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The autonomic nervous system, which consists of sympathetic and parasympathetic nerves, plays an important role in the regulation of various functions of body organs. Recent studies have reported that vagal afferents that transmit information from the periphery to the brain function as an important signal pathway for dissemination of details regarding nutritional status, as well as the cardiovascular system and inflammation. In this review, we describe the measurement analysis of vagal nerve activity in mice using an in vivo electrophysiological method and account for the role and mechanism of action of vagal nerves in homeostasis.

Parasympathetic nervous system activity dominates during non-rapid eye movement (REM) sleep, whereas the sympathetic nervous system is dominant during REM sleep. The balance between the sympathetic and parasympathetic nervous systems reduces the heart rate and blood pressure during non-REM sleep and increases these parameters during REM sleep and wakefulness. Heart rate variability analysis, a non-invasive method of autonomic nervous system analysis, may be useful in screening for obstructive sleep apnea and also to predict orthostatic hypotension secondary to autonomic disturbances in patients with REM sleep behavior disorder.

Angiotensin II (Ang II) is an intrinsic peptide having strong vasopressor effects, and thus, it plays an important role in the physiological regulation of blood pressure. The vasopressor effects of Ang II include direct contraction of myocardium and vascular smooth muscles (SMs) along with aldosterone-mediated sodium retention. In addition, indirect vascular contractions induced by noradrenaline (NA), the release of which is mediated through Ang II receptor type 1 (AT 1 ) existing at the sympathetic nerve terminals (SNTs), also contribute to the vasopressor effects of Ang II. Stimulation of NA release from SNTs by Ang II also occurs in the myocardium leading to an increase in heart rate and cardiac contraction. Furthermore, Ang II enhances the contractions of non-vascular SMs, such as vas deferens, through induction of NA release from the SNTs. We have found that Ang II attenuated vagus nerve stimulation-induced bradycardia in a losartan-sensitive manner. This suggests that Ang II attenuates vagus nerve stimulation-induced bradycardia by inhibiting acetylcholine (ACh) release from the parasympathetic nerve terminals (PNTs) through activation of the AT 1 receptor. Ang II was also reported to attenuate the release of ACh from the PNTs in SMs, such as stomach and airway, thus suppressing their contractile functions. There are, however, conflicting reports of the effects of Ang II on parasympathetic nerve-mediated contractile regulation of SMs. In this review, we have highlighted the relevant research articles including our experimental reports on the regulation of sympathetic and parasympathetic nerve-mediated excitation and contraction by Ang II along with the future prospects.

Selective sodium glucose transporter-2 inhibitor (SGLT2i) treatment promotes urinary glucose excretion, thereby reducing blood glucose as well as body weight. However, only limited body weight reductions are achieved with SGLT2i administration. Hyperphagia is reportedly one of the causes of this limited weight loss. However, the effects of SGLT2i on systemic energy expenditure have not been fully elucidated. We investigated the acute effects of dapagliflozin, an SGLT2i, on systemic energy expenditure in mice. Eighteen hours after dapagliflozin administration, oxygen consumption and brown adipose tissue (BAT) expression of ucp1, a thermogenesis-related gene, were significantly decreased as compared with those after vehicle administration. In addition, dapagliflozin significantly suppressed norepinephrine (NE) turnover in BAT and c-fos expression in the rostral raphe pallidus nucleus (rRPa), which contains the sympathetic premotor neurons responsible for thermogenesis. These findings indicate that the dapagliflozin-mediated acute decrease in energy expenditure involves a reduction in BAT thermogenesis via decreased sympathetic nerve activity from the rRPa. Furthermore, common hepatic branch vagotomy abolished the reductions in ucp1 expression, NE contents in BAT, and c-fos expression in the rRPa. In addition, alterations in hepatic carbohydrate metabolism, such as decreases in glycogen contents and upregulation of phosphoenolpyruvate carboxykinase, occurred prior to the suppression of BAT thermogenesis, e.g., 6 h after dapagliflozin treatment. Collectively, these results suggest that SGLT2i acutely suppresses energy expenditure in BAT via regulation of an interorgan neural network consisting of the common hepatic vagal branch and sympathetic nerves.

