UNASSIGNED: Attention deficit hyperactivity disorder (ADHD), a prevalent neurodevelopmental disorder in children, can be effectively alleviated by the herbal preparation Long Mu Qing Xin Mixture (LMQXM), but its mechanism has not been fully elucidated.
UNASSIGNED: To scrutinize the potential pharmacological mechanisms by which LMQXM improves behavior in spontaneously hypertensive rats (SHR/NCrl).
UNASSIGNED: The SHR/NCrl rats were randomly stratified into the model (SHR) group, the methylphenidate hydrochloride (MPH) group, and groups subjected to varying dosages of LMQXM into the medium dose (MD) group with a clinically effective dose, the low dose (LD) group with 0.5 times the clinically effective dose, and high dose (HD) group with 2 times the clinically effective dose. Furthermore, the WKY/NCrl rats constituted the control group. The evaluation of behavior involved the open field test and the Morris water maze test. HPLC, LC-MS, ELISA, immunohistochemistry, Western blot, and RT-qPCR were utilized to scrutinize the catecholamine neurotransmitter content and the expression of proteins and genes associated with the dopamine receptor D1 (DRD1)/cAMP/protein kinase A (PKA)-cAMP response element-binding (CREB) pathway in prefrontal cortex (PFC) and striatum.
UNASSIGNED: MPH and LMQXM ameliorated hyperactivity and learning and memory deficits of SHR/NCrl rats. Among them, LMQXM-MD and MPH also upregulated dopamine (DA), norepinephrine (NE), adenylate cyclase (AC) and cAMP levels, and the expression of proteins and genes associated with the DRD1/cAMP/PKA-CREB pathway in PFC and striatum of SHR/NCrl rats. PFC and striatum DA levels were also upregulated in the LMQXM-LD group as well as the striatum DA levels in the LMQXM-HD group, but there were no statistically significant differences in their NE levels compared to the SHR group. LMQXM-LD and LMQXM-HD also upregulated some DRD1/cAMP/PKA-CREB pathway-related proteins and gene expression, but the effects were discernibly disparate in PFC and striatum. Upon comprehensive analysis, LMQXM-MD appeared to be the most effective dose.
UNASSIGNED: Our study tentatively suggests that LMQXM may rectify hyperactivity and learning and memory deficits of SHR/NCrl rats by elevating catecholamine neurotransmitters in the PFC and striatum. This effect may be attributed to the potential activation of the DRD1/cAMP/PKA-CREB signaling pathway, which appears to achieve an optimal response at moderate doses.

UNASSIGNED: Investigating the effects of electroacupuncture (EA) treatment on cardiovascular function and aortic lipid profiles in spontaneously hypertensive rats (SHR) constitutes the foundational focus of this study. The overarching goal is to comprehensively elucidate the alterations brought about by EA treatment and to assess its potential as an alternative therapy for hypertension.
UNASSIGNED: Consecutive EA treatments were administered to SHR, and the effects on systolic blood pressure, cardiac function, and hypertension-related neuronal signals were assessed. Aortic lipid profiles in vehicle-treated SHR and EA-treated SHR groups were analyzed using mass spectrometry-based lipid profiling. Additionally, the expression of Cers2 and GNPAT, enzymes involved in the synthesis of specific aortic lipids, was examined.
UNASSIGNED: The study demonstrated that consecutive EA treatments restored systolic blood pressure, improved cardiovascular function, and normalized hypertension-related neuronal signals in SHR. Analysis of the aortic lipid profiles revealed distinct differences between the vehicle-treated SHR group and the EA-treated SHR group. Specifically, EA treatment significantly altered the levels of aortic sphingomyelin and phospholipids, including very long-chain fatty acyl-ceramides and ether phosphatidylcholines. These changes in aortic lipid profiles correlated significantly with systolic blood pressure and cardiac function indicators. Furthermore, EA treatment significantly altered the expression of Cers2 and GNPAT.
UNASSIGNED: The findings suggest that EA may influence cardiovascular functions and aortic lipid profiles in SHR.

UNASSIGNED: Abnormal hippocampal neurodevelopment, particularly in the dentate gyrus region, may be a key mechanism of attention-deficit/hyperactivity disorder (ADHD). In this study, we investigate the effect of the most commonly used Chinese herb for the treatment of ADHD, Rehmanniae Radix Preparata (RRP), on behavior and hippocampal neurodevelopment in spontaneously hypertensive rats (SHR).
UNASSIGNED: Behavior tests, including Morris water maze (MWM) test, open field test (OFT) and elevated plus maze (EPM) test were performed to assess the effect of RRP on hyperactive and impulsive behavior. Hippocampal neurodevelopment was characterized by transmission electron microscopy, immunofluorescence, Golgi staining and Nissl staining approaches. Regulatory proteins such as Trkb, CDK5, FGF2/FGFR1 were examined by Western blot analysis.
UNASSIGNED: The results showed that RRP could effectively control the impulsive and spontaneous behavior and improve the spatial learning and memory ability. RRP significantly reduced neuronal loss and increased the number of hippocampal stem cells, and promoted synaptic plasticity. In addition, FGF/FGFR signaling was upregulated after RRP treatment.
UNASSIGNED: RRP can effectively reduce impulsive and spontaneous behavior and ameliorate hippocampal neurodevelopmental abnormalities in ADHD rat model.

