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Background The relationship between tumor necrosis factor (TNF)-related parameters and cardiorenal metabolic factors is still controversial in clinical hypertension.Methods Normotensive men (NT, n=60) and treated stage 2 and 3 essential hypertensive men (HT, n=89) were enrolled in this study. The relationship between TNF-related parameters and cardiorenal metabolic factors was examined in NT and HT, separately.Results HT showed higher rates of insulin resistance and enhanced chronic inflammation compared with NT. The levels of soluble TNF receptor 1 and 2 were significantly higher in HT than in NT, although TNF-α levels were unexpectedly lower in HT than in NT. Regression analysis indicated that the TNF-related parameters were closely linked with mild renal dysfunction both in NT and HT, and moderately related to chronic inflammation only in HT. HT taking inhibitors of the renin-angiotensin system showed improved insulin resistance, but no difference in the TNF-related parameters.Conclusion These results suggest that the disturbed TNF system is closely linked with chronic inflammation rather than with insulin resistance in HT.

Calcium channel blockers are the strongest and most widely used antihypertensive drugs in Japan. Calcium channel blockers dilate both artery and arteriole that increases end-organ perfusion, thus possessing few side effects especially for the elderly hypertensive patients. The safety of calcium channel blockers was well established. In this paper, important clinical evidence supporting the effectiveness of calcium channel blockers and improving cardiovascular endpoints will be reviewed. Calcium channel blockers protect end-organs from hypertensive vascular injury. In addition, calcium channel blockers show non-inferiority to angiotensin converting enzyme inhibitors, angiotensin receptor blockers and diuretics regarding cardiovascular endpoints. Furthermore, calcium channel blockers may have superiority to betablockers. Although cardiovascular protection by calcium channel blockers largely depends on their potent blood pressure lowering ability, including central blood pressure, calcium channel blockers can manifest blood pressure-independent vascular protection. Thus, calcium channel blockers are basic antihypertensive drugs, and constitute the treatment of choice to obtain target blood pressure for most hypertensive patients, especially for high-risk population and those with resistant hypertension. An intense treatment of hypertension with adequate doses of calcium channel blockers is mandatory to improve cardiovascular prognosis.

Macrophages uptake oxidized low-density lipoprotein (LDL) via a scavenger receptor such as CD36 from plasma, and then become foam cells. We examined the association of CD36 gene single nucleotide polymorphisms (SNPs) with certain metabolic characteristics in a young male Japanese population (n  494). The G allele in a SNP located at 30215 on the 3’-untranslated region (UTR) was significantly correlated with the plasma LDL-cholesterol concentrations (r  0.13, p <0.01). The difference in LDL-cholesterol concentrations was 10 mg dl−1between GG- and AA-genotype carriers (p <0.05). The CD36 gene SNP is a novel maker of the variation in the LDL-cholesterol levels in young Japanese men.

Increased Na-Hexchanger activity (NHE) has been reported as an intermediate phenotype in hypertensive subjects, particularly those with insulin resistance. To investigate whether NHE abnormality plays a role in hypertension, Wistar fatty rat (WFR) with overt obesity, hyperglycemia and marked hyperinsulinemia was examined.

To investigate the effects of oestrogen supplementation after ovariectomy on systolic blood pressure and platelet aggregation on different sodium content diet in the female Dahl salt-sensitive rats.

A cosegregation analysis of sarco(endo)plasmic reticulum Ca2+-dependent ATPase (SERCA) II genotype, systolic blood pressure and platelet intracellular Ca2+concentration was performed to dissect polygenic hypertensive traits in spontaneously hypertensive rats. Backcross analysis between spontaneuosly hypertensive rats and normotensive Donryu rats demonstrated the existence of an inferred single major gene locus (ht). Thrombin-stimulated intraplatelet Ca2+concentration was significantly higher in the SERCA II homozygotes than in the heterozygotes. The SERCA II genotype did not cosegregate with the blood pressure level. The SERCA II gene was assigned to rat chromosome 12. These results suggest that the SERCA II gene on rat chromosome 12 contributes to increased thrombin-stimulated intraplatelet Ca2+concentration and that the SERCA II gene is not identical toht.

The sensitivity for the chemiluminescent (CL) detection of nucleosides and their derivatives was improved by using clinoptirolite chemically modified with cupric nitrate, Cu-Zeo. Cu-Zeo plays a key role as a solid medium for such so-called material exchangers as ion exchange between copper(II) coated on Cu-Zeo and nucleosides and their derivatives. The properties for material exchange were examined by a batch method in which Cu-Zeo (1.5 g; particle size, 250 mesh) was added into the analyte solution (100 ml). Analytes were indirectly determined by the CL analysis of cupric ions eluted from the Cu-Zeo through the material exchange. For the CL detection of cupric ions, an FIA/CL system using a 1,10-phenanthroline CL was employed. The lower limits of detection for analytes were improved by 42 times for adenosine (1.9 pmol/20 μl) and by 16 times for uridine-5’-diphosphate (5.5 pmol/ 20 μl), compared with those by our previous method.