Many patients with type 2 diabetes mellitus develop hypertension, although the actual mechanism remains unknown. To clarify possible mechanisms of hypertension development in diabetes, this study investigated the acute or chronic influence of hyperinsulinemia and/or hyperglycemia on the function of perivascular nerves, which play a critical role in vascular tone regulation. Acute hyperinsulinemia in euglycemic pithed rats, which had no autonomic flow, significantly augmented adrenergic nerve-mediated pressor responses and inhibited calcitonin gene-related peptide (CGRP)-containing (CGRPergic) nerve-mediated depressor responses. To increase blood glucose levels without changing serum insulin levels, pithed rats were treated with octreotide. In this model, acute hyperglycemia produced only marked enhancement of adrenergic nerve-mediated vasoconstriction. Chronic hyperinsulinemia in insulin resistance model rats caused significant increases in the function and distribution of perivascular sympathetic nerves and decreases in those of perivascular CGRPergic nerves, resulting in the development of hypertension (insulin resistance-induced hypertension). Treatment with pioglitazone or functional foods with an insulin resistance-improving effect prevented the development of insulin resistance-induced hypertension. The present studies suggest that acute and chronic hyperinsulinemia reduces vasodilator function of perivascular CGRPergic nerves and enhances the vasoconstrictor function of perivascular adrenergic nerves, leading to the development of hypertension. The results also indicate that hyperinsulinemia and hyperglycemia may have a crucial role in the alteration of neuronal vascular tone regulation.

Bone homeostasis is maintained by bone formation and bone resorption. The traditional view of bone metabolism as a primarily endocrine regulation has been expanded in recent years following the identification of nervous system controlling bone metabolism. Especially, sympathetic and parasympathetic nervous system regulates bone formation and bone resorption. In addition, sensory nervous system also has been shown to be involved in the regulation of bone homeostasis. These studies demonstrated that nervous system is closely related to bone remodeling.

Human sweating is functionally classified into thermoregulatory, emotional, and gustatory sweating. Several central and peripheral nervous structures are involved in the sudomotor systems. Therefore, an anatomical understanding of the sudomotor systems and clinical evaluation of its function are useful for regional neurological diagnose. In addition, some neurological diseases may present characteristic abnormalities of sweating. This systematic review summarizes the anatomy, physiology, and symptomatology of sweating as well as the clinical characteristics of abnormal sweating in neurological disorders.

We sometimes make decisions relying not necessarily on deliberative thoughts but on intuitive and emotional processes in uncertain situations. The somatic marker hypothesis proposed by Damasio argued that interoception, which means bodily responses such as sympathetic activity, can be represented in the insula and anterior cingulate cortex and can play critical roles in decision-making. Though this hypothesis has been criticized in its theoretical and empirical aspects, recent studies are expanding the hypothesis to elucidate multiple bodily responses including autonomic, endocrine, and immune activities that affect decision-making. In addition, cumulative findings suggest that the anterior insula where the inner model of interoception is represented can act as an interface between the brain and body in decision-making. This article aims to survey recent findings on the brain-body interplays underlying decision-making, and to propose hypotheses on the significance of the body in decision-making.

Left ventricular (LV) function is usually measured by imaging modalities such as echocardiography under static conditions in patients with dilated cardiomyopathy (DCM). However, some studies have reported that LV contractile function at rest is not reliable for assessment of the reversibility of LV contraction. Therefore, it is important to evaluate LV functional response under dynamic conditions by use of pharmacological as well as exercise stress (contractile reserve). In our studies, LVdP/dtmax was measured at rest and under dobutamine stress using a pigtail catheter with a high-fidelity micromanometer placed into the left ventricle in DCM patients. deltaVdP/dtmax as an index of myocardial contractile reserve was defined as the percentage increase in LVdP/dtmax induced by dobutamine infusion. Firstly, deltaLVdP/dtmax was correlated with peak oxygen consumption by cardiopulmonary exercise testing. In addition, impaired deltaLVdP/dtmax was associated with unfavorable prognosis. Secondly, reduced deltaLVdP/dtmax was associated with an increased washout rate evaluated by myocardial 123I-MIBG and 99mTc-MIBI scintigraphy. Finally, this residual contractile reserve was related to molecular remodeling caused by overactivation of the sympathetic nerve system in DCM patients. This review focused on the current status of contractile reserve with our findings, including procedures for evaluating contractile reserve, clinical implications, and molecular biological significance.

