Hypertension Research

Original Articles

Clinical studies

The Relationship between Pulse Wave Velocity and Pulse Pressure in Chinese Patients with Essential Hypertension

Yongbin NI, Hongyu WANG, Dayi HU, Weizhong ZHANG

2003Volume 26Issue 11 Pages 871-874
Published: 2003
Released on J-STAGE: June 16, 2004

DOIhttps://doi.org/10.1291/hypres.26.871

JOURNAL FREE ACCESS

Show abstractHide abstract

Aortic pulse wave velocity (PWV) is a significant and independent predictor of cardiovascular disease in hypertensive subjects and in patients with end-stage renal disease, but there have been few studies on PWV in Chinese patients with essential hypertension. In this cross-sectional study, we investigated 3,156 consecutive patients (mean age: 53.7±11.58 years) of the Hypertension Division of Ruijin Hospital in Shanghai. Together with sphygmomanometric blood pressure measurements, aortic PWV was measured using a validated automatic device. PWV in patients with pulse pressure (PP)≥ 60mmHg was significantly greater than that in patients with PP<60 mmHg (p <0.01). PP and PWV were positively related to age (PP: r =0.396, p =0.001; PWV: r =0.531, p =0.001). After adjustment by age and heart rate, PWV was still closely related to PP (r =0.249, p =0.001). At any given systolic blood pressure (SBP), PWV significantly decreased with the increase of diastolic blood pressure (DBP), whereas at any given DBP there was a significant increase of PWV with the increase of SBP. In conclusion, PWV was the major determinant of PP, and was highest in Chinese patients with isolated systolic hypertension, followed by those with systolic and diastolic hypertension, isolated diastolic hypertension, and normal blood pressure. (Hypertens Res 2003; 26: 871-874)

View full abstract

Download PDF (63K)
Differing Anti-Proteinuric Action of Candesartan and Losartan in Chronic Renal Disease

Hiroto MATSUDA, Koichi HAYASHI, Koichiro HOMMA, Kyoko YOSHIOKA, Takesh ...

2003Volume 26Issue 11 Pages 875-880
Published: 2003
Released on J-STAGE: June 16, 2004

DOIhttps://doi.org/10.1291/hypres.26.875

JOURNAL FREE ACCESS

Show abstractHide abstract

It has becoming clear that angiotensin receptor blockers (ARBs) show varying levels of angiotensin II type 1 (AT1) receptor blocking activity. Although the duration of activity and the efficacy on blood pressure of ARB are reported to vary, depending on the agents used, it has not been examined whether the effects on proteinuria and urinary nitrite/nitrate (NO_x) excretion differ in hypertensive patients with chronic renal disease. In the present study, patients with hypertension (>140 and/or 90 mmHg) and chronic renal disease (proteinuria >0.5 g/day; serum creatinine <265μmol/l or creatinine clearance >30 ml/min/1.72 m²) were randomly assigned to perindopril- (n =15), trandolapril- (n =15), candesartan- (n =17), and losartan-treated groups (n =15), and were followed up for 96 weeks. All agents decreased blood pressure to the same level, and none of them had any effect on creatinine clearance. Candesartan, perindopril, and trandolapril reduced proteinuria markedly (from 3.0±0.6 to 1.8±0.5 g/day, 2.7±0.5 to 1.6±0.4 g/day, and 2.7±0.5 to 1.7±0.4 g/day, respectively) at 12 weeks, and the beneficial effect persisted throughout the study. The effect of losartan, however, diminished over the study period. Whereas perindopril, trandolapril, and candesartan markedly increased urinary NO_x excretion (from 257±23 to 1,011±150 μmol/day, 265±70 to 986±130 μmol/day, and 260±62 to 967±67 μmol/day at 12 weeks, respectively), a relatively blunted increase was observed with losartan (from 309±42 to 596±64μmol/day). In conclusion, renal action of ARB varies, with relatively less proteinuria-sparing, as well as NO_x-enhancing, effects observed with candesartan showing the greatest reduction of proteinuria and greatest enhancement of NO_x. Furthermore, renal nitric oxide may contribute to the renal protective action of these agents when administered to patients with chronic renal disease. (Hypertens Res 2003; 26: 875-880)

