PubMed Health⌕ Search

Biomedical subjects

Ryoji Ozono

Publications and source records attributed to Ryoji Ozono.

At least 19 recordsLinked to original sources
PubMed2006

AT2 receptor mediates the cardioprotective effects of AT1 receptor antagonist in post-myocardial infarction remodeling.

There are two subtypes of angiotensin (Ang) II receptors, AT1R and AT2R. It is established that clinical use of specific AT1R blocker (ARB) improves the long-term prognosis of heart failure. However, scientific basis for such effects of ARB is incompletely understood. The present study was designed to determine whether ARB inhibits the left ventricular (LV) remodeling that occurs early after myocardial infarction (MI) and whether the benefit of ARB is mediated by blockade of AT1R itself or by stimulation of AT2R resulting from AT1R blockade. MI was induced in AT2R-knockout mice and wild-type mice. Administration of valsartan, an ARB, or vehicle was started soon after the surgery and continued for two weeks. Infarction caused significant increase in end diastolic and end systolic LV dimensions, LV/body weight ratio, and myocyte cross-sectional area (MCSA) in both strains to a similar extent. Lung/body weight ratio, an index of pulmonary congestion, was also significantly increased in both strains, but the magnitude of increase was significantly larger in knockout mice. Valsartan significantly reduced LV dimensions, LV/body weight ratio, MCSA, and lung/body weight ratio in wild-type mice. In knockout mice, however, valsartan failed to inhibit the increases in LV dimensions and LV/body weight ratio. After the treatment, lung/body weight ratio in the mutant strain was significantly larger than that in the wild-type mice. Valsartan attenuates acute phase post-infarction remodeling and ameliorates heart failure, and a large part of its cardioprotective effect was mediated by AT2R.

Angiotensin II Type 1 Receptor Blockers↗
PubMed2006

Genetic ablation of the transcription repressor Bach1 leads to myocardial protection against ischemia/reperfusion in mice.

Bach1 is a transcriptional repressor of heme oxygenase-1 gene (Hmox-1) and beta-globin gene. Heme oxygenase (HO)-1 is an inducible cytoprotective enzyme that degrades pro-oxidant heme to carbon monoxide (CO) and biliverdin/bilirubin, which are thought to mediate anti-inflammatory and anti-oxidant actions of HO-1. In the present study, we investigated the role of Bach1 in tissue protection against myocardial ischemia/reperfusion (I/R) injury in vivo using mice lacking the Bach1 gene (Bach1(-/-)) and wild-type (Bach1(+/+)) mice. In Bach1(-/-) mice, myocardial expression of HO-1 protein was constitutively up-regulated by 3.4-fold compared to that in Bach1(+/+) mice. While myocardial I/R induced HO-1 protein in ischemic myocytes in both strains of mice, the extent of induction was significantly greater in Bach1(-/-) mice than in Bach1(+/+) mice. Myocardial infarction was markedly reduced in size by 48.4% in Bach1(-/-) mice. Pretreatment of Bach1(-/-) mice with zinc-protoporphyrin, an inhibitor of HO activity, abolished the infarction-reducing effect of Bach1 disruption, indicating that reduction in the infarct size was mediated, at least in part, by HO-1 activity. Thus, Bach1 plays a pivotal role in setting the levels of both constitutive and inducible expression of HO-1 in the myocardium. Bach1 inactivation during I/R appears to be a key mechanism controlling the activation level of cytoprotective program involving HO-1.

Animals↗
PubMed2006

Differential impact of family history on age-associated increase in the prevalence of hypertension and diabetes in male Japanese workers.

Family history and aging are independent risk factors for the development of hypertension as well as for the development of diabetes. However, it is unclear how the family histories influence the rate of age-associated increase in these diseases. Moreover, despite the fact that hypertension and diabetes often occur concomitantly, it is not known whether family history of hypertension increases the risk of diabetes or vice versa. To gain an insight into these questions, we investigated the cross-sectional prevalence and family history of hypertension and diabetes in 1,123 male subjects (mean age, 42.1 +/- 12 years; range, 20-60 years) who participated in annual medical check-ups. The data were analyzed by 10-year age groups (20s, 30s, 40s and 50s). The prevalence of hypertension increased with age group either in the absence (12% in the 20s and 39% in the 50s) or in the presence (21% in the 20s and 59% in the 50s) of family history of hypertension, and thus the increasing rate of prevalence with age was not affected by family history. The prevalence of diabetes in the absence of family history of diabetes was low until the 40s (< 1.2%) but it jumped in the 50s (4.3%). On the other hand, in the presence of family history, the prevalence was 4% in the 20s and progressively increased to 20% in the 50s. The impact of family history on the risk of diabetes was strong and appeared to increase with age. Family history of hypertension did not increase the risk of diabetes, and family history of diabetes did not increase the risk of hypertension. These results suggest that family history of hypertension has an additive impact on the age-associated increase in the risk of hypertension, whereas family history of diabetes has an exponential impact on aging-associated increase in the risk of diabetes.

