V ascular endothelial cells play an important role in the regulation of vascular tone through the release of both vasorelaxing and vasoconstricting factors.1 Apart from the release of vasorelaxant factors such as nitric oxide and prostaglandins, endothelial cells relax the vascular smooth muscle cells through the generation of endothelium-dependent hyperpolarization (EDH). With respect to EDH, there is consensus that the activation of the small-and intermediate-conductance of Ca 2+ -activated K + channels (SK Ca and IK Ca ) located on endothelial cells results in the generation of EDH. [2][3][4][5][6][7][8] In rat mesenteric arteries, the electric transmission of EDH to the adjacent smooth muscle cells via myoendothelial gap junctions (MEGJs) plays a central role in EDH-mediated responses. [9][10][11] Several recent studies have suggested that Ca 2+ influx through endothelial transient receptor potential vanilloid 4 channel (TRPV4), a member of the TRP family of nonselective cation channels, plays a crucial role in EDHmediated hyperpolarization via the downstream activation of SK Ca and IK Ca in specific beds. 12,13 Although the mechanisms through which TRPV4 interact with SK Ca /IK Ca are not well understood, recent studies have suggested that, in specific beds, Ca 2+ influx through TRPV4 directly activates nearby IK Ca and SK Ca at the myoendothelial microdomain signaling sites to generate EDH. 12.13 In rat mesenteric arteries, it has been reported that the relative contribution of EDH in the acetylcholine-induced relaxations decreases as the vessel size increases.14 Although some previous studies reported little or no EDH-mediated relaxations in the superior mesenteric arteries of the rat, 15,16 acetylcholine evoked robust and consistent EDH-mediated Abstract-Endothelium-dependent hyperpolarization (EDH)-mediated responses are impaired in hypertension, but the underlying mechanisms have not yet been determined. (TRPV4) is a prerequisite for the activation of SK Ca /IK Ca in endothelial cells in specific beds. Here, we attempted to determine whether the impairment of EDH in hypertension is attributable to the dysfunction of TRPV4 and S/IK Ca , using isolated superior mesenteric arteries of 20-week-old strokeprone spontaneously hypertensive rats (SHRSP) and age-matched Wistar-Kyoto (WKY) rats. In the WKY arteries, EDHmediated responses were reduced by a combination of SK Ca /IK Ca blockers (apamin plus TRAM-34; 1-[(2-chlorophenyl) diphenylmethl]-1H-pyrazole) and by the blockade of TRPV4 with the selective antagonist RN-1734 or HC-067047. In the SHRSP arteries, EDH-mediated hyperpolarization and relaxation were significantly impaired when compared with WKY. GSK1016790A, a selective TRPV4 activator, evoked robust hyperpolarization and relaxation in WKY arteries. In contrast, in SHRSP arteries, the GSK1016790A-evoked hyperpolarization was small and relaxation was absent. Hyperpolarization and relaxation to cyclohexyl-[2-(3,5-dimethyl-pyrazol-1-yl)-6-methyl-pyrimidin-4-yl]-amine, a selective SK Ca activator, we...

We investigated the influence of long-term salt load on renal function in hypertensive patients. The subjects were 133 hypertensive patients (80 women and 53 men, mean age 60±9 years) who underwent at least five successful 24 h home urine collections during the 10-year observation period. Blood pressure (BP) and 24-h urinary salt and creatinine excretion levels were measured. BP decreased from 143±12/85±8 to 129±14/68±11 mm Hg during the 10.5-year observation period, and this decrease was associated with patients taking an increased number of antihypertensive drugs (1.3±1.0 to 2.2±1.1). The estimated glomerular filtration rate (eGFR) also significantly decreased from 71.7±14.6 to 64.7±16.5 ml min(-1) (P<0.01), and the change in eGFR was -0.68 ml min(-1) per year on average. The average salt excretion was 8.6±2.2 g per day and showed a significant negative correlation with the change in eGFR (r=-0.21, P=0.02). Subjects with an average salt excretion<8 g per day showed a significantly slower decline in renal function than those with an average salt excretion 8 g per day (the change in eGFR: -0.41±1.10 vs. -0.83±1.19 ml min(-1) per year, P<0.05). In the multivariate analysis, the average salt excretion (partial r=-0.19, P=0.03) and baseline eGFR (partial r=-0.23, P=0.01) were significantly associated with the change in eGFR. This association was independent of BP change or an increased number of antihypertensive drugs. The results suggest that long-term salt load promotes a decline in renal function in hypertensive patients; thus, salt restriction is encouraged, to prevent renal damage.

