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(Objective) Recently, lower urinary tract symptoms (LUTS) were reported to be associated with endothelial dysfunction. Endothelial function is non-invasively measured by flow-mediated dilation (FMD). As tadalafil has the potential to improve atherosclerosis, we evaluated the relationship between LUTS and endothelial function using FMD, and the effects of tadalafil. (Patients and methods) We conducted FMD examinations for a total of 122 males, and analyzed its association with IPSS, OABSS, and cardiovascular risks. Furthermore, 21 BPH patients received 5 mg of tadalafil per day for one year. We defined the Low FMD group as FMD < 3.9% and the Control group as other values, and compared the effects of tadalafil between groups. (Results) In the 122 male patients, FMD was negatively correlated with nocturia and OABSS. Patients with hypertension or coronary artery disease had a lower FMD than those without.In the tadalafil administration study, the Low FMD group achieved greater improvement of IPSS, OABSS and FMD than the Control group. (Conclusion) FMD examination revealed that endothelial dysfunction is closely associated with LUTS in males, and that tadalafil is effective for patients with endothelial dysfunction.

The EDRF discovered in 1986 by Furchgott was later identified as NO by Ignarro. NO was a widely noted gas with diverse functions, having arginine (L-Arg) as a substrate for the NO synthase (NOS). L-Arg and L-citrulline (L-Cit) have long been associated with the urea cycle. L-Cit was produced with NO by the reaction of L-Arg and oxygen. It was shown that administration of L-Arg in animals and humans caused vasodilation and anti-arteriosclerosis effects. Despite the arginine paradox ratio of intracellular arginine concentration to the Km value of NOS gaining widespread attention, advanced arteriosclerosis is known to reduce vascular reactivity towards L-Arg. In recent years, the anti-arteriosclerosis and anti-cell aging effects of the reactive substance citrulline (L-Cit) have been studied. L-Cit and L-Arg combination therapy are starting to be considered in various clinical applications as well.

In normal condition, vasculature transports only small molecules such as nutrients across vascular wall. When inflammation occurs, inflammatory stimuli increase the permeability of vessel, which induces the extravasation of molecules larger than 40 kDa including plasma proteins. These extravasated molecules cause further inflammation by promoting the infiltration of inflammatory cells and the production of inflammatory mediators. Although it is known that vascular hyper-permeability plays an important role in inflammation, the detailed mechanism of vascular permeability regulation is still unclear. It is known that vascular permeability is controlled by two types of cells: endothelial cells and vascular mural cells. Endothelial cells cover the luminal side of vascular wall in a single layer and form endothelial barrier. Vascular mural cells regulate the blood flow volume of the downstream tissue by contracting or relaxing vascular wall. Endothelial barrier enhancement and vasocontraction suppress the vascular permeability, while endothelial barrier disruption and vasorelaxation promote it. Vascular permeability is regulated by the balance between the response of endothelial cells and vascular mural cells. Prostanoids are cell membrane-derived lipid mediators which bind to each specific G protein-coupled receptor (GPCR), prostanoid receptors. Recently, several studies showed that prostanoids regulate vascular permeability by acting on endothelial cells and/or vascular mural cells. In this review, we would like to describe the role of each prostanoid in vascular permeability by focusing on the characteristics of each specific receptor.

Metabolic syndrome is a complex of disorders that includes visceral obesity, insulin resistance, hypertension, and dyslipidemia. It is characterized by an increased risk for serious cardiovascular events. Adipocytes are now recognized to contribute to the development of cardiovascular complications in metabolic syndrome via the release of several bioactive substances (adipocytokines). Obesity induces an increase in the volume of perivascular adipose tissue (PVAT), which is located outside the blood vessels. In recent years, PVAT has been reported to produce/release vasoactive adipocytokines. Thus, PVAT can modulate vasomotor function by releasing vasorelaxing/vasocontracting factors, resulting in the development of cardiovascular disease due to metabolic syndrome. By using animal models (SHR/NDmcr-cp rats, SHRSP.Z-Lepr(fa)/IzmDmcr rats, and B6.BKS (D)-Lepr(fa)/J mice), we have demonstrated that chronic oxidative-nitrative stress is closely linked to the development of vascular dysfunction in response to nitric oxide (NO) in resistant arteries with increasing age/exposure to metabolic abnormalities. Further, our recent findings have led us to believe that PVAT helps in the regulation of vasodilation to compensate for the impaired vasodilation observed in pathophysiological conditions in the mesenteric arteries of SHRSP.Z-Lepr(fa)/IzmDmcr rats. However, a breakdown of the compensatory system occurs with long-term exposure to metabolic abnormalities. We propose the concept of the functional regulation of vascular tissue by PVAT in metabolic syndrome.

