Neural pathways from the lamina terminalis influencing cardiovascular and body fluid homeostasis

1. The lamina terminalis, a region of the brain with a high concentration of angiotensin AT1 receptors, consists of three distinct nuclei, the median preoptic nucleus, the subfornical organ and organum vasculosum of the lamina terminalis (OVLT). These latter two regions lack a blood-brain and detect changes in plasma angiotensin (Ang) II concentration and osmolality. 2. Efferent neural pathways from the lamina terminalis to the hypothalamic paraventricular and supraoptic nuclei mediate vasopressin secretion in response to plasma hypertonicity and increased circulating levels of AngII. 3. Studies using the neurotropic virus pseudorabies, which undergoes retrograde transynaptic neuronal transport following injection into peripheral sites, show that neurons in the lamina terminalis have efferent polysynaptic neural connections to the peripheral sympathetic nervous system. Some of these neurons have been shown to have polysynaptic connections to the kidney and to express AT1 receptor mRNA. We propose that circulating AngII acts at AT1 receptors in the subfornical organ and OVLT to influence the sympathetic nervous system. It is likely that the neural pathway subserving this influence involves a synapse in the hypothalamic paraventricular nucleus. 4. The lamina terminalis may exert an inhibitory osmoregulatory influence on renin secretion by the kidney. This osmoregulatory influence may be mediated by inhibition of renal sympathetic nerve activity and appears to involve a central angiotensinergic synapse. 5. The lamina terminalis exerts an osmoregulatory influence on renal sodium excretion that is independent of the renal nerves and is probably hormonally mediated.     

Endothelin in the central control of cardiovascular and respiratory functions

1. Exogenously administered endothelin (ET) modulates the activity of cardiovascular and respiratory neurons in the central nervous system (CNS) and, thus, affects arterial blood pressure (ABP) and ventilation. However, a physiological role(s) for endogenous ET in the CNS has not been elucidated. To address this question, we examined ABP and ventilation in mutant mice deficient in ET-1, ETA and ETB receptors and endothelin-converting enzyme-1, which were made by gene targeting. 2. Respiratory frequency and volume was measured in mice by whole body plethysmography when animals breathed normal room air and hypoxic and hypercapnic gas mixtures. A few days after respiratory measurements, a catheter was implanted into the femoral artery under halothane anaesthesia. On the following day, the ABP of awake mice was measured through the indwelling catheter and heart rate was calculated from the ABP signal. After 2 h ABP measurement, arterial blood was collected through the catheter and pH and the partial pressures of O2 and CO2 were measured by a blood gas analyser. 3. Compared with corresponding controls, the mean (+/- SEM) ABP in ET-1+/- and ETB-deficient mice was significantly higher (118 +/- 2 vs 106 +/- 3 mmHg for ET-1+/- (n = 22) and ET-1+/+ (n = 17) mice, respectively; 127 +/- 3 vs 109 +/- 4 mmHg for ETB-/s (n = 9) and ETB+/s (n = 9) mice, respectively; P < 0.05 for both). In ET-1+/- mice, PCO2 tended to be higher and PO2 was significantly lower than corresponding values in ET-1+/+ mice. Under resting conditions, there was no significant difference in respiratory parameters between mutants and their corresponding controls. However, reflex increases of ventilation to hypoxia and hypercapnia were significantly attenuated in ET-1+/-, ET-1-/- and ETA-/- mice. 4. In another series of experiments in ET-1+/- mice, we found that sympathetic nerve activity (SNA) was augmented and reflex excitation of phrenic nerve activity (PNA) in response to hypoxia and hypercapnia was blunted. Attenuation of the reflex PNA response to hypercapnia was also observed in the medulla-spinal cord preparation from ET-1-/- mice. 5. Elevation of ABP in ETB-deficient mice was most likely due to a peripheral mechanism, because SNA and respiratory reflexes were not different from those in control animals. 6. We conclude that endogenous ET-1 plays an important role in the central neural control of circulation and respiration and that ETA receptors mediate this mechanism.     

Copper homeostasis and cuproptosis in cardiovascular disease therapeutics

Copper (Cu) homeostasis is gaining increasing attention in human health as both Cu overload and deficiency evokes pathological changes including cardiovascular diseases (CVDs). Cu supplementation, nanocarriers, and chelators have all exhibited therapeutic promise in some human diseases, although how Cu dyshomeostasis and cuproptosis, a novel form of regulated cell death, contribute to CVD pathology remains elusive. Here, we discuss Cu dyshomeostasis and the potential role of cuproptosis in various CVDs. We evaluate underlying cellular mechanisms, aiming to provide some insights regarding the utility of targeting Cu dyshomeostasis and cuproptosis as a novel strategy in the management of CVDs.     

