Clinical implications of assessing coronary flow velocity reserve and plasma endothelin-1 in hypertensive patients.

Previous reports have indicated that hypertensive patients who have angina-like chest pain and normal coronary arteriograms have reduced coronary flow velocity reserve (CFVR) levels. In addition, elevated plasma endothelin-1 (ET-1) levels have been reported to be associated with microvascular angina. The purpose of this study was to evaluate the plasma ET-1 levels and CFVR in patients with chest pain but without coronary artery disease (CAD).

Microalbuminuria and deterioration of renal function after elective repair of infrarenal abdominal aortic aneurysm.

Aims: Renal dysfunction affects the prognosis of patients after aortic surgery. However, the factors associated with the postoperative deterioration of renal function has not been clarified precisely.

Method: We prospectively examined renal function in 80 patients (age: 73 +/- 7 years, 66 males) who required the elective repair of infrarenal abdominal aortic aneurysm (AAA).

A novel missense mutation, F826Y, in the mineralocorticoid receptor gene in Japanese hypertensives: its implications for clinical phenotypes.

A gain-of-function mutation resulting in the S810L amino acid substitution in the hormone-binding domain of the mineralocorticoid receptor (MR, locus symbol NR3C2) is responsible for early-onset hypertension that is exacerbated in pregnancy. The objective of this study was to test whether other types of missense mutations in the hormone-binding domain could be implicated in hypertension in Japanese. Here, we screened 942 Japanese patients with hypertension for the S810L mutation in exon 6 in the MR.

Uric acid, left ventricular mass index, and risk of cardiovascular disease in essential hypertension.

Elevated serum uric acid (UA) is frequently encountered in individuals with hypertension, but whether the relationship between UA and cardiovascular events is circumstantial or causal remains to be answered. We examined the association between serum UA and left ventricular mass index (LVMI) and investigated prospectively whether the combination of UA and LVMI can predict the incidence of cardiovascular disease (CVD) in asymptomatic subjects with essential hypertension. A total of 619 subjects (mean age, 61 years; 52% female) free of prior CVD were included in this study.

Evaluation of intrarenal hemodynamics by Doppler ultrasonography for renoprotective effect of angiotensin receptor blockade.

Aims: It has been shown that both angiotensin-converting enzyme inhibitors (ACE-I) and angiotensin II type 1 receptor blockers (ARB) have renoprotective effects via mechanisms that are independent of blood pressure reduction. The aim of this study was to evaluate the intrarenal hemodynamic change with ARB by renal Doppler ultrasonography (RDU) and to assess the mechanism of ARB in patients with hypertension.

Methods: Thirty hypertensive patients with renal insufficiency caused by glomerular diseases, diabetes and hypertensive nephrosclerosis were included in this study.

Primary aldosteronism combined with preclinical Cushing's syndrome in an elderly patient.

Pre-clinical Cushing's syndrome (pre-CS) is sometimes seen with adrenal cortical tumors. An 80-year-old woman had severe hypertension and hypokalemia, the typical clinical features of primary aldosteronism, but detailed hormonal examinations revealed the accompanying pre-CS. After adrenalectomy by laparoscopy, her blood pressure was remarkably reduced and the hypokalemia also recovered.

Pioglitazone improves left ventricular diastolic function in patients with essential hypertension.

Background: Left ventricular (LV) hypertrophy and diastolic dysfunction, which are common cardiac consequences of hypertension, are modified by insulin resistance. The present study assessed the hypothesis that primary treatment of insulin resistance may reverse such cardiac changes in hypertensive patients.

Methods: A total of 30 patients with essential hypertension were enrolled in this study.

Genetic variations of regulator of G-protein signaling 2 in hypertensive patients and in the general population.

Objectives: Mice deficient in the regulator of G-protein signaling 2 (RGS2) exhibit a strong hypertensive phenotype. We studied whether genetic variations in RGS2 are implicated in hypertension or other phenotypes in Japanese hypertensive individuals and the general population.

Methods: We sequenced all exons of RGS2 and the promoter region in 953 and 48 hypertensive individuals, respectively.

Asymptomatic renal infarction, due to fibromuscular dysplasia, in a young woman with 11 years of follow-up.