Adult↗
PubMed2005

Association of Helicobacter pylori infection with systemic inflammation and endothelial dysfunction in healthy male subjects.

OBJECTIVES: The goal of the present study was to determine whether seropositivity to Helicobacter pylori (HP), Chlamydia pneumoniae (CP), and cytomegalovirus (CMV) is associated with systemic inflammation and endothelial dysfunction in healthy male subjects. BACKGROUND: Chronic infection with certain bacteria and viruses may play an important role in inflammation as the pathogenesis of atherosclerosis. METHODS: The serum levels of immunoglobulin G antibodies to HP, CP, CMV, high-sensitivity C-reactive protein, soluble intercellular adhesion molecule-1, and soluble vascular cell adhesion molecule-1 were determined in 81 healthy Japanese men (40 +/- 10 years of age). High-frequency ultrasonographic imaging of the brachial artery was used to study endothelium-dependent (flow-mediated vasodilation) and endothelium-independent (nitroglycerin-induced) vasodilation. RESULTS: Prevalences of seropositive antibodies to HP, CP, and CMV were 67.9%, 61.7%, and 56.8%, respectively. Infection with HP, CP, or CMV had no relationship with age, blood pressure, or level of serum glucose, lipid, or soluble vascular cell adhesion molecule-1. The levels of C-reactive protein and soluble intercellular adhesion molecule-1 were significantly higher, and flow-mediated vasodilation was significantly lower in subjects with seropositive antibodies to HP than in subjects with seronegative antibodies to HP. Endothelium-independent vasodilation was similar in both groups. CONCLUSIONS: Chronic infection with HP may be involved in the development of the atherosclerosis via endothelial dysfunction and systemic and vascular inflammation.

Adult↗
PubMed2005

Effects of genetic ablation of bach1 upon smooth muscle cell proliferation and atherosclerosis after cuff injury.

Bach1 is a transcriptional repressor of the cytoprotective enzyme heme oxygenase-1 (HO-1). Although HO-1 protects against atherosclerosis, the function of Bach1 in this process is poorly understood. We isolated peritoneal macrophages and aortic smooth muscle cells (SMC) from wild-type and bach1-deficient mice. bach1-Deficient macrophages expressed increased levels of HO-1 and showed elevated phagocytic activity when incubated with 0.75 microm microspheres. In SMC, bach1-ablation resulted in increased expression of HO-1 and decreased proliferation in bromodeoxyuridine incorporation assay as compared with wild-type cells. The up-regulated phagocytic activity and reduced SMC proliferation of bach1-deficient cells were not restored by Zinc (II) protoporphyrin IX, an inhibitor of HO, suggesting that HO-independent mechanisms are also involved in the regulation of phagocytosis of macrophages and proliferation of SMC by Bach1. In wild-type mice, cuff placement around femoral artery caused pronounced intimal proliferation without affecting the media, thus resulting in intimal to medial (I/M) volume ratio of 65.6%. bach1-deficient mice had less degree of intimal growth (I/M ratio of 45.6%). These results indicate that Bach1 plays a critical role in the regulation of HO-1 expression, macrophage function, SMC proliferation and neointimal formation. Bach1 may regulate gene expression in these cells during inflammation and atherogenesis.

Animals↗
PubMed2005

Beneficial effect of T-type calcium channel blockers on endothelial function in patients with essential hypertension.