Bone formation and maintenance are sophisticatedly orchestrated through a well-organized and highly regulated mechanism by two distinct cell types; bone-forming osteoblast and bone-resorbing osteoclast. It has been previously established that the adipocyte-derived hormone leptin regulates bone metabolism through the central nervous system and the sympathetic nervous system. We recently identified the osteoblast as the principal cell type in which the sympathetic tone could signal to regulate bone mass by generating and analyzing the cell specific adrenergic receptor deletion mice. The fact that adipocyte-derived hormone regulates bone metabolism implies that the skeleton might exert a feedback control of glucose metabolism. We then revealed that the skeleton acts as an endocrine regulator of energy metabolism through the osteoblast-specific secreted molecule osteocalcin that activates insulin secretion by pancreatic β-cells, insulin sensitivity in fat, liver, and muscle. Moreover, we have recently reported that the sympathetic tone into osteoblast is a pivotal mediator of leptin regulation of insulin secretion by regulating osteocalcin bioactivity. This unexpected functional cross talk between fat, nervous systems, and skeleton illustrates the importance of the skeleton for the regulation of major physiological functions such as glucose homeostasis in vertebrates.

It has been believed that bone is controlled by local environment through the action of hormone and cytokines, independently of other organs. However, the discovery that leptin regulates bone formation through the central nervous system shed light on a new regulatory system of bone metabolism, i.e., neuronal control. Moreover, recent discovery that osteocalcin regulates glucose metabolism and fertility clearly demonstrated that bone forms a regulatory network of metabolism, together with other organs.

Recent advances of molecular genetics made it possible to generate genetically-modified mice. Furthermore, the discovery and application of Cre-loxP recombination system into mouse genetics led to study the function of a gene in a tissue-specific manner. Analyses of these mutant mice advanced our understanding of the molecular physiology and pathophisiology of skeletal tissue.

There is increasing evidence for a contribution of serotonin to the regulation of bone metabolism. In the periphery, gut derived serotonin (GDS) regulates osteoblast proliferation and bone formation. In the brain, brain derived serotonin regulates bone mass through sympathetic nervous system. In addition, inhibition of GDS biosynthesis can treat osteoporosis in ovariectomized rodents by increasing bone formation. The emerging evidence has suggested that inhibiting GDS biosynthesis could become a new anabolic treatment for osteoporosis in humans.

Heat stress is a major environmental factor which perturbs working in safety. In humans, heat stress increases the occurrence of orthostatic syncope and induces marked reductions in orthostatic tolerance. Several mechanisms, including an altered baroreflex responsiveness in heart rate (HR) and peripheral vasomotion, are involved in orthostatic intolerance. In the present review, we discuss the effects of heat stress on the baroreflex function in controlling HR and peripheral vasomotion. The present findings from human studies suggest that (1) heat stress slows the arterial baroreflex responses in HR and peripheral vasomotion and decreases the responses to rapid hypotensive stimulation, (2) heat stress reduces the sensitivity of the spontaneous baroreflex control of HR during orthostasis but not during supine rest, (3) central blood volume decreases with increasing skin blood flow and the sensitivity of the integrative baroreflex control of total peripheral vascular resistance is reduced in heat-stressed humans, and (4) the reduced baroreflex sensitivity of total peripheral vascular resistance may be partly due to the reduction in skin vasoconstrictor response. The altered baroreflex responsiveness in HR and peripheral vasomotor control as well as central hypovolemia are related to orthostatic intolerance in a hot environment.