We report a 27-year-old woman with renovascular hypertension, renal infarction, and hepatic artery aneurysm due to fibromuscular dysplasia. The patient was first noted to have renal artery aneurysm and hepatic artery aneurysm at the age of 17. The renal infarction was asymptomatic and was incidentally detected by magnetic resonance imaging (MRI) examination.

Single nucleotide polymorphisms in the interleukin-6 gene associated with blood pressure and atherosclerosis in a Japanese general population.

It is known that increased plasma levels of inflammatory markers, such as interleukin-6 (IL-6), are associated with atherosclerosis and myocardial infarction. The aim of this study was to reveal the contribution of the single nucleotide polymorphisms (SNPs) of the IL-6 gene on the blood pressure regulation and progression of atherosclerosis in a general Japanese population. In order to evaluate the potential implications of genetic variability of the IL-6 gene, we explored eight SNPs by direct sequencing for the entire coding region and the promoter region in the IL-6 gene and genotyped two SNPs, -636G > C in the promoter region and 1691C > G in intron 3, for a total of 2,421 Japanese subjects (1,162 men and 1,259 women).

[Age related hemodynamic changes in the elderly].

Systolic blood pressure (SBP) increases by aging. In contrast, diastolic blood pressure (DBP) decreases after age 60 because of lowering aortic compliance. Therefore, isolated systolic hypertension (ISH) is common in the elderly.

Left ventricular diastolic dysfunction in patients with chronic renal failure: impact of diabetes mellitus.

Aims: Left ventricular (LV) hypertrophy and LV diastolic dysfunction are cardiac changes commonly observed in patients with chronic renal failure (CRF) as well as hypertension. Although the impairment of LV diastolic function in patients with diabetes mellitus has been shown, little is known about the specific effect of diabetes on LV diastolic function in patients with CRF. The present study was designed to investigate the impact of diabetic nephropathy on LV diastolic dysfunction, independent of LV hypertrophy, in CRF patients.

Insertion/deletion polymorphism in clusterin gene influences serum lipid levels and carotid intima-media thickness in hypertensive Japanese females.

Clusterin has been implicated in lipid metabolism and atherogenesis, however, the influence of genetic variation has not been examined in Japanese. In this study, we identified 11 single nucleotide polymorphisms (SNPs) of clusterin gene by direct sequencing. Among them, one promoter SNP (-4453T>G), one missense SNP (4183G>A), and 2 common SNPs (5608T>C and 6316delT) were genotyped in 525 asymptomatic hypertensives not treated with lipid lowering agents.

Hypertension susceptibility genes on chromosome 2p24-p25 in a general Japanese population.

Background: Genome-wide scans from Italy and China suggest a hypertension-susceptible locus between D2S2278 (nucleotides 11,245,080 - 11,245,358) and D2S168 (nucleotides 11,467,214 - 11,467,422) on chromosome 2.

Methods: We performed a large association study of polymorphisms in this region with blood pressure modulation in a Japanese general population. Forty-seven polymorphisms in 14 genes between nucleotide 8,845,292 and nucleotide 11,946,689, which contains D2S2278 and D2S168, were genotyped in 1880 individuals, 796 of whom were hypertensive and 1084 normotensive.

The thiazide-sensitive Na(+)-Cl(-) cotransporter gene, C1784T, and adrenergic receptor-beta3 gene, T727C, may be gene polymorphisms susceptible to the antihypertensive effect of thiazide diuretics.

The response of blood pressure to thiazide diuretics (TZDs) differs among individuals. The prediction of the antihypertensive effect of TZDs is important for realizing individualized therapy in the management of hypertension. The aim of this study was to identify the single nucleotide polymorphisms (SNPs) susceptible to the antihypertensive effect of TZDs, particularly focusing on genes related to water-electrolyte absorption in the kidney.

Association of genetic polymorphisms of sodium-calcium exchanger 1 gene, NCX1, with hypertension in a Japanese general population.

The Na+/Ca2+ exchanger (NCX) is a membrane protein involved in calcium homeostasis, catalyzing the exchange of one Ca2+ ion for three Na+ ions across the cell membrane. The Na+/Ca2+ exchange has been suggested to play a role in the pathogenesis of hypertension. Therefore, we examined whether genetic variations in NCX1 were associated with hypertension.