Endothelial function is impaired in essential hypertension. T-type but not L-type voltage-gated Ca2+ channels were detected in the vascular endothelium. The purpose of the present study was to clarify the role of T-type Ca2+ channels in endothelial function. We studied flow-mediated vasodilation (FMD) and sublingual nitroglycerin (NTG)-induced vasodilation in the brachial artery. Forty patients with essential hypertension were randomly assigned to treatment with efonidipine, a T- and L-type Ca2+ channel blocker, or with nifedipine, an L-type Ca2+ channel blocker. Twenty healthy normotensive individuals were included as a control group. In patients with essential hypertension, FMD was attenuated and NTG was similar that of compared to healthy controls. After 12 weeks, the decrease in mean blood pressure in the efonidipine and nifedipine groups were similar. The endothelial function index, a ratio of FMD/NTG, was significantly increased by efonidipine (73 +/- 24 to 94 +/- 20%) but unchanged by nifedipine. Urinary excretion 8-hydroxy-2'-deoxyguanosine (8-OHdG) and serum malondialdehyde-modified low-density lipoprotein (LDL) were decreased by efonidipine but unchanged by nifedipine. These results suggest that a T-type Ca2+ channel blocker, but not an L-type Ca2+ channel blocker, may improve vascular endothelial dysfunction in patients with essential hypertension via a reduction in oxidative stress.

Adult↗
PubMed2005

[Dopamine].

Explore the source record for details and available documents.

Adrenal Gland Neoplasms↗
PubMed2004

Telomere attrition in white blood cell correlating with cardiovascular damage.

Aging is a major risk factor for cardiovascular disease. Chronological aging does not always parallel biological aging, but there is no reliable biomarker for the latter. In the present study, we tested the hypothesis that telomere attrition in white blood cells is related to endothelial dysfunction and the extent of atherosclerosis, and thus may serve as a useful marker for biological aging. We evaluated telomere lengths in white blood cells by measuring the mean telomere restriction fragment length (mTRFL), as well as endothelial function by flow mediated dilatation (FMD) in the brachial artery, in patients with various degrees of cardiovascular damage and in normal subjects. Cardiovascular damage was assessed by a cardiovascular damage (CVD) score, with 1 point being given for the presence of each cardiovascular risk factor (hypertension, hyperlipidemia and diabetes) and for each event (angina, myocardial infarction, cerebrovascular event and peripheral vascular disease). Subset analysis of CVD score groups revealed that mTRFL and FMD decreased in the rank order of CVD score. Although mTRFL was inversely correlated with age, telomere index, defined as the ratio of TRFL to TRFL predicted by age, also decreased with increase in CVD score. These results indicate that telomere attrition in white blood cells is more closely associated with endothelial damage and atherosclerosis than is chronological aging, supporting the hypothesis that mTRFL in white blood cells is a useful marker for biological aging of the cardiovascular system.

Adult↗
PubMed2004

[Establishment of a clinical method for evaluating flow-mediated vasodilation(FMD) in brachial artery].

We have established a clinical routine method for evaluating the endothelial function in forearm circulation in humans. Flow-mediated vasodilation(FMD) was used as the endothelium-dependent and the response to nitroglycerin(NTG) as the endothelium-independent vasodilation. Diameter of the brachial artery was measured by high-frequency ultrasonographic imaging before and after hyperemia following artery occlusion. Because vasodilation reached the maximal level when the artery was occluded for 5 min, this time was selected as the occlusion time. FMD was greater (12 vs 9%) after upper-arm occlusion than after forearm occlusion. The peak time to maximal vasodilation was 50 sec after forearm occlusion and 70 sec after upper-arm occlusion. During NO synthesis inhibitor infusion, vasodilation after forearm occlusion was abolished, whereas that after upper-arm occlusion was attenuated by half. Therefore, the mechanisms for FMD may differ by occlusion position. The response to NTG was attenuated by aging. FMD was significantly decreased by coronary artery disease and coronary risk factors such as hypertension, hyperlipidemia and diabetes, but the response to NTG was not changed by these diseases. These measurements may offer useful tools for assessment of endothelial function.

Arteriosclerosis↗
PubMed2003

Disruption of the type 2 dopamine receptor gene causes a sodium-dependent increase in blood pressure in mice.

BACKGROUND: Dopamine D(2) receptors (D(2)Rs) are expressed in the kidney. It has not been determined whether D(2)Rs are involved in the mechanism of sodium handling and blood pressure (BP) control. METHODS: The function of D(2)Rs was investigated in mice disrupted with D(2)R gene (D(2)KO mice). Six-week-old male D(2)KO mice and wild-type (WT) mice were fed high-salt (4% NaCl) or low-salt (0.01% NaCl) diets for 8 weeks. RESULTS: Before starting the metabolic diet, there were no significant differences in body weight, food consumption, and 24-h urine excretions of creatinine, sodium and potassium. The high-salt diet caused a significant elevation in systolic BP in D(2)KO mice but not in WT mice. Calculation of sodium and potassium balances revealed a significantly high level of sodium retention in D(2)KO mice placed on the high-salt diet. Twenty-four-hour urine norepinephrine excretions and heart rates, indicators of sympathetic activity, were not different in D(2)KO and WT mice on the high-salt diet. Administration of nemonapride, a specific D(2)-like receptor antagonist, to WT mice given 0.9% NaCl in drinking water caused suppression of urinary sodium excretion but had no effect in mice without salt loading. CONCLUSIONS: These results suggest that D(2) receptors promote sodium excretion during a period of high salt intake. A defect in this mechanism may result in sodium-dependent BP elevation.