It has been demonstrated that osteocalcin, osteoblast-secreted molecule, regulates energy metabolism through acting on pancreatic β-cells and adipocytes, while it has been established that the adipocyte-derived hormone leptin regulates bone metabolism through central nervous system and sympathetic nervous system. Recently, it has been reported that sympathetic tone into osteoblasts is a mediator of leptin regulation of insulin secretion. These functional relationship between bone and multiple organs illustrates the pivotal role of the skeleton in the regulation of our major physiological functions including energy metabolism.

The relationship between bone and nervous system has been considered based on clinical observations such as Reflex Sympathetic Dystrophy (RSD) or ectopic bone formation associated with spinal cord injury. Sympathtic nervous tone has been reported to control both bone formation and bone resorption. Unloading induces bone loss due to an increase in bone resorption and decrease in bone formation. Both of these two arms are shown to be influenced by sympathetic tone. In addition, cannabinoid receptor has been observed to be involved in regulation of bone mass. Psychiatric diseases such as depression has also been suggested to linked to the alteration in the levels of bone mass. These observations together point to importance of the relationship between bone mass and nervous system.

Propolis is known to have abundant bioactive constituents and a variety of biological activities. To investigate the effect of Brazilian propolis on insulin resistance, 10-week-old Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a non-insulin-dependent type 2 diabetic model, were treated for 4 weeks with propolis (100 and 300 mg/kg, p.o.) or vehicle (control). Propolis treatment significantly decreased the plasma levels of insulin and insulin resistance index (Homeostasis Model Assessment-Insulin Resistance; HOM-IR), without affecting blood glucose levels and tended to lower systolic blood pressure compared with the control. In isolated and perfused mesenteric vascular beds of OLETF rats, propolis treatment resulted in significant reduction of sympathetic nerve-mediated vasoconstrictor response to periarterial nerve stimulation (PNS) and tended to increase calcitonin gene-related peptide (CGRP) nerve-mediated vasodilator response to PNS compared with in vehicle-treated OLETF rats. However, propolis treatment did not significantly affect the vasoconstrictor and vasodilator response to noradrenaline, CGRP, acetylcholine, and sodium nitroprusside. These results suggest that propolis could be an effective and functional food to prevent development of insulin resistance.

The involvement of insulin/IGF-1 signals and leptin signals in spinal ligament cells was investigated using Zucker fatty rats (fa/fa) that carry mutation of the leptin receptor gene (fa) and monosodium glutamate-treated (MSG) rats that present obesity due to destruction of the hypothalamic ventromedial nucleus. Zucker fatty rats (ZFR) , that have a with functional abnormality of leptin receptors are a spontaneous model of ossification of the posterior longitudinal ligament that develops sympathetic nerve hypoactivity. (insulin/IGF-1 signals) IRS-1-positive cells, IRS-1 protein were eminent by detected in the cartilage endplate and the enthesis region in ZFR group. On the other hand, IRS-2-positive cells were slightly less in the ZFR group than in the MSG and control groups. The results suggest that IRS-1-mediated signaling for cell proliferation was enhanced in ZFR, which may explain the ossification of the posterior longitudinal ligament. (Leptin signals) We investigated the effects of leptin on the spinal ligament in ZFR histopathologically and immunohistochemically. Since Ob-R does not play any role due to functional abnormality in ZFR, the direct involvement of leptin in ligament ossification may be slight in ZFR. beta(2)AR expression in the stage preceding ligament ossification was confirmed, suggesting that ossification of the spinal ligament may be inhibited by sympathetic nerve stimulation in ZFR.

