Urinary levels of cortisol but not catecholamines are associated with those of 8-hydroxy-2'-deoxyguanosine in uncomplicated primary hypertension.

OBJECTIVES: The relationships between stress hormones and oxidative DNA damage have not yet been explored in human hypertension. We investigated the associations of urinary levels of cortisol or catecholamines with those of 8-hydroxy-2'-deoxyguanosine, a marker of oxidative DNA damage in primary hypertension. METHODS: Untreated 156 primary hypertensives without apparent cardiovascular diseases were entered into the study. Following blood sampling after an overnight fast, 24-h blood pressure monitoring and 24-h urinary sampling were performed simultaneously to determine 24-h averaged values for blood pressure and urinary levels of cortisol, catecholamines and 8-hydroxy-2'-deoxyguanosine. RESULTS: Urinary cortisol significantly correlated positively with urinary 8-hydroxy-2'-deoxyguanosine in all studied participants (r = 0.334, P < 0.001). Contrary, either urinary adrenaline or urinary noradrenaline did not significantly correlate with urinary 8-hydroxy-2'-deoxyguanosine (r = 0.050, P = 0.553 or r = 0.063, P = 0.435). Additionally, the positive association of urinary cortisol with urinary 8-hydroxy-2'-deoxyguanosine remained highly significant after the adjustments for multiple confounders of oxidative stress such as age, gender, body mass index, smoking status, 24-h blood pressure, C-reactive protein and estimated glomerular filtration rate (partial r = 0.323, P < 0.001), although only approximately 10% of the variance in urinary cortisol was attributable to differences in urinary 8-OHdG (partial r2 = 0.104). Thus, our data indicate that cortisol but not catecholamines could at least partially contribute to the occurrence of oxidative DNA damage in primary hypertensives. CONCLUSION: The present study suggested the possibility that the overactivation of hypothalamic-pituitary-adrenal axis rather than sympathoadrenal system could enhance oxidative stress and attendant DNA oxidation in uncomplicated primary hypertension.

Factors Associating with Non-Dipping Pattern of Nocturnal Blood Pressure in Patients with Essential Hypertension.

Background: In patients with essential hypertension, a non-dipping blood pressure pattern is a strong risk factor for cardiovascular diseases. However, background factors associating with such a blood pressure pattern remain unknown. Methods: Untreated essential hypertensive patients without chronic kidney diseases who were admitted to our outpatient clinic were included. Blood sampling and 24 h ambulatory blood pressure monitoring were mandatorily performed. Non-dipper status was defined as a maximum decrease in nocturnal systolic blood pressure within 10%. Clinical factors associating with non-dipper status were investigated. Results: A total of 154 patients (56 ± 12 years old, 86 men) were included. Among baseline characteristics, a higher serum uric acid level was independently associated with non-dipper status (odds ratio 1.03, 95% confidence interval 1.00−1.05, p < 0.05). Among those with non-dipper status, a higher high-sensitivity C-reactive protein level tended to be associated with incremental nighttime systolic blood pressure levels (p = 0.065). Conclusions: Hyperuricemia and micro-inflammation might be associated with attenuated nocturnal blood pressure dipping and incremental nighttime systolic blood pressure levels.

Plasma and Urinary Levels of Nerve Growth Factor Are Elevated in Primary Hypertension.

