Yoshio Uehara

Caffeine and cardiovascular diseases: critical review of current research

AbstractnCaffeine is a most widely consumed physiological stimulant worldwide, which is consumed via natural sources, such as coffee and tea, and now marketed sources such as energy drinks and other dietary supplements. This wide use has led to concerns regarding the safety of caffeine and its proposed beneficial role in alertness, performance and energy expenditure and side effects in the cardiovascular system. The question remains “Which dose is safe?”, as the population does not appear to adhere to the strict guidelines listed on caffeine consumption. Studies in humans and animal models yield controversial results, which can be explained by population, type and dose of caffeine and low statistical power. This review will focus on comprehensive and critical review of the current literature and provide an avenue for further study.n

Japanese traditional miso soup attenuates salt-induced hypertension and its organ damage in Dahl salt-sensitive rats

OBJECTIVEnWe investigated the effects of long-term miso soup drinking on salt-induced hypertension in Dahl salt-sensitive (Dahl S) rats.nnnMETHODSnDahl S rats were divided into four groups that consumed 1) water, 2) a 0.9% NaCl solution, 3) a 1.3% sodium NaCl solution, or 4) miso soup containing 1.3% NaCl. They were followed for 8 wk. Systolic blood pressure and hypertensive organ damage were determined.nnnRESULTSnSystolic blood pressure increased in an age- and dose-dependent manner in Dahl S rats drinking salt solutions. The systolic blood pressure increase was significantly less in the Dahl S rats that drank miso soup, although the ultimate cumulative salt loading was greater than that in the Dahl S rats given the 1.3% NaCl solution. This blood pressure decrease was associated with a morphologic attenuation of glomerular sclerosis in the kidney and collagen infiltration in the heart. Urinary protein excretions were less in the miso group than in the rats given the 1.3% NaCl solution. The fractional excretion of sodium was increased and that of potassium was decreased in Dahl S rats given the 1.3% NaCl solution, and these effects were reversed in rats given miso soup toward the values of the control.nnnCONCLUSIONnWe found that long-term miso soup drinking attenuates the blood pressure increase in salt-induced hypertension with organ damage. This may be caused by a possible retardation of sodium absorption in the gastrointestinal tract or by the direct effects of nutrients in the miso soup from soybeans. The decrease was associated with decreases in cardiovascular and renal damage.

Sodium Alginate Oligosaccharides Attenuate Hypertension and Associated Kidney Damage in Dahl Salt-Sensitive Rats Fed a High-Salt Diet

Objectives: In this article, the antihypertensive effects of sodium alginate oligosaccharides, enzymatic products of high molecular natural alginate from sea weeds, in Dahl salt-sensitive (Dahl S) rats were investigated. Material and Methods: Dahl S rats fed a high-salt (4% NaCl) diet were treated with sodium alginate oligosaccharides (4% or 8% w/w) for 7 weeks. Systolic blood pressure (SBP) was measured by the tail-cuff method, and hypertensive cardiovascular benefits and kidney damage were assessed. Glomerular function and morphological sclerosis were determined. Results: SBP increased in an age-dependent manner in the untreated Dahl S rats. Sodium alginate oligosaccharide treatment attenuated the increase in SBP in a dose-dependent manner. The heart and aortic walls weighed less in the rats treated with sodium alginate oligosaccharides than in the untreated rats. The SBP reduction was associated with a decrease in urinary protein excretion and an increase in the creatinine clearance rate. Sodium alginate oligosaccharides significantly attenuated hypertensive glomerular sclerosis and arterial injury in the kidney. Fractional excretion of sodium (FENa) decreased in low-salt Dahl S rats and increased with a salt challenge. The alginate oligosaccharides decreased FENa in high-salt Dahl S rats. Conclusions: The results of this study suggest that sodium alginate oligosaccharides attenuate salt-induced hypertension in Dahl S rats. This reduction is associated with decreases in cardiovascular and renal damage.

Orthostatic hypotension in diabetic patients—10-year follow-up study

INTRODUCTIONnCardiovascular autonomic neuropathy in diabetics is a common but often underestimated and underdiagnosed complication of diabetes mellitus. One of the most clinical apparent forms of cardiovascular autonomic neuropathy is orthostatic hypotension.nnnOBJECTIVESnTo retrospectively assess the association of the orthostatic hypotension (OH) with macrovascular and microvascular complications of diabetes mellitus and to determine its effect on mortality.nnnDESIGN AND METHODSnWe retrospectively analyzed 187 patients with diabetes mellitus (60 patients with diabetes type 1 and 127 patients with diabetes type 2). Patients were divided into groups according to presence or absence of OH and type of diabetes. Association of OH with macrovascular and microvascular complications was evaluated and the effect of OH on 10-year all-cause mortality was also assessed.nnnRESULTSnOH was present in 31.7% of patients with diabetes type 1 (DM1) and in 32.3% of patients with diabetes type 2 (DM2). OH was positively associated with the prevalence of myocardial infarction in DM1 (OR=10.67) and with prevalence of stroke in DM2 (OR=3.33). There was also a strong association of OH and the prevalence of peripheral artery disease in both DM1 (OR=14.18) and DM2 (OR=3.26). Patients with both types of diabetes and OH had significantly higher prevalence of nephropathy (DM1 OR=8.68, DM2 OR=3.24), retinopathy (DM1 OR=8.09, DM2 OR=4.08) and peripheral neuropathy (DM1 OR=17.14, DM2 OR=7.51) Overall 10year mortality rate was higher in diabetic patients with OH.nnnCONCLUSIONSnPresence of OH in diabetics is associated with higher prevalence of macrovascular and microvascular complications of diabetes mellitus and also with higher 10-year mortality.

