Hypertension research : official journal of the Japanese Society of Hypertension
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It was reported that gene polymorphisms in the fat-mass and obesity-associated gene (FTO) were associated with obesity and diabetes in several genome-wide association studies. A recent report indicated that FTO-knockout mice exhibited phenotypes of skinny body shape and normal metabolic profiles. Thus, FTO could be important in metabolic disorders. ⋯ Although two SNPs, rs9939609 and rs1558902, were not significantly associated with hypertension, obesity, metabolic syndrome or any metabolic parameters, additive and recessive models of rs1121980 were strongly associated with plasma immunoreactive insulin (IRI) level and homeostasis model assessment insulin resistance (HOMA-IR), even after adjusting for confounding factors such as age, gender and body mass index. A haplotype of three SNPs was also significantly associated with IRI and HOMA-IR. One SNP, rs1121980, and a haplotype of three SNPs in FTO that contains this SNP, might be important in the progression of insulin resistance in Japanese subjects.
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The renin-angiotensin system (RAS) is involved in pathological mechanisms of target organ damage as well as the induction of hypertension; therefore, blockade of the RAS has been expected to prevent cardiovascular and cerebrovascular diseases beyond its antihypertensive effects. In spite of the well-characterized role of angiotensin (Ang) II receptor blockers (ARBs) in preventing the onset and recurrence of stroke, the clinical evidence for an effect of ARBs on dementia has not been definitive. However, preliminary experiments raise the possibility that treatment using ARBs may prevent ischemic brain damage and cognitive impairment. ⋯ Furthermore, recent cohort studies indicate that lower incidence of Alzheimer disease is observed in elderly individuals treated with ARBs. These results indicate a beneficial role for ARBs in cognitive impairment associated with vascular disease, Alzheimer disease, metabolic syndrome and other neurodegenerative diseases. Here, we review the effects of ARBs on the brain with a focus on dementia and future therapeutic approaches for elderly people suffering from disabilities.
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Randomized Controlled Trial Comparative Study
Rationale, design and patient baseline characteristics of OlmeSartan and calcium antagonists randomized (OSCAR) study: a study comparing the incidence of cardiovascular events between high-dose angiotensin II receptor blocker (ARB) monotherapy and combination therapy of ARB with calcium channel blocker in Japanese elderly high-risk hypertensive patients (ClinicalTrials. gov no. NCT00134160).
Higher doses of angiotensin II receptor blockers (ARBs) are expected to exert more protective effects against cardiovascular diseases. However, the significance of treatment of hypertension with high-dose ARB remains to be defined. The OlmeSartan and Calcium Antagonists Randomized (OSCAR) Study was designed to determine whether high-dose ARB monotherapy is superior to the combination therapy of ARB plus calcium channel blocker (CCB) in the prevention of cardiovascular morbidity/mortality in Japanese elderly high-risk hypertensive patients. ⋯ The primary end points will be the composite of fatal and non-fatal cardiovascular events, and death from any cause. Recruitment for the OSCAR study (around 1200 patients) was completed by the end of May 2007. The OSCAR study is the first large clinical trial comparing the efficacy of high-dose ARB monotherapy with that of an ARB plus CCB combination therapy in elderly high-risk hypertensive patients.
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Hypertensive patients with obstructive sleep apnea syndrome (OSAS) constitute a high-risk group for metabolic syndrome. OSAS directly induces negative intrathoracic pressure and decreases pulmonary stretch receptor stimulation, chemoreceptor stimulation, hypoxemia, hypercapnia and microarousal. These changes potentiate various risk factors, including the sympathetic nervous system, renin-angiotensin-aldosterone system and inflammation. ⋯ Continuous positive airway pressure (CPAP) therapy, a first-line treatment in hypertensive patients with moderate to severe OSAS, reduces ambulatory BP level, particularly during the sleep period, and midnight BP surge. However, individual differences in the BP-lowering effect of CPAP have been observed. OSAS hypertensive patients who do not tolerate CPAP remain at a high risk for cardiovascular disease because of negative intrathoracic pressure and need more aggressive antihypertensive treatment to achieve 24-h BP control with nocturnal BP <120/70 mm Hg.
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Secretory-type Na-K-2Cl cotransporter (NKCC1) is known to play roles in both acid and sodium excretion, and is more abundant in dehydration. To determine the mechanisms by which dehydration stimulates NKCC1 expression, the effects of vasopressin, oxytocin and hyperosmolality on NKCC1 mRNA and protein expressions in the outer medullary collecting duct (OMCD) of rats were investigated using RT-competitive PCR and western blot analysis. Microdissected OMCD was incubated in isotonic or hypertonic solution, or with AVP or oxytocin for 60 min at 37 degrees C. ⋯ Chronic injection of oxytocin increased the NKCC1 mRNA expression by 36%. These data showed that hyperosmolality and vasopressin stimulate NKCC1 mRNA and protein expressions in rat OMCD. It is concluded that NKCC1 expression is regulated directly and indirectly by vasopressin.