The central exacerbating factor in the pathophysiology of ischemic-reperfusion acute kidney injury (AKI) is oxidative stress. Lipid peroxidation and DNA damage in ischemia are accompanied by the formation of 3-nitrotyrosine, a biomarker for oxidative damage. DNA double-strand breaks (DSBs) may also be a result of postischemic AKI. γH2AX(S139) histone has been identified as a potentially useful biomarker of DNA DSBs. On the other hand, hypoxia-inducible factor (HIF) is the \"master switch\" for hypoxic adaptation in cells and tissues. The aim of this research was to evaluate the influence of hyperbaric oxygen (HBO) preconditioning on antioxidant capacity estimated by FRAP (ferric reducing antioxidant power) and ABTS (2,2\'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)) assay, as well as on oxidative stress parameter 3-nitrotyrosine, and to assess its effects on γH2AX(S139), HIF-1α, and nuclear factor-κB (NF-κB) expression, in an experimental model of postischemic AKI induced in spontaneously hypertensive rats. The animals were divided randomly into three experimental groups: sham-operated rats (SHAM, n = 6), rats with induced postischemic AKI (AKI, n = 6), and group exposed to HBO preconditioning before AKI induction (AKI + HBO, n = 6). A significant improvement in the estimated glomerular filtration rate, eGFR, in AKI + HBO group (p < 0.05 vs. AKI group) was accompanied with a significant increase in plasma antioxidant capacity estimated by FRAP (p < 0.05 vs. SHAM group) and a reduced immunohistochemical expression of 3-nitrotyrosine and γH2AX(S139). Also, HBO pretreatment significantly increased HIF-1α expression (p < 0.001 vs. AKI group), estimated by Western blot and immunohistochemical analysis in kidney tissue, and decreased immunohistochemical NF-κB renal expression (p < 0.01). Taking all of these results together, we may conclude that HBO preconditioning has beneficial effects on acute kidney injury induced in spontaneously hypertensive rats.

Changes in lighting accompany modern urbanization trends and can lead to various pathologies based on circadian disturbances. In this study, we assessed the changes in the circadian rhythm of core body temperature (Tcore) and locomotor activity of Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) following exposure to different lighting conditions: extended light phase of the day (16 h-8 h, 20 h-4 h, 24 h-0 h), light pollution, monochromatic light, and bright light therapy. The telemetry data was collected after experimental lighting conditions during periods with standard lighting (12 h of light and 12 h of darkness) and was processed using linear and cosinor analysis. The daily rhythms of rats\' parameters persisted in accordance with the standard lighting regime. Tcore changes were observed in both groups compared to the initial period: in WKY, a decrease in Tcore during the darkness and an increase during the light; in SHR, the opposite trend, with Tcore increased during the darkness and decreased during the light phase of the day. A relationship between Tcore and activity was observed with weak correlation. WKY exhibited more pronounced signs of adaptive variation and desynchronization compared to SHR, which could be associated with a wider range of functional capabilities of the organism without cardiovascular pathology.

3-demethyl-2-geranyl-4-prenylbellidifoline (DGP), a natural xanthone isolated from Garcinia achachairu, has previously demonstrated remarkable diuretic and renal protective actions. The present study expands its actions on the cardiovascular system by evaluating its vasorelaxant and blood pressure-lowering effects in spontaneously hypertensive rats (SHRs). Aortic endothelium-intact (E+) preparations of SHRs pre-contracted by phenylephrine and exposed to cumulative concentrations of G. achachairu extract, fractions, and DGP exhibited a significant relaxation compared to vehicle-only exposed rings. The non-selective muscarinic receptor antagonist (atropine), the non-selective inhibitor of nitric oxide synthase (L-NAME), as well as the inhibitor of soluble guanylate cyclase (ODQ) altogether avoided DGP-induced relaxation. Tetraethylammonium (small conductance Ca2+-activated K+ channel blocker), 4-aminopyridine (a voltage-dependent K+ channel blocker), and barium chloride (an influx-rectifying K+ channel blocker) significantly reduced DGP capacity to induce relaxation without the interference of glibenclamide (an ATP-sensitive inward rectifier 6.1 and 6.2 K+ channel blocker). Additionally, administration of DGP, 1 mg/kg i.v., decreased the mean, systolic, and diastolic arterial pressures, and the heart rate of SHRs. The natural xanthone DGP showed promising potential as an endothelium-dependent vasorelaxant, operating through the nitric oxide pathway and potassium channels, ultimately significantly reducing blood pressure in hypertensive rats.

