative to that of nitroglycerin in older patients with hypertension and heart failure in a randomized controlled trial. MATERIALS AND METHODS: Patients (>60 y) with hypertension and heart failure were randomly assigned to receive intravenous urapidil (n=89) or nitroglycerin (n=91) for 7 days. Hemodynamic parameters, cardiac function, and safety outcomes were compared. RESULTS: Patients in the urapidil group had significantly lower mean systolic blood pressure (110.1±6.5 mm Hg) than those given nitroglycerin (126.4±8.1 mm Hg, p=0.022), without changes in heart rate. Urapidil was associated with improved cardiac function as reflected by lower N terminal-pro B type natriuretic peptide after 7 days (3311.4±546.1 ng/mL vs. 4879.1±325.7 ng/mL, p=0.027) and improved left ventricular ejection fraction (62.2±3.4% vs. 51.0±2.4%, p=0.032). Patients given urapidil had fewer associated adverse events, specifically headache (p=0.025) and tachycardia (p=0.004). The one-month rehospitalization and all-cause mortality rates were similar. CONCLUSION: Intravenous administration of urapidil, compared with nitroglycerin, was associated with better control of blood pressure and preserved cardiac function, as well as fewer adverse events, for elderly patients with hypertension and acute heart failure.
Acute Disease ; Aged ; Antihypertensive Agents/*administration & dosage ; Blood Pressure/drug effects ; Cause of Death ; Female ; Heart Failure/*drug therapy/physiopathology ; Heart Rate/drug effects/physiology ; Hemodynamics ; Humans ; Hypertension/*drug therapy/physiopathology ; Injections, Intravenous ; Male ; Middle Aged ; Natriuretic Peptide, Brain/blood ; Nitroglycerin/administration & dosage ; Peptide Fragments/blood ; Piperazines/*administration & dosage ; Ventricular Function, Left/drug effects/physiology

The purpose of the present study is to investigate the effect of isoliquiritigenin (ISL) on the cerebral basilar artery in spontaneously hypertensive rats (SHR). The change of SHR systolic pressure was measured by tail artery pressure measurement instrument before and after ISL intervention. After perfusion with 1 × 10(-5) mol/L phenylephrine (PE), 1 × 10(-5) mol/L PE + 1 × 10(-4) mol/L ISL and 1 × 10(-5) mol/L PE, the diameter of the cerebral basilar artery separated from SHR was measured by pressure myograph. The current of large-conductance calcium-activated potassium (BKCa) channel of SHR single vascular smooth muscle cell (VSMC) was recorded by whole-cell patch-clamp technique and the cGMP levels of basilar artery was evaluated by ELISA. The results showed that 1) after intervention with ISL for 14 days, the systolic pressure of SHR was decreased from (218.3 ± 1.6) mmHg to (119.2 ± 1.9) mmHg (P < 0.01), but there was no difference in systolic pressure between ISL-treated SHR and Wistar-Kyoto (WKY) rat; 2) 1 × 10(-4) mol/L ISL relaxed the SHR cerebral basilar artery (P < 0.01); 3) ISL significantly increased the outward current density of VSMC from SHR cerebral basilar artery (P < 0.01, n = 6), and the effect could be reversed by 1 × 10(-3) mol/L TEA (a BKCa channel inhibitor), but 3 × 10(-4) mol/L 4-AP (a Kv channel inhibitor) had no effect on the enhanced current density induced by ISL in VSMC; 4) 1 × 10(-5) mol/L Methylene blue (a sGC inhibitor) significantly inhibited the ISL-enhanced current density in VSMC (P < 0.05, n = 6); 5) ISL significantly increased the cGMP level of SHR basilar artery (P < 0.05, n = 6). The results suggest that the role of the ISL in relaxing the SHR cerebral basilar artery may be related to its effect in enhancing BKCa current by increasing the levels of cGMP in the VSMC.
Animals ; Basilar Artery ; drug effects ; Blood Pressure ; Cerebral Arteries ; drug effects ; Chalcones ; pharmacology ; Cyclic GMP ; physiology ; Muscle, Smooth, Vascular ; cytology ; Myocytes, Smooth Muscle ; physiology ; Patch-Clamp Techniques ; Potassium Channels, Calcium-Activated ; physiology ; Rats ; Rats, Inbred SHR ; Rats, Inbred WKY ; Systole

BACKGROUNDAs a novel device-based approach targeting the renal sympathetic nerves, percutaneous renal denervation (RDN) has been shown to be effective and safe for reducing blood pressure. However, while considerable data on RDN have been obtained from Western populations, there is limited findings from East Asian populations. The purpose of this study was to evaluate one-year outcomes of RDN for the treatment of resistant hypertension in Chinese patients.

METHODSBetween February and August 2012, 14 patients (mean age 39 ± 8 years, 10 males) with resistant hypertension underwent successful RDN at the Fuwai Hospital. All 14 patients were followed up at 1, 3, 6 and 12 months post-procedure. Blood pressure, use of antihypertensive agents, renal function, and complications were investigated.

RESULTSBaseline values included mean office blood pressure of 164/103 ± 14/10 mmHg, mean 3.9 ± 0.6 anti-hypertensive agents, and an estimated glomerular filtration rate of (79 ± 19) ml × min(-1)×1.73 m(-2). Office blood pressure after the procedure was reduced by -14/-10, -17/-11, -21/-12, and -24/-14 mmHg at 1, 3, 6, and 12 months respectively, and the reduction of the number of antihypertensive agents at the above corresponding time points was -1.3, -1.5, -1.7 and -1.8 respectively (all P < 0.001). The mean reduction of 24-hour ambulatory blood pressure was similar to the reduction of office blood pressure at the four corresponding time points. Renal function did not significantly change at any time point (all P > 0.05). No clinical complications were observed at 12-month follow-up.

CONCLUSIONThis study showed that RDN seems to be effective in reducing blood pressure of Chinese patients with resistant hypertension, with minimal adverse events at 12-month follow-up.

Adult ; Antihypertensive Agents ; therapeutic use ; Blood Pressure ; drug effects ; Female ; Glomerular Filtration Rate ; physiology ; Humans ; Hypertension ; drug therapy ; Male ; Middle Aged