Hypertension research : official journal of the Japanese Society of Hypertension
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Preeclampsia is a multifactorial disorder with genetic and environmental components. As Toll-like receptor 4 (TLR4) has an essential role in innate immune response, which is exaggeratedly activated in preeclampsia, our aim was to investigate whether two single nucleotide polymorphisms (SNPs) of the TLR4 gene--Asp299Gly (A896G) and Thr399Ile (C1196T)--are associated with preeclampsia in a Caucasian population from Hungary. In a case-control study, we analyzed blood samples from 180 preeclamptic patients and 172 normotensive, healthy pregnant women with the polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) method. ⋯ In conclusion, we did not find an association between TLR4 Asp299Gly and Thr399Ile gene polymorphisms and preeclampsia. As the Thr399Ile polymorphism is a highly informative tag SNP of the TLR4 gene, our results suggest that variations in this genomic region are not associated with preeclampsia. Nevertheless, further studies are required with determination of fetal TLR4 genotypes to explore the role of TLR4 gene polymorphisms in the risk of preeclampsia, especially in ethnically different populations.
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Recent clinical studies have demonstrated that transient postprandial hyperglycemia and hyperinsulinemia may contribute to the development of hypertension. Therefore, we investigated the influence of acute hyperglycemia and/or hyperinsulinemia induced by glucose or insulin infusion on neuronal and humoral control of vascular tone in rats. Euglycemic male Wistar rats were pithed under anesthesia and arterial blood pressure was measured. ⋯ In pithed rats treated with octreotide, which increased blood glucose without increasing serum insulin levels, glucose infusion caused only significant augmentation of adrenergic nerve-mediated pressor responses. Combined infusion of insulin and glucose, which resulted in increased serum insulin levels with euglycemia, significantly augmented adrenergic nerve-mediated pressor responses and attenuated CGRPergic nerve-mediated depressor responses. The present results suggest that acute hyperglycemia and hyperinsulinemia increase adrenergic nerve-mediated vasoconstriction, which in turn blunts CGRPergic nerve function, and that the increase in plasma insulin concentration associated with hyperglycemia may be responsible for the alteration of neuronal vascular regulation.
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This study investigated the effects of rosiglitazone on nutritionally programmed chronic disease, with a focus on blood pressure (BP) and aortic wall structural remodeling. Wistar pregnant rats were fed one of two diets: a normal protein diet (19% protein; NP rats) or low-protein diet (5% protein; LP rats). Male offspring at 3 months of age were randomly divided into four groups: NP offspring treated with rosiglitazone (NPR); untreated NP offspring (NP); LP offspring treated with rosiglitazone (LPR); untreated LP offspring (LP). ⋯ Rosiglitazone restored the expressions of angiotensin II type 1 receptor and endothelial nitric oxide synthase nearly to the levels in the NP offspring. ANOVA disclosed a significant two-factor interaction between protein content in the diet and rosiglitazone treatment (p < 0.001 for CWT and p < 0.00001 for TS, two-way ANOVA). We conclude that rosiglitazone has beneficial effects in reducing the BP and the aortic tunica media hypertrophy with consequent balance of the wall stress in metabolically programmed offspring.
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Randomized Controlled Trial Multicenter Study
Effect of renin-angiotensin-aldosterone system triple blockade on non-diabetic renal disease: addition of an aldosterone blocker, spironolactone, to combination treatment with an angiotensin-converting enzyme inhibitor and angiotensin II receptor blocker.
Although dual blockade of the renin-angiotensin-aldosterone system (RAAS) with the combination of an angiotensin-converting enzyme inhibitor (ACE-I) and angiotensin II receptor blocker (ARB) is generally well-established as a treatment for nephropathy, this treatment is not fully effective in some patients. Based on the recent evidence implicating aldosterone in renal disease progression, this study was conducted to examine the efficacy of blockade with three different mechanisms by adding an aldosterone blocker in patients who do not respond adequately to the dual blockade. A 1-year randomized, open-label, multicenter, prospective controlled study was conducted, in which 32 non-diabetic nephropathy patients with proteinuria exceeding 0.5 g/day were enrolled after more than 12 weeks of ACE-I (5 mg enalapril) and ARB (50 mg losartan) combination treatment. ⋯ The decreases in urinary protein and urinary type IV collagen were not accompanied by a decrease in blood pressure. Mean serum creatinine, potassium and blood pressure did not change significantly by either treatment. In conclusion, triple blockade of the RAAS was effective for the treatment of proteinuria in patients with non-diabetic nephropathy whose increased urinary protein had not responded sufficiently to a dual blockade.