Nerve growth factor (NGF) is the main neurotrophic factor that can control sympathetic nerve innervation and sympathetic neural activity in cardiovascular organs. Although NGF overproduction and its influences on the sympathetic nervous system have been shown in hypertensive animals, NGF status and its association with sympathetic nerve activity have not yet been explored in human hypertension. In the present study, therefore, plasma and urinary levels of NGF and those of catecholamines (i.e., indices for NGF status and sympathoadrenal activity, respectively) were compared between 83 untreated primary hypertensives without apparent cardiovascular damages and 81 healthy normotensive subjects. Plasma and urinary levels of NGF were significantly greater in the hypertensive group (311 ± 158 pg/mL and 72.7 ± 54.0 ng/g of Cr) than in the normotensive group (168 ± 188 pg/mL and 54.5 ± 38.8 ng/g of Cr) (p < 0.05 for each measurement), even if the baseline differences of age and gender between the groups were adjusted. Similarly, plasma and urinary levels of catecholamines were significantly higher in the hypertensive group than in the normotensive group except for plasma noradrenaline. In addition, despite no significant correlations between plasma levels of NGF and catecholamines in both groups, urinary NGF significantly correlated positively with both urinary noradrenaline and urinary adrenaline in the hypertensive group (r = 0.259, p=0.018 and r = 0.232, p=0.035), but not in the normotensive group (r = 0.115, p=0.307 and r = -0.018, p=0.871). On the contrary, plasma and urinary levels of NGF as well as those of catecholamines did not associate with any systemic hemodynamic indices such as blood pressure and pulse rate in either group. Thus, primary hypertension was characterized by the enhancements of both NGF status and sympathoadrenal activity and the positive relationship between them. Our data indicate that enhanced NGF status and subsequent NGF-induced sympathoadrenal overactivity could occur in primary hypertension.

Impact of Geriatric Nutritional Risk Index and Modified Creatinine Index Combination on Mortality in Hemodialysis Patients.

The prognostic impact of the combination of a geriatric nutritional risk index (GRNI) and modified creatinine index, both of which assess nutritious status in hemodialysis patients, has not yet been well investigated thus far. Patients receiving maintenance hemodialysis in our institutes between February 2011 and January 2017 were retrospectively included. The baseline GRNI and modified Creatinine index were calculated and the impact of their combination on 5-year all-cause mortality following the index hemodialysis was investigated. A total of 183 patients (68.3 ± 12.4 years, 98 men, hemodialysis duration 97 ± 89 months) were followed from the index hemodialysis for 5.5 years. Mean GNRI was 91.2 and mean modified Creatinine index was 22.2 in men and 19.6 in women. The 5-year survival was significantly stratified by the median values of GNRI and modified Creatinine index (p < 0.05 for both). Patients with low GNRI and a low modified Creatinine index had lower 5-year survival than those with the other three combination patterns (p < 0.05). A combination of GNRI and modified Creatinine index may be a promising tool to risk stratify mortality in dialysis patients.

Urinary Angiotensinogen Could Be a Prognostic Marker of the Renoprotection of Olmesartan in Metabolic Syndrome Patients.

This study was performed to demonstrate urinary angiotensinogen as a potential prognostic marker of the albuminuria reduction effects of olmesartan in patients with metabolic syndrome. In 24 patients (eight women, 57.88 ± 2.00 years), 5-40 mg/day of olmesartan were given. Urinary concentrations of albumin and angiotensinogen (normalized by urinary concentrations of creatinine) and plasma renin activity were measured before and after the 12- and 24-week marks of olmesartan treatment. Olmesartan treatment increased plasma renin activity and decreased urinary albumin and urinary angiotensinogen significantly (p < 0.05). Based on the % change in urinary albumin, patients were divided into two groups, responders (<-50%) and non-responders (≥-50%), and a logistic analysis of urinary angiotensinogen before treatment showed the area under the curve as 0.694. When the cutoff value of urinary angiotensinogen before the treatment of 13.9 µg/g Cr was used, the maximum Youden index (0.500, specificity: 11/12 = 91.7% and sensitivity: 7/12 = 58.3%) was obtained. When all patients were re-divided into two groups, those with higher values of urinary angiotensinogen before the treatment (Group H, n = 16) and those with lower values, Group H showed significantly decreased urinary albumin (p < 0.05). Therefore, urinary angiotensinogen could be a prognostic marker of the albuminuria reduction effects of olmesartan in patients with metabolic syndrome.

Pubertal administration of antiserum against nerve growth factor regresses renal vascular remodeling in spontaneously hypertensive rats.