Animals↗
PubMed2003

Immunohistochemical distributions of the tissue kallikrein-kinin system in ischemic and non-ischemic mouse heart.

Kinins have been shown to play a cardioprotective role during myocardial ischemia. However, the localization of each of the components of the kallikrein-kinin system in the heart has not been determined in a cell type-specific manner. Recently, mK1 has been identified as the major tissue kallikrein with the strongest bradykinin-forming activity among the products of the mouse tissue kallikrein gene superfamily. In the study presented here, we investigated the localizations of mK1, kininogen and bradykinin B2 receptors (B2Rs) in ischemic and non-ischemic left ventricles by immunohistochemistry. Kininogen, which contains bradykinin as a surface epitope, was detected by an anti-bradykinin antibody. Changes in the amounts of mK1 and B2R were evaluated by Western blot analysis. Myocardial ischemia was induced by ligation of the left anterior descending coronary artery for 60 min followed by reperfusion for 24 h. mK1 and B2Rs were most abundantly expressed in the vascular endothelium and, to a lesser extent, in fibroblasts. No immunohistochemical signal of these molecules was detected in myocytes. Kininogen was localized in the vascular endothelium and the smooth muscle layer. Myocardial ischemia, although it had no effect on the localization of these molecules, increased the amounts of mK1 and B2R. We have obtained immunohistochemical evidence that all components of the tissue kallikrein-kinin system are present in the mouse heart. The coronary artery is the major site of kallikrein-kinin activity both in ischemic and non-ischemic hearts.

Animals↗
PubMed2003

Dopamine D2 receptor modulates sodium handling via local production of dopamine in the kidney.

We have recently demonstrated that a deletion of the dopamine D2 receptor gene caused suppression of urinary sodium excretion and salt-sensitive elevation of blood pressure in mice. In order to understand the mechanisms underlying this impaired sodium excretion, we studied renal dopamine production and dopamine-induced sodium excretion in 20- to 30-week-old male D2-receptor knockout (D2KO) mice and age- and sex-matched wildtype (WT) mice. Renal local dopamine synthesis, examined by 24-h urine free dopamine excretion (UDAV), was significantly (p < 0.05) reduced in D2KO mice compared to that in WT mice (D2KO versus WT: 1.06 +/- 0.2 versus 1.5 +/- 0.3 ng/mg creatinine). Such a difference between D2KO and WT mice was also observed after oral administration of 3,4-dihydroxyphenylalanine (L-DOPA), a precursor of dopamine, at 5 mg/kg per day for 24 h. Furthermore, activity of aromatic 1-amino acid decarboxylase, a dopamine synthetase, was significantly suppressed in D2KO mice. Next, we examined changes in 24-h urine flow (UV) and 24-h sodium excretion (UNaV) during chronic infusion of dopamine at sub-pressor doses (3-4 microg/kg per min, sq.) or a vehicle via an osmotic pump. Urine flow in 24 h and UNaV were significantly (p < 0.05) smaller in D2KO mice infused with vehicle than in WT mice infused with vehicle (UV: 210 +/- 43 versus 650 +/- 163 microl/day; UNaV: 20.6 +/- 13.2 versus 44.4 +/- 21.6 microEq/day). After administration of dopamine, UV and UNaV in D2KO mice were restored to a level similar to that in WT mice. These results indicate that D2-dopamine receptors play a significant role in renal local dopamine synthesis and that a shortage of dopamine was, at least in part, responsible for the suppression of UV and UNaV in D2KO mice. However, we could not conclude from the present study whether renal tubular sodium reabsorption is intact in D2KO mice because the baseline dopamine contents in kidneys of D2KO mice and WT mice may be different.

Administration, Oral↗
PubMed2003

Cardiac angiotensin II type 2 receptor activates the kinin/NO system and inhibits fibrosis.