Subcutaneous Administration of Sodium Alginate Oligosaccharides Prevents Salt-Induced Hypertension in Dahl Salt-Sensitive Rats

Objective: We investigated the mechanism of antihypertensive effects of sodium alginate oligosaccharides, which are enzymatic products of high-molecular-weight natural alginate from seaweeds, in Dahl salt-sensitive (Dahl S) rats. Materials and Methods: Dahl S rats fed a high-salt (4% NaCl) diet were subcutaneously administered sodium alginate oligosaccharides (60 mg/day using a continuous osmotic mini-pump) for 14 days. Systolic blood pressure (SBP) was measured using the tail-cuff method, and we determined the influence of the alginate treatment on the metabolism of sodium by measuring sodium excretions in the feces and urine. Results: SBP increased in an age-dependent manner in the untreated Dahl S rats. Sodium alginate oligosaccharide treatment via the subcutaneous route almost completely abolished salt-induced hypertension in Dahl S rats fed a high-salt diet. The level of fecal or urinary sodium excretion did not significantly change during the treatment period with the alginate oligosaccharides. The reduction in SBP rapidly recovered after cessation of the treatment. Moreover, the level of urinary protein excretion was lower in the treated Dahl S rats than in the untreated rats during the experimental period. Conclusions: Our results suggest that sodium alginate oligosaccharides attenuate salt-induced hypertension in Dahl S rats not through reducing salt absorption, but probably through a direct action on vascular vessels.

Sodium Alginate Oligosaccharides Attenuate Hypertension in Spontaneously Hypertensive Rats Fed a Low-Salt Diet

We investigated the effects of sodium alginate oligosaccharides (alginate) on the development of spontaneous hypertension in rats. Spontaneous hypertensive rats were treated with alginate for 7 weeks. Systolic blood pressure (SBP) and cardiovascular and kidney damage were assessed. Systolic blood pressure increased in SHRs and this elevation was attenuated with alginate treatment. The heart weight tended to decline. Alginate did not change plasma cholesterol levels or urinary sodium excretions. The slightly higher urinary protein excretion in SHRs was not changed with the treatment; however, morphologic glomerular damage was significantly attenuated. Sodium alginate oligosaccharide attenuates spontaneous hypertension in SHRs, and may help prevent early-stage kidney injury.

Breastfeeding and prevalence of allergic diseases in Japanese university students

BACKGROUNDnAlthough historical support exists for the concept that breastfeeding might be protective against allergic diseases, contradictory findings have been observed recently.nnnOBJECTIVEnTo investigate the cumulative prevalence of allergic diseases in Japanese university students and to identify explanatory variables including breastfeeding.nnnMETHODSnFrom March 18, 2003, through March 29, 2005, a total of 9,615 students newly enrolled at the University of Tokyo responded to a written questionnaire on allergic diseases.nnnRESULTSnCumulative prevalence of allergic rhinitis, atopic dermatitis, and asthma was 47.2%, 17.4%, and 9.3%, respectively. These data were closely correlated, and prevalence of any 1 of the 3 diseases significantly increased the odds for historical prevalence of the other 2 (P < .001). Male sex (odds ratio [OR], 1.5; 95% confidence interval [CI], 1.4-1.7) and maternal (OR, 2.2; 95% CI, 2.0-2.5) or paternal (OR, 1.6; 95% CI, 1.4-1.8) history of allergic rhinitis were significant correlates of increased odds for allergic rhinitis. Maternal (OR, 2.7; 95% CI, 1.6-4.5), paternal (OR, 3.8; 95% CI, 2.2-6.6), or sibling (OR, 1.9; 95% CI, 1.5-2.4) history of atopic dermatitis was a significant correlate of increased odds for atopic dermatitis. As for asthma, maternal (OR, 4.9; 95% CI, 3.0-7.9), paternal (OR, 4.0; 95% CI, 2.3-7.0), or sibling (OR, 3.3; 95% CI, 2.4-4.5) history of asthma was a significant correlate of increased odds. Logistic regression analysis showed no consistent evidence of the effects of breastfeeding on the cumulative prevalence.nnnCONCLUSIONnThe cumulative prevalence of these diseases among young adults revealed that the effect of breastfeeding is negligible when compared with genetic factors.

