The nucleus tractus solitarius (NTS) is the primary brain region for receiving and integrating cardiovascular afferent signals. It plays a crucial role in maintaining balance of autonomic nervous system and regulating blood pressure through cardiovascular reflexes. Neurons within the NTS form complex synaptic connections and interact reciprocally with other brain regions. The NTS regulates autonomic nervous system activity and arterial blood pressure through modulating baroreflex, sympathetic nerve activity, renin-angiotensin-aldosterone system, and oxidative stress. Dysfunctions in NTS activity may contribute to hypertension. Understanding the NTS' role in centrally regulating blood pressure and alterations of neurotransmission or signaling pathways in the NTS may provide rationale for new therapeutic strategies of prevention and treatment. This review summarizes the research findings on autonomic nervous system regulation and arterial blood pressure control by NTS, as well as unresolved questions, in order to provide reference for future investigation.
Solitary Nucleus/physiopathology* ; Hypertension/physiopathology* ; Humans ; Animals ; Autonomic Nervous System/physiopathology* ; Blood Pressure/physiology* ; Baroreflex/physiology* ; Renin-Angiotensin System/physiology* ; Sympathetic Nervous System/physiology*

The renin-angiotensin-aldosterone system (RAAS) is crucial for regulating blood pressure and maintaining fluid balance, while clock genes are essential for sustaining biological rhythms and regulating metabolism. There exists a complex interplay between RAAS and clock genes that may significantly contribute to the development of various cardiovascular and metabolic diseases. Although current literature has identified correlations between these two systems, the specific mechanisms of their interaction remain unclear. Moreover, the interaction patterns under different physiological and pathological conditions need further investigation. This review summarizes the synergistic roles of the RAAS and clock genes in cardiovascular diseases, explores their molecular mechanisms and pathophysiological connections, discusses the application of chronotherapy, and highlights potential future research directions, aiming to provide novel insights for the prevention and treatment of related diseases.
Humans ; Renin-Angiotensin System/genetics* ; Cardiovascular Diseases/genetics* ; CLOCK Proteins/physiology* ; Animals

The renin angiotensin system (RAS) appears to influence male fertility at multiple levels. In this work, we analyzed the relationship between the RAS and DNA integrity. Fifty male volunteers were divided into two groups (25 each): control (DNA fragmentation ≤20%) and pathological (DNA fragmentation >20%) cases. Activities of five peptidases controlling RAS were measured fluorometrically: prolyl endopeptidase (which converts angiotensin [A] I and A II to A 1-7), neutral endopeptidase (NEP/CD10: A I to A 1-7), aminopeptidase N (APN/CD13: A III to A IV), aminopeptidase A (A II to A III) and aminopeptidase B (A III to A IV). Angiotensin-converting enzyme (A I to A II), APN/CD13 and NEP/CD10 were also assessed by semiquantitative cytometry and quantitative flow cytometry assays, as were the receptors of all RAS components: A II receptor type 1 (AT1R), A II receptor type 2 (AT2R), A IV receptor (AT4R or insulin-regulated aminopeptidase [IRAP]), (pro)renin receptor (PRR) and A 1-7 receptor or Mas receptor (MasR) None of the enzymes that regulate levels of RAS components, except for APN/CD13 (decrease in fragmented cells), showed significant differences between both groups. Micrographs of RAS receptors revealed no significant differences in immunolabeling patterns between normozoospermic and fragmented cells. Labeling of AT1R (94.3% normozoospermic vs 84.1% fragmented), AT4R (96.2% vs 95.3%) and MasR (97.4% vs 87.2%) was similar between the groups. AT2R (87.4% normozoospermic vs 63.1% fragmented) and PRR (96.4% vs 48.2%) were higher in non-fragmented spermatozoa. These findings suggest that fragmented DNA spermatozoa have a lower capacity to respond to bioactive RAS peptides.
Angiotensins ; DNA Fragmentation ; Humans ; Insulin ; Male ; Renin-Angiotensin System/physiology* ; Spermatozoa

Renin-angiotensin system (RAS) is involved in the regulation of vascular smooth muscle cell (VSMC) tension. Angiotensin II (Ang II) as the main effector molecule of RAS can increase the intracellular Ca concentration and cause VSMCs contraction by activating angiotensin II type 1 receptor (AT1R). The large-conductance Ca- and voltage-activated potassium (BK) channel is an essential potassium channel in VSMCs, playing an important role in maintaining membrane potential and intracellular potassium-calcium balance. The BK channel in VSMCs mainly consists of α and β1 subunits. Functional BKα subunits contain voltage-sensors and Ca binding sites. Hence, increase in the membrane potential or intracellular Ca concentration can trigger the opening of the BK channel by mediating transient K outward current in a negative regulatory manner. However, increasing evidence has shown that although Ang II can raise the intracellular Ca concentration, it also inhibits the expression and function of the BK channel by activating the PKC pathway, internalizing AT1R-BKα heterodimer, or dissociating α and β1 subunits. Under some specific conditions, Ang II can also activate the BK channel, but the underlying mechanism remains unknown. In this review, we summarize the potential mechanisms underlying the inhibitory or activating effect of Ang II on the BK channel, hoping that it could provide a theoretical basis for improving intracellular ion imbalance.
Angiotensin II ; physiology ; Calcium ; physiology ; Humans ; Large-Conductance Calcium-Activated Potassium Channels ; physiology ; Muscle, Smooth, Vascular ; cytology ; Myocytes, Smooth Muscle ; physiology ; Renin-Angiotensin System

OBJECTIVETo investigate renal artery injury caused by Kawasaki disease (KD).