To investigate the role of nerve growth factor (NGF) in the development of hypertensive renal vascular remodeling, antiserum against NGF (anti-NGF) or vehicle was injected at 3 weeks of age in spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats (n = 9 for each treatment in each strain). Flow-pressure (F-P) and pressure-glomerular filtration rate (P-GFR) relationships at vasodilated perfused kidneys were determined at 10 weeks of age. In the vehicle rats, blood pressure, renal noradrenaline content, the gradient of F-P (minimal vascular resistance at pre- and post-glomerular vasculature) and the X-intercept of P-GFR (preglomerular : postglomerular vascular resistance ratio) were greater in SHR than in WKY rats, although the gradient of P-GFR (glomerular filtration capacity) did not differ significantly between the strains. Blood pressure and renal noradrenaline content were lower in SHR receiving anti-NGF than in SHR receiving vehicle, although such difference was not observed in WKY rats. The gradient of F-P was less but the gradient of P-GFR was greater in SHR receiving anti-NGF compared with SHR receiving vehicle, although the similar differences did not occur in WKY rats. Blood pressure and renal noradrenaline content remained greater in SHR treated with anti-NGF compared with WKY rats treated with vehicle; however, the gradient of F-P did not differ significantly between them. Contrary, anti-NGF did not affect the X-intercept of P-GFR in either strain. In conclusion, NGF could contribute to the genesis of renal vascular remodeling, at least in part, through modification of renal sympathetic activity and blood pressure in SHR.

Increased levels of small dense low-density lipoprotein cholesterol associated with hemorheological abnormalities in untreated, early-stage essential hypertensives.

Among subfractions of low-density lipoprotein cholesterol (LDL-C), small dense LDL-C (SdLDL-C) has been highlighted as the most atherogenic lipoprotein cholesterol. The present study aimed to compare the relationship of SdLDL-C with blood viscosity, a surrogate marker for cardiovascular disease, with that of other lipid fractions with blood viscosity in essential hypertensives (EHTs). In 128 untreated, early-stage EHTs, blood viscosity was measured with a falling-ball microviscometer, and serum levels of lipid fractions were determined. Blood and plasma viscosity was significantly higher in 49 patients with dyslipidemia (fasting serum level of LDL-C > 140 mg dl(-1), triglyceride > 150 mg dl(-1) or high-density lipoprotein cholesterol (HDL-C) < 40 mg dl(-1)) compared with 79 patients without dyslipidemia, although hematocrit and RBC rigidity index 'k' did not differ between the two groups. Together, SdLDL-C, LDL-C, triglyceride and large LDL-C were positively correlated with blood viscosity, but for HDL-C, the correlation was negative. After adjusting for non-lipid variables that correlated with blood viscosity (that is, the age, body mass index, resting diastolic blood pressure, sex, hematocrit, plasma viscosity and homeostasis model of assessment of insulin resistance), SdLDL-C was most strongly associated with blood viscosity among the lipid fractions. These data suggest that SdLDL-C could strongly increase blood viscosity in EHTs.

Renal vascular structural properties and their alterations by removal of uraemic toxins in a rat model of chronic kidney disease.

1. Renal vascular structural properties and their alterations by removal of uraemic toxins with AST-120, an oral adsorbent, were examined in subtotal nephrectomized rats. 2. Eight- or 9-week-old Sprague-Dawley rats received 3/4 nephrectomy (n = 18) and thereafter were fed 24.5% protein diet with (AST; n = 9) or without (AST-; n = 9) AST-120 (0.4 g/100 g bodyweight). Sham-operated rats (Sham; n = 9) received the diet without AST-120. At 21-22 weeks of age, flow-pressure (F-P) and pressure-glomerular filtration rate (P-GFR) relationships were determined for maximally vasodilated, perfused kidneys. 3. The gradient of F-P (minimal renal vascular resistance reflecting the overall luminal dimensions of pre- and post-glomerular vasculature) was lower in AST- than Sham rats. In contrast, the x-intercept (preglomerular : post-glomerular vascular resistance ratio) and gradient (glomerular filtration capacity) of P-GFR did not differ between the two groups. The vascular wall and lumen at the interlobular arteries were greater in AST- than Sham rats. 4. Although the vascular wall and lumen at the interlobular arteries were less in AST than in AST- rats, the gradient of F-P and the x-intercept of P-GFR did not differ between the two groups. In contrast, the glomerular filtration capacity was greater in AST than AST- rats. 5. In conclusion, the lumen of both pre- and post-glomerular resistance vessels increased and glomerular filtration capacity failed to increase in subtotal nephrectomized rats. Uraemic toxins could play an important role in the development of structural alterations in glomeruli rather than renal resistance vessels in chronic kidney disease.