Skin sympathetic nerve activity (SSNA) is microneurographically recorded from the skin nerve fascicle in the peripheral nerves. It is characterized by the following features: 1) irregular, pulse asynchronous, burst activity with respiratory variation, 2) burst activity followed by vasoconstriction and/or sweating, 3) elicited by mental stress and arousal stimuli, e.g., sound, pain, electric stimulation, 4) burst with longer duration as compared with sympathetic outflow to muscles, and 5) burst activity following sudden inspiratory action. It comprises vasoconstrictor (VC) and sudomotor(SM) activity, as well as vasodilator (VD) activity. VC and SM discharge independently, whereas VD is the same activity with different neurotransmission. The VC and SM are differentiated by effector response, e.g., laser Doppler flowmetry and skin potential changes. SSNA function in thermoregulation in the human body; however it is also elicited by mental stress. SSNA is the lowest at thermoneutral ambient temperature (approximately 27 degrees C), and is enhanced in the pressence of ambient warm and cool air. The burst amplitude is well-correlated to both skin blood flow reduction rate or sweat rate change. The clinical application of SSNA comprises the following: 1) clarification of sweating phenomenon, 2) clarification and diagnosis of anhidrosis, 3) clarification and diagnosis of hyperhidrosis, 4) clarification of thermoregulatory function and diagnosis of thermoregulatory disorder, 5) clarification of pathophysiology and diagnosis of vascular diseases, e.g., Raynaud and Buerger diseases. 6) clarification of the relation between cognitive function and SSNA and 7) determination of pharmacological effect attributable to change in neuroeffector responses.

Microneurography is an electrophysiological method that directly records impulse traffic from human peripheral nerves by using metal microelectrodes. This method enables the recording of identified postganglionic sympathetic efferent neural traffic leading to the skeletal muscles (muscle sympathetic nerve activity) and skin (skin sympathetic nerve activity), as well as myelinated and unmyelinated afferent nerve impulses from the sensory receptors in skeletal muscles (muscle spindles, Golgi tendon organs, and nociceptors) and skin (skin mechanoreceptors and noci-thermoceptors). The clinical applications of sympathetic microneurography are useful for the elucidation of the neural mechanisms of abnormal blood pressure control and thermoregulation. Sympathetic microneurography is also used in space medicine to elucidate changes in sympathetic neural traffic during and after exposure to simulated microgravity and spaceflight. The clinical applications of sensory microneurography are useful to clarify the neural mechanisms underlying abnormalities in muscle and skin sensation and those in sensory motor control. Microstimulation by using the microneurography technique can also be used to determine the peripheral sensory, sympathetic, and motor nerve functions.

The role of nitric oxide (NO)-containing nerves in adrenergic neurotransmission in hypertension was studied in mesenteric resistance arteries without endothelium in 2-kidney-1-clip renal hypertensive rats (2K-1C RHR) and sham-operated normotensive rats (Sham-R). Mesenteric vascular beds isolated from 2K-1C RHR and Sham-R were perfused with Krebs solution and changes in perfusion pressure were measured with a pressure transducer. Perfusion of a NO synthase inhibitor, N-omega-nitro-L-arginine methyl ester (L-NAME), markedly augmented vasoconstrictor responses to periarterial nerve stimulation (PNS) without affecting vasoconstriction induced by exogenously injected noradrenaline. L-NAME significantly increased the neurogenic release of NA evoked by PNS in both 2K-1C RHR and Sham-R preparations. The facilitatory effect of L-NAME based on the inhibition of NO production in 2K-1C RHR was less than that in Sham-R. These results suggest that the function of NO-containing nerves, which presynaptically inhibit adrenergic neurotransmission, is decreased in the renovascular hypertensive model rat.