Plasma asymmetric dimethylarginine and coronary and peripheral endothelial dysfunction in hypertensive patients.

Background: The attenuation of coronary flow reserve (CFR) and endothelium-mediated vasodilation of the brachial artery (EMV-BA) have been frequently reported in hypertensive patients. The present study investigated the link between CFR and EMV-BA in hypertensive patients. We hypothesized that changes in serum asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, and concomitant insulin resistance may be underlying factors connecting the two pathologic alterations.

Diagnostic and prognostic value of plasma brain natriuretic peptide in non-dialysis-dependent CRF.

Background: Brain natriuretic peptide (BNP) is useful for the evaluation of ventricular dysfunction in patients with various cardiac diseases. However, its diagnostic value has been considered to be limited in patients with chronic renal failure (CRF) because renal dysfunction itself may affect BNP levels. This study is designed to clarify the diagnostic and prognostic value of plasma BNP level in patients with CRF.

Identification of gene polymorphism in lipocalin-type prostaglandin D synthase and its association with carotid atherosclerosis in Japanese hypertensive patients.

Recent reports suggested that lipocalin-type prostaglandin D synthase (L-PGDS) is implicated in atherogenesis. In the present study, we investigated the polymorphism of the L-PGDS gene and examined its relationship with the severity of carotid atherosclerosis which is determined as the maximum intima-media thickness in the common carotid artery (C-IMT(max)). We identified 6 single nucleotide polymorphisms (SNPs) of the L-PGDS gene in Japanese.

Identification of 108 SNPs in TSC, WNK1, and WNK4 and their association with hypertension in a Japanese general population.

The deletion of thiazide-sensitive Na-Cl cotransporter ( TSC, SLC12A3) causes Gitelman's syndrome characterized by low blood pressure, while deletions of the WNK1 ( PRKWNK1) and WNK4 ( PRKWNK4) genes cause familial hypertension known as pseudohypoaldosteronism type II. Recent studies have revealed that cell surface expression of TSC is regulated by WNK1 and WNK4. We hypothesized that molecular variations in TSC, WNK1, and WNK4 could lead to an increased morbidity of hypertension.

[Hypertension].

Hypertension is one of most important components of metabolic syndrome. Main etiology of metabolic syndrome is supposed to be due to insulin resistance. Insulin resistance/hyperinsulinemia induces blood pressure elevation by sodium retention, activation of sympathetic nervous system and renin-angiotensin system(RAS) and promotion of vascular cell growth.

Evaluation of the Lys198Asn and -134delA genetic polymorphisms of the endothelin-1 gene.

Endothelin-1 (ET-1) is a potent vasoconstrictor and shows various pharmacological responses. Two single nucleotide polymorphisms in the ET-1 gene (EDN1) have been reported to be associated with blood pressure (BP). One is the Lys198Asn polymorphism, which showed a positive association with BP in overweight people.

Six missense mutations of the epithelial sodium channel beta and gamma subunits in Japanese hypertensives.

Liddle's syndrome is an autosomal dominant disease characterized by sodium-sensitive early hypertension and mutations in either the beta- or gamma-subunit of the amiloride-sensitive epithelial sodium channel encoded by SCNN1B and SCNN1G. We sequenced the 381 bp-coding regions in exon 13 of SCNN1B and the 381 bp-coding regions in exon 12 of SCNN1G in 948 and 953 Japanese patients with hypertension, respectively. In the SCNN1B gene, we identified three missense mutations, P592S (n=3), T594M (n=2), and E632K (n=1) in a heterozygous state in addition to four synonymous ones, Ile515 (n=1), Ser520 (n=19), Ser533 (n=1), and Thr594 (n=11).

Three novel missense mutations of WNK4, a kinase mutated in inherited hypertension, in Japanese hypertensives: implication of clinical phenotypes.

Background: Mutations in serine-threonine kinase WNK4 with no lysine (K) at a key catalytic residue cause familial hypertension known as pseudohypoaldosteronism type II (PHAII). The objective of this study was to test whether more subtle changes of WNK4 could be implicated in hypertension or renal failure.

Methods: We screened 956 Japanese patients with hypertension or renal failure for mutations in exons 7 and 17 in the WNK4 gene where the mutations were identified in patients with PHAII.