Imbalance of renal production between 5-hydroxytryptamine and dopamine in patients with essential hypertension complicated by microalbuminuria.

BACKGROUND: In the kidney, 5-hydroxytryptamine (5-HT) and dopamine (DA) are formed by the same enzyme, l-aromatic amino acid decarboxylase, but act on renal function and glomerular structure in an opposite direction. The present study was designed to explore whether rates of renal production of 5-HT relative to that of DA are altered in patients with essential hypertension and microalbuminuria. METHODS: We measured urinary levels of 5-HT and DA, reflecting renal production of 5-HT and DA as well as 24-hour ambulatory blood pressure and urinary albumin excretion in 82 consecutive untreated, essential hypertensives without overt proteinuria. RESULTS: Urinary 5-HT excretion and the ratio of urinary 5-HT to DA were significantly higher in 22 patients with microalbuminuria than in the remaining patients with normoalbuminuria, although urinary DA levels did not differ between the groups. The 24-hour systolic and diastolic blood pressures were also higher in the microalbuminuric group than in the normoalbuminuric group. Multiple regression analysis revealed that urinary 5-HT excretion and 24-hour systolic blood pressure were independently associated with urinary albumin excretion. Furthermore, urinary 5-HT excretion was positively correlated with creatinine clearance as well as blood pressure but tended to be negatively correlated with fractional excretion of sodium. CONCLUSIONS: Renal production of 5-HT is enhanced compared with that of DA in essential hypertensives with microalbuminuria. This imbalance may contribute to the genesis of hypertensive glomerular damage.

Increased blood viscosity is associated with reduced renal function and elevated urinary albumin excretion in essential hypertensives without chronic kidney disease.

Increased blood viscosity reduces blood flow and elevates vascular resistance in the cardiovascular system. The aim of this study was to elucidate how blood viscosity could affect renal function and eventually contribute to renal damage in essential hypertensives (EHT). In 164 untreated EHT without apparent renal damage (96 men, 56±12 years old, creatinine clearance 123±33 ml min(-1) per 1.73 m(2) and urinary albumin excretion 19±19 mg per day), blood and plasma viscosity was determined using a falling ball microviscometer. Blood viscosity correlated negatively with creatinine clearance (r=-0.185, P=0.018) and positively with urinary albumin excretion (r=0.253, P=0.001). This indicated that increased blood viscosity is associated with reduced renal function and worsening of albuminuria in EHT. Stepwise multiple regression analysis identified blood viscosity as an independent determinant of creatinine clearance (R(2)=0.058) and urinary albumin excretion (R(2)=0.216). In conclusion, increased blood viscosity may be a risk for development of renal disease in EHT.

Blood rheology and platelet function in untreated early-stage essential hypertensives complicated with metabolic syndrome.