We have previously demonstrated that stimulation of the angiotensin (Ang) II type 2 receptor in vascular smooth muscle cells caused bradykinin production by activating kininogenase in transgenic mice. The aim of this study was to determine whether overexpression of AT2 receptors in cardiomyocytes attenuates Ang II-induced cardiomyocyte hypertrophy or interstitial fibrosis through a kinin/nitric oxide (NO)-dependent mechanism in mice. Ang II (1.4 mg/kg per day) or vehicle was subcutaneously infused into transgenic mice and wild-type mice for 14 days. The amount of cardiac AT2 receptor relative to AT1 receptor in transgenic mice was 22% to 37%. Ang II caused similar elevations in systolic blood pressure (by approximately 45 mm Hg) in transgenic mice and wild-type mice. Myocyte hypertrophy assessed by an increase in myocyte cross-sectional area, left ventricular mass, and atrial natriuretic peptide mRNA levels were similar in transgenic and wild-type mice. Ang II induced prominent perivascular fibrosis of the intramuscular coronary arteries, the extent of which was significantly less in transgenic mice than in wild-type mice. Inhibition of perivascular fibrosis in transgenic mice was abolished by cotreatment with HOE140, a bradykinin B2 receptor antagonist, or L-NAME, an inhibitor of NO synthase. Cardiac kininogenase activity was markedly increased (approximately 2.6-fold, P<0.001) after Ang II infusion in transgenic mice but not in wild-type mice. Immunohistochemistry indicated that both bradykinin B2 receptors and endothelial NO synthase were expressed in the vascular endothelium, whereas only B2 receptors were present in fibroblasts. These results suggest that stimulation of AT2 receptors present in cardiomyocytes attenuates perivascular fibrosis by a kinin/NO-dependent mechanism. However, the effect on the development of cardiomyocyte hypertrophy was not detected in this experimental setting.

Angiotensin II↗
PubMed2003

Effect of amlodipine and cilazapril treatment on platelet Ca2+ handling in spontaneously hypertensive rats.

Abnormal Ca2+ handling and enhanced aggregation response have been reported in platelets from spontaneously hypertensive rats (SHR) and patients with essential hypertension, and thought to be involved in the progression of target organ damage of hypertension. It is important to examine whether antihypertensive therapy can improve the abnormal platelet response in hypertension. We investigated the effect of antihypertensive treatment such as amlodipine and cilazapril on Ca2+ handling and aggregation response in SHR platelets. Four-week-old male SHR were divided into three groups. Each group was treated with amiodipine (A: 10 mg/kg/day), cilazapril (C: 10 mg/kg/day) or vehicle (V) for 8 weeks by gavage. At 12-week-old, platelet [Ca2+]i was measured with fura-2 in each group of SHR and age-matched Wistar-Kyoto rats (WKY) as normal control. Systolic blood pressure in amlodipine and cilazapril treated groups were similar with WKY and significantly lower than vehicle treated group (A: 124 +/- 9, C: 126 +/- 9, WKY: 122 +/- 10 and V: 180 +/- 9 mmHg, respectively). The basal [Ca2+]i in the three groups of SHR were similar and higher than WKY (A: 47 +/- 1.7, C: 47 +/- 1.2, V: 48 +/- 3.9 and WKY: 40 +/- 4.0 nmol/l, respectively). There were no significant differences in thrombin (0.1 U/ml)-stimulated [Ca2+]i rise in the presence or absence of extracellular Ca2+ among the three groups of SHR and these were higher than WKY. Intracellular Ca2+ discharge capacity, assessed by the ionomycinstimulation was similar in the all groups. Thrombin-induced maximum platelet aggregation responses in the three groups of SHR were similar and higher than WKY. The antihypertensive treatment of Ca2+ antagonist or ACE inhibitor gave no change in intraplatelet Ca2+ metabolism in SHR. These results support the hypothesis that an abnormal Ca2+ handling in SHR platelet is genetically determined and not improved by hypotensive therapy.

Amlodipine↗
PubMed2002

Cardioprotective role of AT2 receptor in postinfarction left ventricular remodeling.

