Comparison of medium-dose losartan/hydrochlorothiazide and maximal-dose angiotensin II receptor blockers in the treatment of Japanese patients with uncontrolled hypertension: the Kobe-CONNECT Study.

The objective of this study is to examine the effects of thiazide diuretics, plus medium-dose losartan versus maximal-dose angiotensin II receptor blockers (ARBs) on blood pressure (BP) in Japanese patients with uncontrolled hypertension despite the use of medium-dose ARBs. Hypertensive patients in whom BP was inadequately controlled by treatment with medium-dose ARBs alone or with calcium-channel blockers were enrolled. Patients were randomly assigned to a fixed-dose combination of 50 mg per day losartan and 12.

Role of angiotensin and the clock system in the circadian regulation of plasminogen activator inhibitor-1.

The clock system and the renin-angiotensin system (RAS) have been reported to play an important role in the circadian expression of plasminogen activator inhibitor-1 (PAI-1) gene. However, the degree of involvement of these systems remains unknown. In the present study, we investigated the roles of the clock system and the RAS in the circadian expression of PAI-1 in the peripheral tissues in vivo by using Cry1/Cry2 double knockout (Cry1/2-deficient) and angiotensin type 1 (AT1a) receptor knockout (AT1a-deficient) mice.

High salt intake elevated blood pressure but not changed circadian blood pressure rhythm in Otsuka Long-Evans Tokushima Fatty (OLETF) rat.

We examined the effect of high salt intake on mean arterial pressure and circadian blood pressure rhythm in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a model of type II diabetes mellitus. Mean arterial pressure, fasting blood glucose, and fasting plasma insulin in OLETF rats were higher than those in LETO rats, their normoglycemic controls. The amplitude of circadian blood pressure rhythm in LETO rats was smaller than that in OLETF rats.

Vascular endothelial cell-derived endothelin-1 mediates vascular inflammation and neointima formation following blood flow cessation.

Aims: Although endothelin-1 (ET-1) has been suggested to contribute to the pathogenesis of neointima formation and atherosclerosis, the individual roles of ET-1 derived from certain cell types in this disease remain unclear. In this study, we determined the role of vascular endothelial ET-1 on vascular inflammation and neointima formation using vascular endothelial ET-1-knockout [ET-1(f/f); Tie2-Cre (+)] mice.

Methods And Results: Intimal hyperplasia was induced by complete ligation of the left carotid artery in 12-week-old male ET-1(f/f);Tie2-Cre (+) mice (n = 35) and the wild-type (WT) littermates (n = 34).

Circadian expression of clock genes in human peripheral leukocytes.

In mammals, behavioral and physiological processes display 24-h rhythms that are regulated by a circadian system. In the present study, we investigated the possibility that the expression of clock genes in peripheral leukocytes can be used to assess the circadian clock system. We found that Per1 and Per2 exhibit circadian oscillations in mRNA expression in mouse peripheral leukocytes.

Circadian clock genes directly regulate expression of the Na(+)/H(+) exchanger NHE3 in the kidney.

Background: Daily rhythms in mammalian physiology are generated by a transcription/translation feedback loop orchestrated by a set of clock genes. However, little is known about the molecular cascade from the clock gene oscillators to cellular function.

Methods: The mRNA expression profiles of NHE3 and clock genes were examined in mice and rat kidneys.

Oral taurine supplementation prevents fructose-induced hypertension in rats.

Taurine is known to have antihypertensive and lipid-lowering effects in some experimental models and patients. On the other hand, intracellular free calcium and magnesium play important roles in regulating the tonus of blood vessels and insulin sensitivity. We examined the effect of oral taurine supplementation on blood pressure, serum metabolic parameters, and platelet cytosolic free calcium ([Ca(2+)](i)) and magnesium ([Mg(2+)](i)) concentration in fructose-fed Sprague-Dawley rats.

Alterations of circadian expressions of clock genes in Dahl salt-sensitive rats fed a high-salt diet.

In mammals, behavioral and physiologic processes display 24-hour rhythms that are regulated by a circadian system consisting of central and peripheral oscillators. Because various cardiovascular functions show diurnal variations and abnormal patterns of circadian blood pressure variation carry a high risk of cardiovascular complications, we investigated whether the expression of clock genes is altered in an animal model of hypertension. In Dahl salt-sensitive rats fed a high-salt (4% NaCl) diet for 6 weeks (DS-H), radiotelemetry monitoring showed increased amplitude of circadian variations in blood pressure.

Decreased ornithine decarboxylase activity in the kidneys of Dahl salt-sensitive rats.

To assess the roles of polyamines (putrescine, spermidine, and spermine) and ornithine decarboxylase (ODC), the rate-limiting enzyme of polyamine synthesis, in the development of salt-sensitive hypertension, we evaluated activity and expression of ODC, urinary polyamine excretion, and antizyme (endogenous ODC inhibitor protein) expression in Dahl salt-sensitive (SS) and salt-resistant (SR) rats after they were fed on a low (0.3%) or high (4%) salt diet for 4 weeks. We also examined the effects of spermidine and difluoromethylornithine (DFMO: a specific inhibitor of ODC) on the systolic blood pressure and ODC protein expression in SS rats fed a high salt diet.