Objective Uric acid (UA) has shown to be a causal risk factor for the development and progression of renal disease. The aim of this study was to investigate the relationship between changes in the level of UA and trends in the renal function among hypertensive patients during a 10-year observation period. Methods The subjects included 104 hypertensive outpatients (60 women and 44 men, mean age 60±9 (SD) years at the first visit) who had undergone at least five instances of successful 24-hour home urine collection, with the first examination completed between 1998 and 2000 and the last examination completed between 2008 and 2010. Results The estimated glomerular filtration rate (eGFR) significantly decreased over the 10.4-year observation period, with an average change in eGFR of -0.66/mL/min/year. The uric acid clearance at the last examination was significantly lower than that observed at the first visit, while there were no significant differences in the serum UA levels during this period. The change in serum UA exhibited a significant negative correlation with the change in eGFR (r=-0.34, p<0.01). The patients whose UA level decreased more than 0.5 mg/ dL during the observation period demonstrated significantly smaller declines in eGFR compared to those whose UA level increased more than 0.5 mg/dL. In the multivariate analysis, the change in serum UA and the average urinary salt excretion during the observation period were found to be significantly associated with the change in eGFR, independent of age, sex, BP changes or an increased number of antihypertensive drugs. Conclusion Based on the findings observed over a 10-year observation period, increased UA is suggested to promote decline of the renal function in hypertensive patients. Controlling the level of UA as well as intensively restricting salt intake is required in order to preserve the renal function.

Since masked hypertension (MHT) is high risk for cardiovascular disease, the importance of home blood pressure (HBP) control is emphasized. The aim of this study was to investigate the prevalence of MHT in the treated hypertensives and the consequence of their BP control status after a 1-year follow up period. Subjects are 262 treated hypertensive outpatients. We assessed BP control status, background characteristics, and antihypertensive drugs in both 2008 and 2009. Clinic BP (CBP) and morning HBP in 2008 were 133 ± 12/73 ± 9 mmHg and 132 ± 11/77 ± 8 mmHg, which significantly decreased to 129 ± 11/70 ± 10 mmHg and 130 ± 10/76 ± 8 mmHg in 2009, respectively (p < 0.01). The patients with sustained hypertension (SHT) decreased from 17.9% in 2008 to 6.9% in 2009. Thirty-four percent of SHT patients in 2008 turned out to be MHT and another 34.0% belonged to normotension (NT) in 2009. Among 79 MHT patients in 2008, 62.0% remained as MHT, while 32.9% turned out to be NT in 2009. The sustained MHT patients were more male and showed a higher prevalence of habitual alcohol intake. Nighttime dosing of antihypertensive drugs and the addition of diuretics were major causes of improving morning HBP. Results suggest that one-third of MHT patients showed the improvement of HBP after the 1-year follow-up period. Not only intensive antihypertensive treatment with the appropriate use of diuretics, but also the encouragement of lifestyle modification including alcohol restriction, seems to be important to the management of MHT.

Serum uric acid levels were associated with the future incidence of hypertension, and the association was observed in the younger individuals, those without diabetes, and those with preserved high-density lipoprotein cholesterol levels in a worksite population of Japanese men.