Endothelial dysfunction is thought to have pivotal roles for the development of hypertension, initiation/progression of hypertensive organ damages, and prognosis. In clinical setting, flow-mediated vasodilatation (FMD) of brachial artery is used as a marker of endothelial function. However, well-trained sonographer is needed to conduct FMD measurement, and therefore, FMD has not been fully standardized (i.e., the reference value of FMD has not been established). Even so, FMD predicts future cardiovascular events. Lifestyle modifications (i.e., smoking cessation, exercise, or weight loss) and antihypertensive medication provide beneficial effects on endothelial function. Thus, FMD have a potential as a useful surrogate marker for the management of hypertension.

Niacin, also known as vitamin B3, is required for the synthesis of coenzymes, nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP). Niacin binds with G protein-coupled receptor (GPR) 109A on cutaneous Langerhans cells and causes vasodilation with flushing in head and neck area. Niacin deficiency due to excessive alcohol consumption, certain drugs or inadequate uptake in diet causes pellagra, a photosensitivity dermatitis. Recently several studies have revealed the mechanism of photosensitivity in niacin deficiency, which may pave a way for new therapeutic approaches. The expression level of prostaglandin E synthase (PTGES) is up-regulated in the skin of both pellagra patients and niacin deficient pellagra mouse models. In addition, pellagra is mediated through prostaglandin E₂-EP4 (PGE₂-EP4) signaling via reactive oxygen species (ROS) production in keratinocytes. In this article, we have reviewed the role of niacin in immunity and the mechanism of niacin deficiency-induced photosensitivity.

The xenon light, generated by high-intensity electrical stimulation of xenon gas, is used to sterilize wounds, aid tissue repair, and relieve pain as a low-level light therapy. The light produced consists of non-coherent beams of multiple wavelengths in the ultraviolet to infrared spectrum. This broad-band light can be emitted in a continuous wave or pulsed mode, with the wave band chosen and the energy distribution controlled for the purpose. Specifically, wavelengths in the 500-700 nm range are suitable for treating superficial tissue, and wavelengths between 800 and 1,000 nm are suitable for deeper-seated tissues, due to longer optical penetration distances through tissue. One of the most common benefits in the xenon light therapy is considered to be the wide and deep irradiation of optimal rays to living tissue. Research into the use of xenon light for tissue repair and pain reduction is restricted within open-label studies and case reports. The present review expounded the effects of xenon light therapy on the basis of the available evidence in vitro and in vivo studies using a laser beam of single wavelength.

A 5-year-old girl presented with flushing and sweating on the left arm with coldness on the left palm that had persisted for approximately 24 hours. She had a fever and chicken pox-like exanthemas on her skin. She had no weakness, sensory disturbance or other autonomic dysfunction, such as orthostatic hypotension. Physical, neurological, blood and cerebrospinal fluid findings, including those of a viral study, were normal. A spinal MRI revealed no abnormal signals. Motor nerve conduction velocity, compound muscle action potential and sensory nerve conduction velocity in both medial nerves were normal, although compound sensory nerve action potential was low in the left medial nerve. F waves were absent in both medial nerves. The amplitude of the sympathetic skin response was low in the left palm. The cold-induced vasodilatation test showed bilateral sympathetic nerve dysfunction, especially on the left side. The coefficient of variation of RR intervals was low. Aciclovir was administered until chicken pox was ruled out. Subsequently, her symptoms improved. However, a sympathetic skin response and cold-induced vasodilatation findings 9 months later revealed sympathetic nerve dysfunction. These findings suggested autonomic neuropathy with local sympathetic dysfunction and a mild sensory nerve disturbance.