Angiotensinogen gene polymorphisms and food-intake behavior in young, normal female subjects in Japan

OBJECTIVEnWe examined whether angiotensinogen (AGT) gene polymorphisms are associated with food preferences in young, normal female subjects.nnnMETHODSnFifty-two young, normal female subjects (21-22 y old) were recruited. After a 12-h fast, blood samples were obtained to examine the AGT gene polymorphisms (rs699 and rs7079), angiotensin-converting enzyme (ACE) insertion (I)/deletion (D), and adrenergic β3 receptor (ADRB3) gene polymorphisms (rs4994). A trained dietitian interviewed the participants to determine the portion size and frequency of food eaten for 1 wk by using the established questionnaire FFQg 3.0.nnnRESULTSnThe genotypes of the AGT Met235Thr polymorphisms were TT:TC:CC = 2:19:31 (T:C = 0.22:0.78). The genotypes of AGT rs7079 were CC:CA:AA = 26:21:5 (C:A = 0.70:0.30), and those of ACE were DD:DI:II = 5:28:19 (D/I = 0.37:0.63). The genotypes of ADRB3 Trp64Arg were TT:TC:CC = 38:11:3 (T:C = 0.84:0.16). The total caloric intake was greater for those with the MM/MT genotype of AGT Met235Thr than for those with the TT genotype (1993 versus 1698 kcal/d, P < 0.05). The consumption of total lipids, cholesterol, and unsaturated free fatty acids was also higher in those with the MM/MT genotype of AGT Met235Thr than in those with the TT genotype. However, the AGT polymorphism (rs7079) and the ACE I/D were not associated with food preferences. In contrast, the subjects with ADRB3 Trp64 tended to show a high energy intake and preferences for proteins and lipids including fatty acids and cholesterol. They ate more fish and meat. Multiple regression analysis showed that the energy intake in subjects with the MM/MT genotype was independently determined by total lipids (B = 11.7, P < 0.0001) and carbohydrates (B = 4.6, P < 0.0001).nnnCONCLUSIONSnThe AGT Met235Thr polymorphism was significantly associated with a higher caloric intake owing to total fat and carbohydrate consumption.

TRPV currents and their role in the nociception and neuroplasticity

Transient receptor potential channels sensitive to vanilloids (TRPVs) are group of ion channels which are sensitive to various tissue damaging signals and their activation is generally perceived as pain. Therefore, they are generally named as nociceptors. Understanding their activation and function as well as their interaction with intracellular pathways is crucial for the development of pharmacological interference in order to reduce pain perception. The current review summarizes basic facts in regard to TRPV and discusses their relevance in the sensing of (pain-) signals and their intracellular processing, focussing on their modulation of the intracellular calcium ([Ca(2+)]i) signal. Furthermore we discuss the basic mechanisms how the modification of [Ca(2+)]i through TRPV might induce long-term-potentiation (LTP) or long-term- depression (LTD) and from memories of pain. Understanding of these mechanisms is needed to localize the best point of interference for pharmacological treatment. Therefore, high attention is given to highlight physiological and pathological processes and their interaction with significant modulators and their roles in neuroplasticity and pain modulation.

Blood pressure reduction by Japanese traditional Miso is associated with increased diuresis and natriuresis through dopamine system in Dahl salt-sensitive rats

Abstract Objectives: We investigated the antihypertensive mechanism of long-term Miso soup consumption in Dahl salt-sensitive (Dahl S) rats with salt-induced hypertension. Material and Methods: Female Dahl S rats fed a low-salt (0.3% NaCl) diet were divided into three groups: (1) six rats given water, (2) six rats given 0.65% (w/v) saline solution or (3) eight rats given 5% (w/v) Miso soup containing 0.65% (w/v) saline solution. They were followed for 12 weeks. Variables in the plasma or 24-h urine were determined. Systolic blood pressure (SBP) was measured by the tail-cuff method. Results: The SBP increased in an age-dependent manner in Dahl S rats drinking saline solutions. The elevation of SBP was significantly attenuated in Dahl S rats given Miso soup although the ultimate cumulative salt loading was much greater in the Miso group than those given the saline solutions. This SBP reduction in the Miso group was associated with an increase in fractional excretion of Na (FENa) and free water clearance in the kidney. Urinary dopamine excretions were increased in the Miso group compared with that in the saline group. The increase in urinary dopamine excretions was associated with a decrease in brain oxidative stress. Urinary dopamine excretions were an independent predictor of SBP in the Miso group. Conclusions: Long-term consumption of Miso soup attenuated blood pressure elevation in Dahl salt-sensitive rats with salt-induced hypertension. The blood pressure reduction was due to, at least in part, constituent(s) of the Miso that increase natriuresis and diuresis and enhance dopaminergic nervous activity in the kidney.