Natural compounds, known for diverse pharmacological properties, have attracted attention as potential sources for hypertension treatment. Previous studies have revealed the hypotensive effect and vascular relaxation of prunetin, a natural compound derived from Prunus yedoensis. However, the potential blood pressure-lowering and vasorelaxant effects of sakuranetin, another representative compound found in plants belonging to the genus Prunus, have remained unexplored. We aimed to fill this gap by investigating the hypotensive and vasorelaxant effects of sakuranetin in rats. Results indicated that sakuranetin, particularly in the sakuranetin 20 mg/kg group, led to significant reductions in systolic blood pressure (SBP) and diastolic blood pressure (DBP) by -14.53 ± 5.64% and -19.83 ± 6.56% at 4 h after administration. In the sakuranetin 50 mg/kg group, the SBP and DBP decreased by -13.27 ± 6.86% and -16.62 ± 10.01% at 2 h and by -21.61 ± 4.49% and -30.45 ± 5.21% at 4 h after administration. In addition, we identified the vasorelaxant effects of sakuranetin, attributing its mechanisms to the inhibition of calcium influx and the modulation of angiotensin II. Considering its hypotensive and vasorelaxant effects, sakuranetin could potentially serve as an antihypertensive agent. However, further research is required to evaluate the safety and long-term efficacy.

We studied whether the function of presynaptic inhibitory cannabinoid CB1 receptors on the sympathetic nerve fibres innervating resistance vessels is increased in spontaneously hypertensive rats (SHR) like in deoxycorticosterone (DOCA)-salt hypertension. An increase in diastolic blood pressure (DBP) was induced by electrical stimulation of the preganglionic sympathetic neurons or by phenylephrine injection in pithed SHR and normotensive Wistar-Kyoto rats (WKY). The electrically (but not the phenylephrine) induced increase in DBP was inhibited by the cannabinoid receptor agonist CP55940, similarly in both groups, and by the endocannabinoid reuptake inhibitor AM404 in SHR only. The effect of CP55940 was abolished/reduced by the CB1 receptor antagonist AM251 (in both groups) and in WKY by endocannabinoid degradation blockade, i.e., the monoacylglycerol lipase (MAGL) inhibitor MJN110 and the dual fatty acid amide hydrolase (FAAH)/MAGL inhibitor JZL195 but not the FAAH inhibitor URB597. MJN110 and JZL195 tended to enhance the effect of CP55940 in SHR. In conclusion, the function of presynaptic inhibitory CB1 receptors depends on the hypertension model. Although no differences occurred between SHR and WKY under basal experimental conditions, the CB1 receptor function was better preserved in SHR when the endocannabinoid tone was increased by the inhibition of MAGL or the endocannabinoid transporter.

The aim of this study is to investigate whether milk fermented by Lactiplantibacillus plantarum K79, which exhibits angiotensin-converting enzyme inhibitory activity, has an effect on lowering the blood pressure of hypertensive rats and to investigate biomarker changes in their blood. Experimental group: normal group (NG, Wistar-Kyoto rats): distilled water, control group [NCG, spontaneously hypertensive rats (SHR)]: distilled water, high treatment group (HTG, SHR): 500 mg/kg/day, medium treatment group (SHR): 335 mg/kg/day, low treatment group (SHR): 170 mg/kg/day, positive control group (PCG, SHR): Enalapril, 10 mg/kg/day. The experimental animals used in this study were divided into groups composed of 8 animals. In terms of weight change, a significant difference was observed between the NG and the SHR group, but there was no significant difference between the SHR group. After 8 wk of feeding, blood pressure was lowered more significantly in the HTG (209.9±13.3 mmHg) than in the NCG (230.8±7.3 mmHg). The treatment group has an effect of lowering blood pressure by significantly suppressing blood pressure-related biomarker protein expression than NG. The results obtained can be used as an antihypertensive material in a variety of food raw materials.

Hypertension and estrogen deficiency can affect bone metabolism and therefore increase the risk of osseointegration. Antihypertensive drugs such as losartan not only control blood pressure but also enhance bone healing. In addition, alendronate sodium is widely used to treat postmenopausal osteoporosis. Hence, we evaluated the effect of systemic antihypertensive and local alendronate coted on implants on osseointegration under hypertensive and estrogen-deficiency conditions. A total of 64 spontaneously hypertensive rats (SHRs) treated with losartan were randomly divided according to the estrogen-deficiency induction by ovariectomy (OVX) or not (SHAM), and whether the implant surface was coated with sodium alendronate (ALE) or not, resulting in four groups: SHR SHAM, SHR SHAM ALE, SHR OVX, and SHR OVX ALE. The removal torque, microcomputed tomography, and epifluorescence microscopy were the adopted analyses. The hypertensive and estrogen-deficiency animals presented a lower removal torque even when treated with alendronate on implant surface. The microcomputed tomography revealed a higher bone volume and bone-to-implant contact in the SHRs than the SHR OVX rats. Epifluorescence showed a decreased mineral apposition ratio in the SHR OVX ALE group. The data presented indicate that estrogen deficiency impairs osseointegration in hypertensive rats; in addition, alendronate coated on the implant surface does not fully reverse this impaired condition caused by estrogen deficiency.