Angiotensin and osmoreceptor inputs to the area postrema: role in long-term control of fluid homeostasis and arterial pressure

1. The role of the area postrema (AP) in the long-term control of body fluid homeostasis and arterial pressure under conditions of increased dietary salt intake is reviewed. A model is proposed in which sympathetic nerve activity is suppressed when dietary salt is increased. It is hypothesized that the AP acts as an essential integrative site in the hind-brain for this response. 2. An essential component of the hypothesis is that basal levels of circulating angiotensin II support arterial pressure in animals consuming a normal salt diet by acting on the AP to drive sympathetic nerve activity. This hypothesis is supported by the observation that the long-term hypotensive response to losartan, the AT1 receptor antagonist, is attenuated in AP-lesioned (APx) rats. 3. The role of hepatoportal sodium receptors in signalling the AP about changes in dietary salt intake is discussed. Intragastric hypertonic saline infusion increases portal venous, but not systemic plasma, osmolality and increases Fos-like immunoreactivity in the AP, nucleus tractus solitarius and the supraoptic, paraventricular and lateral parabrachial nuclei. Other studies have shown that stimulation of these receptors decreases renal sympathetic nerve activity. 4. The hypothesis that the AP is critical in long-term control of arterial pressure and body fluid homeostasis under conditions of altered dietary salt intake was studied. The responses of arterial pressure and sodium and water balance to changes in dietary salt intake were measured in intact and APx rats. Contrary to the hypothesis, APx rats did not exhibit impaired regulation of arterial pressure or water balance. However, APx rats did demonstrate an impaired ability to excrete sodium when salt intake was elevated. 5. Based on these observations, it is concluded that the AP is important in the control of sodium balance, but not arterial pressure, when dietary salt intake is altered.     

Changes in cerebrospinal fluid volume and cardiovascular functions induced by intraperitoneal injection of hypertonic glucose solution in rats

The present experiment was undertaken to study the relationship between hemodynamic changes and intracranial hemorrhage induced by intraperitoneal injection of large doses of hypertonic glucose solution in rats. A fifty per cent glucose solution was intraperitoneally injected at a volume of 3.5 ml/100 g b.w. into Wistar rats anesthetized with urethanechloralose. The time span from the start of injection to death was expressed in terms of 100% corrected death time (100% DT) for each rat. Saline that was added to the cerebrospinal fluid in the brain ventricle disappeared gradually from 30% DT up to death. Blood colloid osmotic pressure was slightly elevated temporally 5 minutes (7% DT) after intraperitoneal injection of the glucose solution and returned to the former level 5 minutes later. With regard to hemodynamic changes, a decrease in blood pressure and heart rate began to occur between 5-10% DT. Thereafter, blood pressure and heart rate decreased significantly as compared with the pretreatment period, and the plasma levels of both epinephrine and norepinephrine showed sharply increasing curves as time elapsed after the intraperitoneal injection of the hypertonic glucose solution. It was suggested that the decrease in cerebrospinal fluid and the fall in blood pressure were related to the movement of water from the brain and the flow of body fluid into the hypertonic blood plasma which caused an enlargement of the ventricles due to brain reduction and a change in circulating blood volume. However, questions still remain concerning the mechanisms of the marked increase in plasma catecholamines and bleedings which occurred only in the subarachnoideal space and ventricles.     

Cholinergic signaling controls immune functions and promotes homeostasis

Acetylcholine (ACh) was created by nature as one of the first signaling molecules, expressed already in procaryotes. Based on the positively charged nitrogen, ACh could initially mediate signaling in the absence of receptors. When evolution established more and more complex organisms the new emerging organs systems, like the smooth and skeletal muscle systems, energy-generating systems, sexual reproductive system, immune system and the nervous system have further optimized the cholinergic signaling machinery. Thus, it is not surprising that ACh and the cholinergic system are expressed in the vast majority of cells. Consequently, multiple common interfaces exist, for example, between the nervous and the immune system. Research of the last 20 years has unmasked these multiple regulating mechanisms mediated by cholinergic signaling and thus, the biological role of ACh has been revised. The present article summarizes new findings and describes the role of both non-neuronal and neuronal ACh in protecting the organism from external and internal health threats, in providing energy for the whole organism and for the individual cell, controling immune functions to prevent inflammatory dysbalance, and finally, the involvement in critical brain functions, such as learning and memory. All these capacities of ACh enable the organism to attain and maintain homeostasis under changing external conditions. However, the existence of identical interfaces between all these different organ systems complicates the research for new therapeutic interventions, making it essential that every effort should be undertaken to find out more specific targets to modulate cholinergic signaling in different diseases.     

Nitrendipine and the humoral control of sodium homeostasis.