Inflammation plays a key role in the pathogenesis of cardiovascular diseases via the development of atherosclerosis. Here, we evaluated the impact of serum C‐reactive protein (CRP) and the white blood cell (WBC) count on the risk of hypertension in middle‐aged Japanese men at a work site. We evaluated a total of 2991 Japanese male workers without hypertension who ranged in age from 18 to 64 years (mean age 40.4 ± 0.2 years) at a worksite in 2010. The hazard ratio (HR) for incident hypertension was estimated according to quartile levels of serum high‐sensitivity CRP (hs‐CRP) or WBC count. These men were followed up for 5 years from 2010 to 2015. During the follow‐up period, 579 (19.4%) subjects developed hypertension. In a multivariable analysis, the risk of incident hypertension was significantly increased with higher hs‐CRP levels: HR 1.00 (reference) for the lowest quartile, 1.39 (1.04‐1.85) for the 2nd quartile, 1.46 (1.08‐1.98) for the 3rd quartile, and 1.57 (1.17‐2.11) for the highest quartile. In contrast, the WBC count was not associated with a greater risk of incident hypertension after multivariable adjustment. These findings suggest that higher levels of serum hs‐CRP, but not the WBC count, are associated with the future incidence of hypertension in middle‐aged Japanese men.

Objective Lifestyle modification as well as combination antihypertensive therapy is necessary to achieve strict blood pressure (BP) control as advocated by the guidelines for the treatment of hypertension. The aim of this study was to investigate the status of adherence to lifestyle modifications and BP control status in hypertensive outpatients. Methods and Patients Subjects are 661 hypertensive outpatients who had been followed at National Kyushu Medical Center. We assessed BP control status based on the average clinic BP on two occasions. In addition, we investigated the adherence to the individual items of lifestyle modification by a questionnaire. Results Average BP was 129 ± 10/71 ± 11 mmHg and overall rate of achieving goal BP was 60.1%. Achieving rate of each target BP category was 83.3% in the elderly patients (<140/90 mmHg), 56.7% in the young/middle patients (<130/85 mmHg) and 45.5% in the patients with diabetes mellitus/chronic kidney disease/myocardial infarction (<130/80 mmHg). Adherance to each item of lifestyle modification was as follows: Patients who answered to be conscious about salt restriction was 80.9%, those with increased intake of fruits/vegetables was 79.0%, reduced intake of cholesterol/saturated fatty acids was 67.9%, presence of obesity was 37.7%, daily exercise for !30 min was 31.9%, habitual alcohol intake was 38.0%, habitual smoking was 9.8%. Only 22.5% of the patients had no lifestyle items to be modified. On the other hand, 19.6% of patients had more than 3 items to be modified. Subjects with more than 3 lifestyle items to be modified are more frequently found in young, male, and obese groups. Conclusion We conclude that about 60% of the patients achieved goal BP by the intensive combination therapy. The lifestyle modification seems to be important especially for the young, male and obese patients.

Objective:We report a case of stent fracture caused by an elongated styloid process, a form of Eagle syndrome.Case Presentation: A 58-year-old man presented with sudden right hemisensation disturbance and aphasia. MRI revealed multiple acute cerebral infarction in the left parietal and insula cortex. MRA revealed a left-sided internal carotid artery (ICA) occlusion distal to the carotid bifurcation. Digital subtraction angiography (DSA) revealed a left-sided ICA dissection distal to the carotid bifurcation. We performed acute revascularization with aspiration of the thrombus and stenting to treat the carotid dissection. Recanalization with thrombolysis in cerebral infarction (TICI) grade III was achieved. We performed DSA 3 months after an operation, it showed stent fracture and aneurysmal formation in the stent fractured department. From CT findings, the carotid artery dissection and stent fracture appeared to be triggered by the elongated styloid process. We performed stent-assisted coil embolization. After conducting percutaneous transluminal angioplasty (PTA) at high pressure after coil embolization, the elongated styloid process was fractured, and accepted a shift to the outside of the stent contact department. The patient was discharged without medical problems, and no recurrence was observed for 2 months after the surgery. Conclusion:We experienced a rare case of ICA dissection and carotid stent fracture from Eagle syndrome. Eagle syndrome is an important disease to consider in the differential diagnosis of extracranial carotid artery dissection.