We examined whether hemorheology and platelet function are affected in essential hypertensives (EHTs) of the World Health Organization stage I when complicated with metabolic syndrome (Mets). In 156 untreated EHTs, blood viscosity and platelet surface markers were determined. Blood viscosity was significantly elevated in 54 subjects with Mets compared with 102 subjects without Mets. Hematocrit and plasma viscosity increased in the group with Mets, although red blood cell rigidity index "k" did not differ between groups. As a whole group, blood viscosity correlated positively with hematocrit and plasma viscosity. Additionally, plasma viscosity correlated positively with plasma leptin, triglyceride, homeostasis model assessment index, C-reactive protein, and plasma fibrinogen, but negatively with high-density lipoprotein cholesterol. In contrast, no differences were seen in platelet surface markers between groups. In conclusion, EHTs of the early stage complicated with Mets are characterized by increased blood viscosity due to hemoconcentration and increased plasma viscosity.

[Case of distal renal tubular acidosis complicated with renal diabetes insipidus, showing aggravation of symptoms with occurrence of diabetes mellitus].

We report herein a 27-year-old male case of inherited distal renal tubular acidosis complicated with renal diabetes insipidus, the symptoms of which were aggravated by the occurrence of diabetes mellitus. At 2 months after birth, he was diagnosed as having inherited distal renal tubular acidosis and thereafter supplementation of both potassium and alkali was started to treat his hypokalemia and metabolic acidosis. At the age of 4 years, calcification of the bilateral renal medulla was detected by computed tomography. Subsequently his urinary volume gradually increased and polyuria of approximately 4 L/day persisted. At the age of 27 years, he became fond of sugar-sweetened drinks and also often forgot to take the medicine. He was admitted to our hospital due to polyuria of more than 10 L day, muscle weakness and gait disturbance. Laboratory tests disclosed worsening of both hypokalemia and metabolic acidosis in addition to severe hyperglycemia. It seemed likely that occurrence of diabetes mellitus and cessation of medications can induce osmotic diuresis and aggravate hypokalemia and metabolic acidosis. Consequently, severe dehydration, hypokalemia-induced damage of his urinary concentration ability and enhancement of the renin angiotensin system occurred and thereby possibly worsened his hypokalemia and metabolic acidosis. As normalization of hyperglycemia and metabolic acidosis might have exacerbated hypokalemia further, dehydration and hypokalemia were treated first. Following intensive treatment, these abnormalities were improved, but polyuria persisted. Elevated plasma antidiuretic hormone (12.0 pg/mL) and deficit of renal responses to antidiuretic hormone suggested that the polyuria was attributable to the preexisting renal diabetes insipidus possibly caused by bilateral renal medulla calcification. Thiazide diuretic or nonsteroidal anti-inflammatory drugs were not effective for the treatment of diabetes insipidus in the present case.

Roles of PDGF receptor-beta in the structure and function of postnatal kidney glomerulus.

BACKGROUND: Mesangial cell functions are critically regulated by platelet-derived growth factor receptor (PDGFR)-ß signals. In contrast to the well-established role of PDGFR-ß in the development of kidney glomerulus, its role in adult kidney glomerulus remains controversial. METHODS: We deleted the PDGFR-ß gene postnatally using the Cre-loxP system and analysed the long-term effects of PDGFR-ß inhibition on glomerular changes associated with ageing and subtotal nephrectomy. RESULTS: Mice depleted of PDGFR-ß (Deletant) survived without showing apparent abnormalities. In glomerulus of Deletant, mesangial PDGFR-ß expression was decreased. The glomerular cell numbers were low, and the ageing-associated increment of mesangial matrix area was suppressed in Deletant as compared with control mice with conserved PDGFR-ß expression (Floxed) at 48 weeks of age. At 2 weeks after subtotal nephrectomy, albuminuria and the elevation of blood urea nitrogen were aggravated in Deletant. At this time, Deletant showed specific glomerular changes that included many hypertrophic podocytes and collapsed capillaries. At 12 weeks after subtotal nephrectomy, the kidney function in Deletant restored to the level of Floxed; however, the Deletant glomeruli showed dilated capillaries, decreased cell number and reduced mesangial matrix area with less extended mesangial cell processes as compared with Floxed. CONCLUSIONS: The long-term inhibition of mesangial PDGFR-ß prevented age-related mesangial expansion. On the other hand, the kidney glomeruli with decreased PDGFR-ß showed increased vulnerability to the acute nephron loss, and showed mesangial insufficiency in the following adaptive process.