The aim of this study was to determine the role of the AT2 receptor (AT2R) in left ventricular (LV) remodeling after myocardial infarction (MI). The left anterior descending arteries were ligated in AT2R gene knockout (Agtr2-) and wild-type (Agtr2+) mice. The LV remodeling was evaluated by echocardiography and histology over a period of 2 weeks after MI. The infarct sizes in hearts excised from Agtr2+ and Agtr2- mice on day 1 were similar. The mortality rate of Agtr2- mice (62.9%) on day 14 after MI was significantly (P<0.05) higher than that of Agtr2+ mice (39.7%). Accordingly, LV/body weight ratios (3.7+/-0.2 versus 3.0+/-0.1 on day 14) and LV end-diastolic (4.8+/-0.3 versus 3.9+/-0.4 mm on day 7) and end-systolic (4.4+/-0.3 versus 3.2+/-0.6 mm on day 7) dimensions evaluated by echocardiography were significantly greater in Agtr2- than in Agtr2+ mice. The rates of ventricular arrhythmia, rates of cardiac rupture, and blood pressures in the 2 strains were similar after MI. Myocyte cross-sectional areas were increased after MI, but the magnitudes were similar in Agtr2+ and Agtr2- mice, indicating the greater increases in LV dimensions and weight in Agtr2- mice are due to elongation of myocyte length and/or an increase in the interstitial weight (including vasculatures, infiltrated cells, and interstitial fluid). Interstitial fibrosis in remote myocardium was not evident in either strain. These results indicate AT2R plays a significant role in the protection against early development of LV dilation, thereby reducing the early mortality rate after MI.

Animals↗
PubMed2002

Estrogen replacement suppresses function of thrombin stimulated platelets by inhibiting Ca(2+) influx and raising cyclic adenosine monophosphate.

OBJECTIVE: Estrogen replacement therapy (ERT) in postmenopausal women reduces the risk of cardiovascular diseases. Beneficial changes in lipid profiles account for only one part, thereby raising the question of other estrogen induced benefit that may be lost at menopause. The purpose of this study was to determine the effects of estrogen replacement therapy (ERT) on platelet function of postmenopausal women. METHODS: The effect of 4 weeks ERT (conjugated estrogens 0.625 mg/day) on platelet function was evaluated ex vivo in 18 postmenopausal women (mean age 53 +/- 5 years, after menopause 3.8 +/- 1.9 years). RESULTS: After ERT, (1) plasma concentrations of estrone and estradiol significantly increased (estrone: 16 +/- 7-211+/- 80 pg/ml, estradiol: 14+/- 3-125 +/- 49 pg/ml, P<0.05) and LDL-cholesterol decreased (129 +/- 23-94 +/- 25 mg/dl, P<0.05). Plasma 6-keto-PG F(1) alpha significantly increased (7.2 +/- 3.4-13.3 +/- 6.7 pg/dl, P<0.05). (2) platelet aggregation and positive staining for P-selectin in thrombin- (0.1 and 1.0 U/ml) stimulated platelets were inhibited (Th 0.1 U/ml: 4.0 +/- 0.9-2.4 +/- 1.0/control, P<0.05), but positive staining for GP IIb-IIIa complex did not alter significantly. (3) Ca(2+) influx induced by thrombin decreased (Th 0.3 U/ml: 345 +/- 29-298 +/- 24 nmol/l, P<0.05). The baseline [Ca(2+)](i), the release of Ca(2+) from internal stores induced by thrombin and the size of internal Ca(2+) stores did not alter. (4) platelet c-AMP increased (Th 0.3 U/ml: 66.4 +/- 9.4-82.6 +/- 13.0 fmol/l, P<0.05), but platelet nitrite/nitrate (NO(x)) or c-GMP did not alter significantly. CONCLUSIONS: These results suggest that modulation of platelet function by decreasing Ca influx and increased production of c-AMP may account in part for the cardiovascular benefit of ERT.

Blood Platelets↗
PubMed2002

A frameshift mutation of beta subunit of epithelial sodium channel in a case of isolated Liddle syndrome.

BACKGROUND: Liddle syndrome is an autosomal dominant form of salt-sensitive hypertension caused by mutations in the epithelial sodium channel expressed in the distal nephron playing an essential role in Na absorption. All reported mutations in Liddle syndrome are either missense mutations or frameshift mutations destroying the PY motif closer to the C-terminus of the beta or gamma subunits causing the situation that the epithelial sodium channels are not degraded and sodium is pooled and thus hypertension and hypokalemia are caused. METHODS: We sequenced the C-terminus of the beta or gamma subunits of the epithelial sodium channel in a Japanese family of a patient clinically diagnosed as having Liddle syndrome. RESULTS: As a result, we found in the proband, a frameshift mutation of the beta subunit caused by a single cytosine insertion at the codon 595, introducing a new stop codon at 605 and deleting the last 34 amino acids from the normally encoded protein. CONCLUSION: This mutation is carried by neither parent (with paternity proven) and hence confirms this has occurred as a event within this family.

Adolescent↗