METHODSForty-three children with KD were enrolled in the study. According to the blood pressure in the acute stage, these children were classified into normal blood pressure subgroup and increased blood pressure subgroup. Eighteen children with fever caused by acute upper respiratory tract infection were enrolled as the control group. The diameter of the origin of the main renal artery, hemodynamic parameters of the main renal artery and the renal interlobar artery, rennin activity, and levels of angiotensin II and aldosterone were compared between groups.

RESULTSDuring the acute stage of KD, both subgroups had a significantly smaller diameter of the origin of the main renal artery, a significantly higher resistance index (RI) of the main renal artery, and a significantly lower end-diastolic velocity (EDV) than the control group (P<0.05).The increased blood pressure subgroup had a significantly lower EDV of the interlobar artery than the normal blood pressure subgroup, a significantly higher RI than the normal blood pressure subgroup and the control group, as well as a significantly higher rennin activity and significantly higher levels of angiotensin II and aldosterone than the normal blood pressure subgroup (P<0.05). A significantly increased EDV and a significantly reduced RI of the renal interlobar artery were observed in the increased blood pressure subgroup in the subacute stage compared with the acute stage (P<0.05).

CONCLUSIONSKD may cause renal artery injury and early hemodynamic changes, resulting in a transient increase in blood pressure in some patients.

Blood Flow Velocity ; Blood Pressure ; Child, Preschool ; Female ; Humans ; Infant ; Male ; Mucocutaneous Lymph Node Syndrome ; physiopathology ; Renal Artery ; physiopathology ; Renin-Angiotensin System ; physiology ; Vascular Resistance

The present study was aimed to investigate the roles of renal sympathetic nerve and oxidative stress in the development of foot shock-induced hypertension. Ninety rats were divided into 6 groups (the number of each group was 15): control group, foot shock group, denervation of renal sympathetic nerve group, denervation of renal sympathetic nerve + foot shock group, Tempol treatment + foot shock group, denervation of renal sympathetic nerve + Tempol treatment + foot shock group. Rats were received electrical foot shock for 14 days (2-4 mA, 75 V, shocks of 50-100 ms every 30 s, for 4 h each session through an electrified grid floor every day). Renal sympathetic ablation was used to remove bilateral renal sympathetic nerve in rats (rats were allowed to recover for one week before the beginning of the foot shock procedure). The antioxidant Tempol was injected intraperitoneally at 1 h before foot shock. Systolic blood pressure was measured at 1 h after foot shock on day 0, 3, 7, 10 and 14. Contents of thiobarbituric acid reactive substance (TBARS), renin, angiotensin II (AngII) and glutathione peroxidase (GSH-Px) in plasma were measured by ELISA after 14-day foot shock. The results showed that systolic blood pressure of foot shock group was significantly increased (P < 0.05) compared with that of control group from day 7 to day 14 of foot shock. Denervation of renal sympathetic nerve and/or Tempol treatment significantly reduced the increase of systolic blood pressure induced by foot shock. Levels of TBARS, renin and AngII in plasma were increased significantly in foot shock group compared with that of control group (P < 0.05). Plasma GSH-Px concentration was decreased in foot shock group rats compared with that of control group (P < 0.05). Denervation of renal sympathetic nerve and/or tempol treatment significantly reduced the increase in TBARS, renin, AngII levels induced by foot shock in comparison with that of foot shock group (P < 0.05), but had no effects on the reduction of GSH-Px concentration. The results suggest that renal sympathetic nerve may play an important role in the development of foot shock-induced hypertension, and renal sympathetic nerve may influence oxidative stress and directly or indirectly activate renin-angiotensin-aldosterone system, so the foot shock-induced high blood pressure may be maintained and hypertension may therefore be produced.
Animals ; Antioxidants ; pharmacology ; Blood Pressure ; Cyclic N-Oxides ; pharmacology ; Denervation ; Electric Stimulation ; Hypertension ; physiopathology ; Kidney ; innervation ; Oxidative Stress ; Rats ; Renin-Angiotensin System ; Spin Labels ; Sympathetic Nervous System ; physiology

Leptin is a protein hormone produced mainly by obese gene and secreted by adipose tissue and exerts the biological effects through leptin receptors. With the progress in research on the function and receptor signal transduction related leptin and leptin resistance, it has been found that leptin is associated with the development and progression of many cardiovascular diseases, such as hypertension and left ventricular hypertrophy. Some studies have reported that leptin resistance is the pathologic basis for a variety of cardiovascular diseases. This paper will briefly review the advances in the study of correlation between leptin and hypertensive-left ventricular hypertrophy (HLVH), focusing on the relationship between leptin and various factors related to HLVH, such as sympathetic nervous system, renin angiotensin aldosterone system, growth factors, inflammatory factors and insulin resistance.
Adipose Tissue ; Cardiovascular Diseases ; Humans ; Hypertension ; Hypertrophy, Left Ventricular ; Insulin Resistance ; Leptin ; physiology ; Receptors, Leptin ; Renin-Angiotensin System ; Sympathetic Nervous System