Recent clinical studies demonstrated that transient postprandial hyperglycemia and hyperinsulinemia may contribute to the development of hypertension. Therefore, we investigated influence of acute hyperglycemia and/or hyperinsulinemia induced by glucose or insulin infusion on neuronal and humoral control of vascular tone in rats. Euglycemic male Wistar rats were pithed under anesthesia and arterial blood pressure was measured. Changes in vascular responses to spinal cord stimulation (SCS) and intravenous bolus injections of noradrenaline, angiotensin II, calcitonin gene-related peptide (CGRP), acetylcholine and sodium nitroprusside (SNP) were studied by infusing various concentration of glucose or insulin. Continuous glucose infusion, which increased both blood glucose and serum insulin levels, significantly augmented adrenergic nerve-mediated pressor responses to SCS without affecting injection of pressor responses to noradrenaline or angiotensin II. In pithed rats with artificially increased blood pressure and blockade of autonomic outflow, glucose infusion attenuated CGRPergic nerve-depressor responses to SCS without affecting depressor responses to injection of CGRP, acetylcholine or SNP. In pithed rats treated with octreotide, which increased blood glucose without increasing serum insulin levels, glucose infusion caused only significant augmentation of adrenergic nerve-mediated pressor responses. Combined infusion of insulin and glucose, which resulted in increased serum insulin levels with euglycemic, significantly augmented adrenergic nerve-mediated pressor responses and attenuated CGRPergic nerve-mediated depressor responses. The present results suggest that acute hyperglycemia and hyperinsulinemia increases adrenergic nerve-mediated vasoconstriction, which is partly associated with the blunted CGRPergic nerve function, and that plasma insulin concentration associated with hyperglycemia may be responsible for alteration of neuronal vascular regulation.

The discovery of central control of bone remodeling by leptin and sympathetic nervous system shed light on a novel mechanism of bone remodeling. Furthermore, other neuropeptides, such as cocaine- and amphetamine-regulated transcript or neuromedin U, have been shown to be intimately involved in bone remodeling.

The purpose of this study was to examine changes in the control of sweating by heat acclimation by using frequency of sweat expulsion (Fsw), an index of central sudomotor activity. Eight healthy young volunteers underwent a six-day heat acclimation program [a total of 80-min exercise at 50% peak rate of oxygen consumption in the heat (36 degrees C)]. In the days before and after the heat acclimation program, we examined the local sweating rate (SR) at the chest and forearm, Fsw and esophageal temperature (Tes) during whole body heating using a water-perfused suit. Heat acclimation decreased (P < 0.01) the Tes thresholds for initiation of chest and forearm sweating. Heat acclimation did not change the slopes of the SR at either site or Fsw versus Tes during heating, but shifted the slopes to a lower Tes. Heat acclimation did not change the slopes of the SR at either site versus Fsw, and the SR values at a given Fsw were similar between before and after heat acclimation. These findings suggest that short-term heat acclimation modulates central sudomotor mechanisms, decreasing the temperature threshold for sweating. We did not find a significant change in the peripheral mechanism for sweating by the heat acclimation program.

Royal jelly (RJ) is known to have abundant nutritional properties and a variety of biological activities. To investigate the effects of RJ on insulin resistance, 10-week-old Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a type 2 diabetic model, were treated for 4 weeks with RJ (10, 30, and 300 mg/kg, p.o.). RJ treatment tended to decrease systolic blood pressure and significantly decreased serum levels of insulin and the Homeostasis Model Assessment ratio, an index of insulin resistance. In isolated and perfused mesenteric vascular beds of OLETF rats, RJ treatment resulted in significant reduction of the sympathetic nerve-mediated vasoconstrictor response to periarterial nerve stimulation (PNS) and potentiation of the calcitonin gene-related peptide (CGRP) nerve-mediated vasodilator response to PNS, compared with that in untreated OLETF rats. However, RJ treatment did not significantly affect norepinephrine-induced vasoconstriction and CGRP-induced vasodilation. These results suggest that RJ could be an effective and functional food to prevent the development of insulin resistance.

Gastroesophageal reflux disease can be divided into two groups, reflux esophagitis and non-erosive reflux disease, according to the presence of esophageal mucosal breaks. Almost all the reflux esophagitis with mucosal breaks are caused by the pathological reflux of acidic gastric contents to esophagus. Therefore, drugs that suppress gastric acid secretion effectively control reflux symptoms. On the other hand, almost 40% of nonerosive reflux disease are not caused by the reflux of gastric acid but by acid-unrelated mechanisms. Therefore, administration of proton pump inhibitors cures reflux symptom of only 50% of cases with non-erosive reflux diseases. The multi-pathogenesis of nonerosive reflux disease should be considered for the treatment of patients with reflux symptoms.