Angiotensin II (Ang II) signaling is mediated by two receptor subtypes, type 1 (AT(1)) and type 2 (AT(2)). The activation of AT(1) receptors is responsible for the development of Ang II-dependent hypertension, whereas the activation of AT(2) receptor is thought to play a counter-regulatory protective role in the regulation of blood pressure that opposes the AT(1) receptor-mediated vasoconstriction. However, the precise mechanisms by which increased numbers of AT(2) receptors counterbalance the AT(1)-mediated actions of Ang II are unknown. We have demonstrated that the abdominal aortic banding in mice and rats and the 2-kidney, 1-clip Goldblatt model of hypertension in mice induces up-regulation of AT(2) receptors in the pressure-overloaded thoracic aorta. In these hypertensive animals, the AT(1)-receptor antagonists but not calcium antagonist abolish up-regulation of the aortic AT(2) receptor as well as blood pressure elevation, suggesting that the pressure-overload up-regulates the aortic AT(2) receptor by Ang II via the activation of AT(1) receptor. Ang II binding to up-regulated AT(2) receptors induces vasodilation in these aortas through bradykinin B(2)-receptor-mediated phosphorylation of endothelial nitric oxide synthase (eNOS) at Ser(633) and Ser(1177) via a protein kinase A-dependent signaling pathway, resulting in sustained production of nitric oxide. These studies provide evidence that the vascular AT(2) receptor is up-regulated in the course of hypertension through the activation of AT(1) receptor, thereby activating a vasodilatory pathway in vessels through the AT(2) receptor via the bradykinin/nitric oxide/cGMP. This issue is important because the antihypertensive effect of AT(1)-receptor blockers is, at least in part, dependent on AT(2)-receptor activation.

The prevalence and natural history of cor pulmonale in COPD are not yet clear. Factors that are known to contribute to the development of pulmonary hypertension in COPD include hypoxic pulmonary vasoconstriction(HPV), remodeling of pulmonary arteries, destruction of the pulmonary capillary bed and polycythemia. In addition, impaired mechanisms of endothelium-dependent vasodilation such as reduced NO synthesis or release, and abnormal secretion of vasoconstrictor peptides play an important role in the development of pulmonary hypertension. These factors can lead to right ventricular hypertrophy and right heart failure. Pulmonary hypertension develops late in the course of COPD (stage III) usually after the development of severe hypoxemia and is associated with a poor prognosis of the disease.

It is well known that diabetes mellitus often combines with hypertension. Diabetes mellitus is associated with endothelial dysfunction. An imbalance of reduced production of nitric oxide or increased production of reactive oxygen species, mainly superoxide, may promote endothelial dysfunction. One mechanism by which endothelium-dependent vasodilation is impaired is an increase in the oxidative stress that inactivates nitric oxide. Both high glucose and insulin resistance reduce the bioavailability of nitric oxide through an increase in oxidative stress. It is unclear that endothelial dysfunction is a cause or consequence of hypertension. In this review, we present the possibility that endothelial dysfunction causes hypertension in diabetes mellitus.

There are several mechanisms about high blood pressure induced by insulin resistance in type 2 diabetes. Hyperinsulinemia is rare in Japanese type 2 diabetic patients. Therefore, hyperinsulinemia is not a major cause of high blood pressure in Japanese type 2 diabetic patients. Diabetic nephropathy was associated with high blood pressure. There was a relation between diabetic nephropathy and insulin resistance. Coexistence of essential hypertension with type 2 diabetes. Both essential hypertension and type 2 diabetes were related with insulin resistance. Vascular endothelial dysfunction was associated with insulin resistance. High blood pressure was partially caused by the endothelial dysfunction. The degree of insulin induced vasodilation was reduced in the type 2 diabetic patients with insulin resistance.

Recent advances in the properties and physiological functions of endothelium-dependent hyperpolarizing factor (EDHF) in vascular tissues were reviewed briefly. The EDHF-induced hyperpolarization is inhibited by charybdotoxin, indicating that the potential is produced mainly by activation of intermediate conductance Ca-sensitive K-channels. During generation of EDHF responses, endothelial Ca2+ concentration was elevated, suggesting that the activated K-channels were distributed on the endothelial membrane. This was confirmed by direct recording of membrane potentials from endothelial and smooth muscle cells using double patch electrodes. Measurement of the propagation of potentials applied to endothelial or smooth muscle cells to surrounding cells revealed that there were tight electrical connections between endothelial cells much more than between endothelial and smooth muscle cells or between smooth muscle cells, and these observations yielded a possible spread of electrical signal along the endothelial layer first, and then the signals would be conducted to smooth muscle cell layers. These properties of vascular tissues allow speculating that EDHF is an electrical signal propagated from endothelial cells electrotonically through myoendothelial gap junctions. Several candidates have been proposed as EDHF, and possibilities of individual substances for EDHF were discussed. The cellular mechanism of the hyperpolarization-induced vasodilatation remains unclear, and this should be clarified in the future for further understanding of the EDHF-induced vasodilatation.