1. Nine healthy volunteers received 10 mg nitrendipine or placebo orally in random order. 2. In the subsequent 5 h urinary sodium excretion was 20% higher after nitrendipine, without any significant difference between the volume of urine excreted after nitrendipine or placebo. Mean blood pressure fell by 5 mm Hg (P less than 0.001), and mean heart rate increased by 5 beats min-1 (P less than 0.01) after nitrendipine but did not change after placebo. 3. These changes were accompanied by a significant elevation in plasma renin activity (P less than 0.001). A fall in plasma aldosterone following placebo appeared to be attenuated by nitrendipine. Plasma noradrenaline increased to a peak 3 h after nitrendipine administration (P less than 0.05) but did not change following placebo. A fall in the excretion of 6-keto PGF1 alpha following placebo was attenuated by nitrendipine. The total excretion of 6-keto PGF1 alpha after nitrendipine was significantly greater (P less than 0.05) than after placebo but not difference in the total excretion of PGE2 was detected. Nitrendipine did not affect urinary kallikrein excretion. 4. The natriuretic action of nitrendipine is not mediated by the kallikrein-kinin system, but may be related to changes in renal prostaglandins.     

Importance of the gut-brain axis in the control of glucose homeostasis

Adult mammals finely match glucose production to glucose utilization, thus allowing glycaemia to be maintained in a physiological range of 0.8-1.2mg/dl whatever the energetic status of the mammal (i.e. fed or fasted, rested or exercised). To accomplish this, peripheral signals originating from the gut 'inform' the central nervous system, which in turn is able to monitor the status of both peripheral glucose stores and ongoing fuel availability. Indeed, both secretion and action of hormones regulating endogenous glucose production and utilization are regulated by the autonomic nervous system. These gut signals are either hormonal (e.g. glucagon-like peptide-1, ghrelin and cholecystokinine) or neuronal (e.g. afferent vagus nerve fibres). Recent data, combined with the development of incretin analogues for treatment of diabetes, highlight the importance of the gut-brain axis, especially glucagon-like peptide-1 and ghrelin, in the control of glucose homeostasis.     

Putative role for apelin in pressure/volume homeostasis and cardiovascular disease

Apelin is a peptide recently isolated from bovine stomach extracts which appears to act as an endogenous ligand for the previously orphaned G-protein-coupled APJ receptor. The apelin gene encodes for a pre-propeptide consisting of 77 amino acids with mature apelin likely to be derived from the C-terminal region as either a 36, 17 or 13 amino acid peptide. Apelin mRNA expression and peptide immunoreactivity has been described in a variety of tissues including gastrointestinal tract, adipose tissue, brain, kidney, liver, lung and at various sites within the cardiovascular system. Apelin is strongly expressed in the heart with expression also present in the large conduit vessels, coronary vessels and endothelial cells. Message expression for the APJ receptor is similarly distributed throughout the brain and periphery, again including cardiovascular tissue. Consistent with this pattern of distribution, apelin and APJ have been shown to exhibit some role in the regulation of fluid homeostasis. In addition, a growing number of studies have reported cardiovascular actions of apelin. Not only has apelin been observed to alter arterial pressure, but the peptide also exhibits endothelium-dependent vasodilator actions in vivo and positive inotropic actions in the isolated heart. Furthermore, differences in apelin and APJ expression have been described in patients with congestive heart failure and circulating levels of apelin are also reported to change in heart failure. Taken together, these studies suggest a role for apelin in pressure/volume homeostasis and in the pathophysiology of cardiovascular disease. As such, manipulation of this peptide system may offer benefit to the syndrome of heart failure with potential clinical applications in humans.     

Research progress on the functions of vitamins in body

Vitamins are natural materials essential for maintaining the normal physical function of the live cells. It has been reportedthat 13 vitamins are needed in our body, included vitamin A, B vitamins (thiamine, riboflavin, niacin, pantothenic acid, pyridoxine, biotin, folic acid and cobalamin), vitamin C, vitamin D, vitamin E and vitamin K. Nowadays, the functions of vitamins have been extensively investigated. The objective of this paper is to summarize the new functions of vitamins, aiming to provide suggestions on the usage of various vitamins in clinical application.     

Effects of azaperone on cardiovascular and respiratory functions in the horse.