Chemiluminescence (CL) observed in a reaction between OH radicals and nucleosides or their derivatives is applied to their sensitive determinations by a flow injection method. The OH radicals are produced by the reaction with hydrogen peroxide and cobalt(II)-l,10-phenanthroline complex in alkaline solution. The proposed flow system is comprised of three flow lines for cobalt(II), 1,10-phenanthroline and hydrogen peroxide. The proposed CL is specific to nucleosides and their related compounds. Their detection limits ranged from 68 pmol (uridine-5′-diphosphoglucose; UDP-Glu) to 89 pmol (guanosine) in a 10 ul injection volume. The relative standard deviation is 1.2 % in 5 repeated runs for UDP-Glu of 178 pmol in a 10 μl injection volume. Analytical time required is ca. 2 s.

To determine whether insulin sensitivity is impaired in normotensive offspring of essential hypertensives and to investigate how it relates to disturbed calcium metabolism

A new chemiluminescence reaction system using hydrogen peroxide/ sodium hydroxide/brilliant sulfoflavine was successfully applied to a flow-injection analysis (F1A) for the specific determination of adenosine-5’-triphosphate (ATP). The analytical system comprised two flow lines (Li and L2) with a 20 μl injector; 5% hydrogen peroxide and 5.0×10-3M (mol/1) sodium hydroxide/ 1.0×10-3M brilliant sulfoflavine were passed through the L1and L2at a flow rate of 4.5 ml/ min, respectively. The analytical properties of ATP were as follows: the lower detection limit was 1.0×10-5M (S/N=2); the determination range, 1.0×10-3-5.0×10-3M; the analytical time required, 8 s; the reproducibility, 2.1% in terms of the relative standard deviation in 5 repeated runs for 5×10-3M ATP. Regarding the selectivity, the CL intensity for 1.0×10-3M ATP was not interfered with by other nucleotides coexisting at 100-times higher concentration than ATP. A recovery test of ATP in a human urine matrix was also performed.

Recombinant human soluble thrombomodulin (rhsTM) is newly developed for the treatment of DIC. The purpose of this study was to evaluate the efficacy of the concomitant administration of rhsTM and antithrombin (AT).

To search for a genetic marker of the sarco-(endo)plasmic reticulum Ca2-dependent ATPase (SERCA) II gene in spontaneously hypertensive rats (SHRs) and to investigate differences in blood pressure and intracellular Ca2among some substrains of SHRs and Wistar–Kyoto (WKY) rats related to their SERCA II genotypes.

Our purpose was to determine the effect of ovariectomy on intracellular Ca2+ mobilization and platelet aggregation in sodium induced hypertension. At the age of 12 weeks ovariectomy or sham operation was performed in female Dahl-Iwai salt sensitive rats on a 0.3% NaCl diet. Four weeks later we assessed the effects of ovariectomy and an 8% NaCl diet on agonist induced intracellular Ca2+ mobilization in fura-2 loaded platelets and platelet aggregation. Ovariectomy enhanced the increase of systolic blood pressure and heart to body weight ratio on an 8% NaCl diet. However, thrombin evoked intracellular Ca2+ was not correlated with systolic blood pressure (r = -0.338, P = .17), and was lowered by sodium loading and ovariectomy (360 ± 23 to 285 ± 9, 296 ± 10 nmol/L, P < .05). Furthermore, the ionomycin induced intracellular calcium fraction in the absence of external Ca2+ that reflected internal Ca2+ discharge capacity was reduced in ovariectomized rats compared with sham operated rats on an 8% NaCl diet (648 ± 15 v 768 ± 35 nmol/L, P < .05). The internal Ca2+ discharge capacity was inversely correlated with systolic blood pressure (r = -0.506, P = .03). In addition to the decreased internal Ca2+ discharge capacity, intracellular Ca2+-independent platelet aggregation by phorbol 12-myristate 13-acetate, a protein kinase C activator, was significantly enhanced in hypertensive rats. We concluded that ovariectomy enhanced sodium induced hypertension associated with the decreased internal Ca2+ discharge capacity and increased platelet aggregation in Dahl-Iwai salt-sensitive rats. Am J Hypertens 1997;10:1326–1334 © 1997 American Journal of Hypertension, Ltd.

Hypertension is characterized by a complex mode of inheritance, consisting of the accumulation and interaction of major and minor genes. The existence of a single major gene locus (ht) has been demonstrated in the backcross analysis of spontaneously hypertensive rats (SHR) and normotensive Donryu rats. Intracellular Ca2+ concentration ([Ca2+]i) determines the tonus of vascular smooth muscle. It has been hypothesized that abnormal Ca2+ transport is an inheritable trait with profound influence on the development of hypertension. Backcross analysis between SHR and Donryu rats was performed to demonstrate ht and to dissect polygenic hypertensive traits through ht and abnormal intracellular Ca2+ metabolism. Among the parental strains, systolic blood pressure and thrombin-stimulated [Ca2+]i in platelets were significantly greater in SHR than in Donryu and F1 rats. The backcrossed rats were distributed into two clusters on a scattergram of blood pressure versus [Ca2+]i, demonstrating the existence of ht. The blood pressure level was correlated with thrombin-stimulated [Ca2+]i in each cluster. Increased [Ca2+]i in platelets was not coinherited with ht and was considered to be a minor inheritable hypertensive trait discriminated from ht. Therefore, [Ca2+]i in platelets is an inadequate marker for searching ht. © 1997 American Journal of Hypertension, Ltd. Am J Hypertens 1997;10:282–288