Orexins were initially reported as regulators of food intake. More recent reports suggest that they might play roles in the multiple functions of neuronal systems, causing medical conditions such as narcolepsy, a sleep disorder. Orexins and their receptors (OX1R and OX2R) are distributed in the neural tissue and brain regions involved in the autonomic and neuroendocrine control. Within the hypothalamus, orexin fibers and orexin receptors, especially OX2R, are found extensively in the paraventricular nucleus (PVN) of the hypothalamus. The PVN is an integrative center of the autonomic nervous system and the neuroendocrine system. Thus, orexins may play a role in the regulation of cardiovascular and autonomic nervous systems. This article provides a summary of our studies, in which we used direct recording of renal sympathetic nerve and PVN neuronal activities in conscious freely-moving rats and the in vitro whole cell patch-clamp technique to examine the direct effect of orexins on PVN neurons using a hypothalamic slice. Functional studies demonstrated that intracerebroventricularly (i.c.v.) administered orexins evoke increases in blood pressure, heart rate, and sympathetic nerve activity and depolarize both the magno- and parvo-cellular neurons through the activation of non-selective cation channels. The present studies suggest that PVN plays a role as one of the efferent pathways of orexin-induced activation of the sympathetic outflow.

Recent experimental studies showed the dynamic neural regulation of local bone metabolism. Increased sympathetic nervous activity has been demonstrated to cause bone loss via an increase in bone resorption and a decrease in bone formation. This review summarized both in vivo and in vitro evidences implicating sympathetic neuron action in bone resorption.

Although the cardiovascular events such as stroke, angina pectoris and myocardial infarction can occur at any time of day, it has been known that the peak incidence of the cardiovascular events increases during the morning period. In elderly hypertensives, a greater morning blood pressure surge is associated with an advanced silent cerebrovascular disease as well as a higher incidence of stroke. Thus, the blood pressure control of the early morning period may become an important therapeutic strategy for preventing the cardiovascular events. In this review, we focused on the recent strategy for morning blood pressure rising in the elderly hypertensives.

Leptin, a well-known adipokine regulating energy metabolism, inhibits bone formation via sympathetic nervous system. Recently, it was reported that adrenergic beta(2) receptor-deficient mice have high bone mass due to increased bone formation and decreased bone resorption. In addition, cocaine- and amphetamine-regulated transcript, an anorexigenic neuropeptide whose expression is regulated by leptin, has been shown to inhibit bone resorption. Thus, leptin regulates not only bone formation but bone resorption centrally.

Recent studies suggest that statins and beta-blockers which are widely prescribed for the treatment of hyperlipidemia and hypertension play an important role in bone metabolism. Statins inhibit HMG-CoA reductase and its down-stream mevalonate pathway. They modulate osteoclastic and osteoblastic activity, since metabolites of mevalonate are critically involved in bone cell biology. Sympathetic nervous system also controls bone formation via its direct effects on osteoblasts. Administration of beta-blockers may lead to an increase bone mass and reduce the risk of fracture. Statins and beta-blockers could have anabolic effects on bone metabolism and may be potential therapeutic implications for osteoporosis.

We studied sympathetic skin response (SSR) to visual emotional stimuli in 11 normal children and 13 normal adults. The arousal and valence levels of original pictures were previously assessed by 20 normal children and adults. SSR appearance ratio tended to be high for pictures with high arousal and those with either high or low valence, and was higher in children than in adults. The response for pictures with high arousal and low valence was different between children and adults. These pictures were classified into 2 groups; one consisted of disgusting creatures such as worms and roaches, and another of violent scenes, symbolizing physiological and social unpleasure, respectively. In children, SSRs were evoked with the same ratio for these two groups of pictures. In adults, however, SSRs for social unpleasure pictures were evoked with a significantly higher ratio compared to those for physiological ones. These results indicate that children are more susceptible to emotional stimuli and that this susceptibility diminishes with development, suggesting the association between emotional signal and moral development.