1 The butyrophenone tranquilizer, azaperone, was administered intramuscularly, at dose levels of 0.4 and 0.8 mg/kg, to ponies and its effects on cardiovascular and respiratory functions assessed. 2 Arterial blood pH, CO2 tension (PaCO2) and O2 tension (PaO2) remained relatively constant throughout the course of action of azaperone. 3 Azaperone did not modify plasma protein concentration but venous blood packed cell volume and haemoglobin concentration were reduced by 5 to 10% for at least 4 hours. These changes were probably caused by uptake of erythrocytes into the splenic reservoir. 4 Small increases in heart rate occurred for up to 60 min after administration of the drug, and this was followed by a slight bradycardia in some ponies. 5 Azaperone reduced mean arterial blood pressure (MAP) for at least 4 h, by which time its ataractic action was generally no longer apparent. The hypotension was caused, during the early phase of action at least, by a reduction in peripheral resistance, since cardiac output was increased slightly 20 min after its administration. Possible mechanisms underlying the cardiovascular changes are discussed. 6 In spite of reductions in arterial blood O2 content and MAP produced by azaperone, it is likely that tissue oxygenation was adequate, since arterial blood lactate concentrations were not increased.     

内源性大麻素系统对心血管功能的调节作用

内源性大麻素通过受体依赖性和非依赖性途径经一系列细胞内信号传导通路,可发挥多种重要的心血管效应,如舒张血管、降低血压和抑制心肌收缩等。它还参与抗炎、保护内皮细胞的作用。因此,对其作用机制的深入研究在防治高血压、动脉粥样硬化、缺血/再灌注损伤和心衰等心血管疾病中有重要意义。     

The distribution of cefotiam in body fluid

All subjects were patients with malignant tumors on the gastroenterological system and in whose cases there were marked ascites (Table 1). In the study, each patient was subjected to the intravenous drip infusion of CTM 1 g for a period of 1 hour. Samples of peripheral venous blood and ascites were taken 4 times, at 1 hour after completion of infusion, and at 2, 3 and 4 hours. The test samples were kept at -80 degrees C until the CTM contents were determined (Fig. 1). Determination results 1. Blood concentrations of CTM decreased with the passage of time (Fig. 2). 2. There was hardly any difference in the concentration of CTM in ascites between the 1 hour and 4 hour samples. Furthermore, the concentration was maintained which exceeded the MIC against intestinal flora, including Escherichia coli, without Pseudomonas and Bacteroides (Fig. 3, Table 2). 3. The higher serum creatinine levels were the greater the concentration of CTM in blood (Fig. 5). 4. The maximum blood and ascites concentration of CTM indicated a correlation coefficient of 0.809, P less than 0.01 (Fig. 6). These results led to the following conclusions: 1. If 1 hour intravenous drip infusion of CTM 1 g/100 ml is to be carried out against postoperative peritoneal infection, such administration at interval less than 5-hours would not be reasonable. 2. The peritoneal invasion of malignant tumor is not a factor in the inhibition of CTM transition from blood to ascites.     

Involvement of insulin-like growth factor-I in the control of glucose homeostasis

Insulin-like growth factor-I (IGF-I) has significant structural homology with proinsulin. IGF-I binds to insulin receptors, stimulates insulin-like actions and enhances insulin sensitivity. However, because circulating IGF-I is bound to high-affinity binding proteins and has relatively low affinity for insulin receptors, most of its ability to alter insulin sensitivity is mediated indirectly (i.e. through suppression of growth hormone, a known insulin antagonist). Direct effects of IGF-I on insulin actions are tissue specific, occurring principally in skeletal muscle and kidney. Genetic manipulations in experimental mouse models have been used to analyze the role of endogenous IGF-I on insulin action. These studies have shown that suppression of growth hormone is important for enhancing insulin action in the liver and that deletion of the IGF-I receptor in skeletal muscle results in severe insulin resistance. IGF-I also suppresses renal gluconeogenesis, which might contribute to its glucose-lowering actions. In humans, IGF-I enhances insulin sensitivity and lowers blood glucose in patients with either extreme insulin resistance or type 2 diabetes. It also decreases insulin requirement in patients with insulin-deficient diabetes. Taken together, these findings suggest that IGF-I is functioning coordinately with insulin to regulate glucose homeostasis.     

Automating the purchasing and inventory control functions

Factors involved in computerizing the purchasing and inventory control functions in hospital pharmacies are described. When initiating an automated purchasing and inventory control system, a feasibility study should first be conducted to determine the extent of automation needed to develop a cost-effective system. The design of the system will depend on the extent to which the department of materials management is involved with other hospital departments. The advantages and disadvantages of decentralized versus centralized systems are discussed, and criteria for selecting hardware and software vendors are presented. A return-on-investment analysis should be performed to validate the benefits or savings expected from implementing the new automated system. Factors to consider during implementation of the new system and future developments affecting purchasing and inventory control systems, such as bar coding, are discussed. With the current concern about rapidly rising health-care costs and the need to enhance productivity, the development and implementation of automated purchasing and inventory control systems are important strategies for institutions to pursue now.