[Case of bladder pheochromocytoma with familial clustering].

We report herein a rare female case of bladder pheochromocytoma with familial clustering. Her mother had received an operation for bladder pheochromocytoma. When the present case was 20 years of age, body weight loss and fever appeared. Thereafter, nausea, vomiting and palpitation occurred especially at urination, and hypertension and tachycardia emerged. She was referred to our hospital for a further check up of hypertension at the age of 28 years. Her blood pressure was 176/130 mmHg, and pulse rate, 103/min. Hemorrhage and hard exudate were observed at the optic fundi. Twenty-four-hour ambulatory blood pressure monitoring disclosed that her hypertension was characterized by non-dipper type features and transient increases in both blood pressure and pulse rate occurring, especially at urination. Plasma noradrenalin level (14,399 pg/mL)was remarkably elevated, although the plasma adrenalin level (52 pg/mL) was within the normal limits. Computed tomography (CT) showed a mass lesion (7 cm in diameter) with central necrosis in the urinary bladder. 123I-MIBG showed strong uptake in the mass detected by CT. Venous blood sampling disclosed that the plasma noradrenalin concentration was highest at the lower level of the inferior vena cava. Therefore, a diagnosis of bladder pheochromocytoma with familial clustering was made and the pheochromocytoma was surgically removed.

[Autopsy case of Henoch-Schönlein purpura nephritis complicated with intestinal cytomegalovirus infection].

A 55-year-old man was admitted to our hospital because of arthralgia, purpura, abdominal pain, melena and leg edema. Laboratory findings showed an increased serum creatinine level (2.4 mg/dL), hematuria and massive proteinuria (10.7 g/day). Renal biopsy revealed diffuse endocapillary proliferation and focal mesangial proliferation with IgA deposition predominantly in the glomerular capillary walls. Based on these findings, he was diagnosed as having Henoch-Schönlein purpura nephritis and steroid therapy was started. Following steroid therapy, his nephrotic state remained unchanged, although his renal function improved concomitantly with the disappearance of arthralgia, purpura and abdominal symptoms. Therefore, cyclosporine was added to the steroid therapy to enhance immunosuppression. However, melena recurred and anemia progressed. Endoscopy revealed multiple ulcers in the duodenum and jejunum, and clipping was performed at some bleeding sites. However, he died of hemorrhagic shock. The autopsy revealed that hemorrhagic lesions having cytomegalovirus infection spread widely in the stomach, duodenum and jejunum. Recurrence of gastrointestinal bleeding during the treatment of Henoch-Schönlein purpura nephritis is usually due to severe vasculitis or steroid ulcer. However, in patients receiving strong immunosuppressive therapy, cytomegalovirus infection needs to be considered as cause of gastrointestinal bleeding.

Effects of uninephrectomy on renal structural properties in spontaneously hypertensive rats.

1. To investigate effects of a reduction in nephron numbers on renal structural properties in hypertension, either unilateral nephrectomy (UNX) or sham operation (SO) was performed at 5 weeks of age in spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats (n = 9 for each operation for each strain). 2. At 10-12 weeks of age, flow-pressure (F-P) and pressure-glomerular filtration rate (P-GFR) relationships were determined for maximally vasodilated, perfused kidneys. Kidneys were then perfusion fixed for histological analysis. 3. In the SO groups, the slope of F-P (minimal renal vascular resistance, reflecting overall luminal dimensions of pre- and post-glomerular vasculature) was greater in SHR than in WKY rats. The threshold pressure for beginning filtration at P-GFR (preglomerular to post-glomerular vascular resistance ratio) was higher in SHR than in WKY rats, but the slope of P-GFR (glomerular filtration capacity) did not differ between the two strains. These results suggest that vascular narrowing occurred, especially in the preglomerular resistance vessels in the kidneys of SHR, although glomerular filtration capacity was normal. 4. In UNX animals, the following results were obtained: (i) the slope of F-P was not affected in either strain; (ii) the pressure for beginning filtration at P-GFR was unchanged in WKY rats, but was decreased in SHR; (iii) the slope of P-GFR increased in WKY rats, but a compensatory adaptive increase was missing in SHR; and (iv) histologically, small increases in the luminal cross-sectional area of interlobular arteries and glomerular tuft area were observed in both strains. However, the increase in vascular lumen was more pronounced in SHR, whereas glomerular enlargement was greater in WKY rats. 5. These results suggested that UNX attenuates vascular narrowing of the preglomerular resistance vessels and glomerular structural adaptations to UNX (i.e. increased filtering capacity and glomerular enlargement) are impaired in SHR.