Vitamin D is essential for maintaining calcium and phosphate homeostasis, and vitamin D analogues have been prescribed to treat osteoporosis and hyperparathyroidism. Emerging evidence suggests that cardiovascular and chronic kidney diseases are closely associated with vitamin D deficiency resulting from either decreased sunshine exposure or inadequate intake. Vitamin D is through stimulating vitamin D receptor to form a transcriptional complex with cofactors to modulate approximately 3% gene transcription. For example, renin, matrix metalloprotease, and tumor necrosis factor-α are regulated by vitamin D. Both experimental and clinical studies support the health benefits of vitamin D in the cardiovascular system, and such benefits include protecting cardiac function, lowering blood pressure, improving endothelial function, inhibiting oxidative stress, and reducing the activity of renin-angiotensin system. This article will briefly review the cardiovascular benefits of vitamin D and its bioactive analogues and discuss the novel cellular and molecular mechanisms accounting for cardiovascular protection.
Blood Pressure ; Calcium ; physiology ; Cardiovascular Diseases ; physiopathology ; Cardiovascular Physiological Phenomena ; Endothelium, Vascular ; physiology ; physiopathology ; Humans ; Oxidative Stress ; Receptors, Calcitriol ; physiology ; Renin-Angiotensin System ; Vitamin D ; analogs & derivatives ; physiology ; Vitamin D Deficiency ; physiopathology

OBJECTIVETo review the advances of studies on vitamin D receptor and its role in the pathogenesis of diabetic nephropathy.

DATA SOURCESA comprehensive search of the PubMed literatures without restriction on the publication date was carried out using keywords such as vitamin D receptor and diabetic nephropathy.

STUDY SELECTIONArticles related to vitamin D receptor and diabetic nephropathy were selected and carefully analyzed.

RESULTSThe ligands as well as construction and tissue distribution of vitamin D receptor were summarized. Pathogenesis of diabetic nephropathy was analyzed. The mechanisms underlying the renoprotective role of vitamin D receptor including inhibition of renin-angiotensin system, anti-inflammation, anti-fibrosis and the reduction of proteinuria were reviewed. Mounting evidences from animal and clinical studies have suggested that vitamin D therapy has beneficial effects on the renal systems and the underlying renoprotective mechanisms of the vitamin D receptor-mediated signaling pathways is a hot research topic.

CONCLUSIONOur study suggests that vitamin D receptor has a great potential for preventing the progression of diabetic nephropathy via multiple mechanisms.

Animals ; Diabetic Nephropathies ; metabolism ; Humans ; Proteinuria ; metabolism ; Receptors, Calcitriol ; metabolism ; Renin-Angiotensin System ; physiology

It is not well described the pathophysiology of renal injuries caused by a high salt intake in humans. The authors analyzed the relationship between the 24-hr urine sodium-to-creatinine ratio (24HUna/cr) and renal injury parameters such as urine angiotensinogen (uAGT/cr), monocyte chemoattractant peptide-1 (uMCP1/cr), and malondialdehyde-to-creatinine ratio (uMDA/cr) by using the data derived from 226 hypertensive chronic kidney disease patients. At baseline, the 24HUna/cr group or levels had a positive correlation with uAGT/cr and uMDA/cr adjusted for related factors (P<0.001 for each analysis). When we estimated uAGT/cr in the 24HUna/cr groups by ANCOVA, the uAGT/cr in patients with > or =200 mEq/g cr was higher than in patients with <100 mEq/g cr (708 [95% CI, 448-967] vs. 334 [95% CI, 184-483] pg/mg cr, P=0.014). Similarly, uMDA/cr was estimated as 0.17 (95% CI, 0.14-0.21) pM/mg cr in patients with <100 mEq/g cr and 0.27 (95% CI, 0.20-0.33) pM/mg cr in patients with > or =200 mEq/g cr (P=0.016). During the 16-week follow-up period, an increase in urinary sodium excretion predicted an increase in urinary angiotensinogen excretion. In conclusion, high salt intake increases renal renin-angiotensin-system (RAS) activation, primarily, and directly or indirectly affects the production of reactive oxygen species through renal RAS activation.
Adult ; Aged ; Angiotensinogen/urine ; Chemokine CCL2/urine ; Creatine/urine ; Demography ; Female ; Follow-Up Studies ; Humans ; Hypertension/complications ; Male ; Malondialdehyde/urine ; Middle Aged ; Reactive Oxygen Species/*metabolism ; Renal Insufficiency, Chronic/complications/*pathology ; Renin-Angiotensin System/*physiology ; Sodium, Dietary/*urine ; Urine Specimen Collection