Angiotensin-converting enzyme-gene polymorphism is associated with collagen I synthesis and QT dispersion in essential hypertension.

AIM: This study tested the hypothesis that abnormal QT dispersion, an indicator of arrhythmogenic risk, is associated with angiotensin-converting enzyme (ACE) gene polymorphism and abnormalities of collagen metabolism. METHODS: A total of 132 patients with untreated essential hypertension (EHT) were recruited. QT dispersion corrected by heart rate (QTc) on a 12-lead electrocardiogram, ACE genotype, left ventricular mass index (LVMI) and E/A ratio using echocardiogram, plasma ACE activity and serum propeptide type I C-terminal procollagen (PICP) concentration, a marker of myocardial fibrosis, were determined. A normal control group (NC) of 200 normotensive subjects was used for comparison of QT dispersion. RESULTS: Number of EHT patients with ACE genotype I/I, I/D and D/D was 61, 52 and 19, respectively. LVMI and E/A ratio were similar in the three groups. Compared with subjects with I/I or I/D genotype, subjects with D/D showed higher plasma ACE activity (I/I: 13 +/- 0.6, I/D: 17 +/- 0.9, and D/D: 21 +/- 1.1 nmol/min per ml, mean +/- SE, P05) and serum PICP concentration (I/I: 106 +/- 5.4, I/D: 106 +/- 4.9, D/D: 140 +/- 12.1 ng/ml, P < 0.01). QTc dispersion was larger in the three hypertensive subgroups than in NC, and was the largest in EHT with D/D (NC: 0.037 +/- 0.001, I/I: 0.056 +/- 0.003, I/D: 0.055 +/- 0.002, D/D: 0.069 +/- 0.004 s, P < 0.05). CONCLUSION: ACE D/D genotype could be associated with an elevation of serum PICP concentration possibly leading to myocardial fibrosis and increased QT dispersion.

Relation of circulating blood volume to left ventricular geometry in essential hypertension.

To investigate whether circulating blood volume contributes to left ventricular (LV) geometry, 60 outpatients with untreated, mild to moderate essential hypertension and 45 normotensives were studied. Based on echocardiographic LV mass index and relative wall thickness, four patterns of LV geometry, i.e., normal left ventricle, concentric remodeling, eccentric hypertrophy and concentric hypertrophy, were identified. Plasma volume and blood volume were measured by the 131I labeled human serum albumin technique. LV end-diastolic volume was greater in patients with eccentric hypertrophy than in the groups of patients with normal left ventricles, concentric remodeling, or concentric hypertrophy or in normotensive subjects. No differences were found in systolic function among the five groups. Both plasma volume and blood volume were decreased in the concentric remodeling group as compared with the other four groups. However, there were no differences in plasma volume or blood volume among the normal left ventricle, eccentric hypertrophy and concentric hypertrophy groups. These data indicate that a small LV chamber in cases of "concentric remodeling" may be related to decreased plasma and blood volumes, but an enlarged LV chamber in cases of "eccentric hypertrophy" is not likely to be related to either plasma or blood volume levels in mild to moderate untreated essential hypertension.