View full abstract

Download PDF (57K)
Relationship between Polymorphism of the Angiotensin-Converting Enzyme Gene and the Response to Angiotensin-Converting Enzyme Inhibition in Hypertensive Patients

Huimin YU, Yuqing ZHANG, Guozhang LIU

2003Volume 26Issue 11 Pages 881-886
Published: 2003
Released on J-STAGE: June 16, 2004

DOIhttps://doi.org/10.1291/hypres.26.881

JOURNAL FREE ACCESS

Show abstractHide abstract

The aim of this study was to investigate the relationship between polymorphism of the angiotensin-converting enzyme (ACE) gene and the blood pressure response to ACE inhibition in a hypertensive cohort. Imidapril (5-10 mg/day) or benazepril (10-20 mg/day) was administered for 6 weeks to 517 essential hypertensives. ACE gene polymorphism was examined by the polymerase chain reaction (PCR) method and the patients were classified as having the 190-bp deletion homozygous (DD) genotype, the 490-bp insertion homozygous (II) genotype, or the 490-bp insertion, 190-bp deletion heterozygous (ID) genotype. The achieved change in systolic and diastolic blood pressure (SBP and DBP) was analyzed for association with genotypes at the ACE gene locus. The DD genotype was observed in 132 patients (25.5%), the ID genotype in 255 patients (49.3%), and the II genotype in 130 patients (25.2%). The SBP reductions in the patients with the DD genotype, II genotype, and ID genotype were -14.5±12.7 mmHg, -14.3±13.1 mmHg and -14.0±12.2 mmHg, respectively (p =0.94). The DBP reductions in the patients with the DD genotype, II genotype, and ID genotype were -8.7±7.4 mmHg, -8.7±7.7 mmHg and -8.5±6.7 mmHg, respectively (p =0.96). There was no significant association between the ACE gene polymorphisms and the response to ACE inhibition. These results suggest that ACE genotype does not predict the blood pressure-lowering response to antihypertensive treatment with ACE inhibition. (Hypertens Res 2003; 26: 881-886)

View full abstract

Download PDF (51K)
Plasma Adrenomedullin Is Closely Correlated with Pulse Wave Velocity in Middle-Aged and Elderly Patients

Toshihiro KITA, Kazuo KITAMURA, Seiichi HASHIDA, Kazuhiro MORISHITA, T ...

2003Volume 26Issue 11 Pages 887-893
Published: 2003
Released on J-STAGE: June 16, 2004

DOIhttps://doi.org/10.1291/hypres.26.887

JOURNAL FREE ACCESS

Show abstractHide abstract

Arterial stiffness as measured by pulse wave velocity (PWV) is a major predictor of cardiovascular disease. Adrenomedullin (AM), a hypotensive peptide, works as a compensatory factor for arterial sclerosis. The aim of this study was to investigate the relationship between PWV and the plasma concentration of AM in risk-loading patients. One hundred and twenty-six inpatients aged 30 to 75 years with or without varying degrees of atherosclerosis were investigated. Patients with heart and/or renal failure were excluded. The PWV was measured using an automatic waveform analyzer, and the plasma AM level was measured using a newly developed, hypersensitive immunoenzymometric assay system. The PWV increased with the increasing number of cardiovascular risk factors and organ damage in the patients. A positive correlation between the PWV and AM level was observed (r =0.375, p <0.0001, n =126). Seventy-four patients were receiving antihypertensive medications; medication did not affect the correlation. Multivariate regression analysis revealed that the PWV was significantly and independently associated with age, systolic blood pressure, and AM level. These results indicate that the plasma AM concentration could serve as a marker of advanced arterial sclerosis as estimated by increased PWV. (Hypertens Res 2003; 26: 887-893)

View full abstract

Download PDF (44K)
Serum Cystatin C Level Is a Marker of End-Organ Damage in Patients with Essential Hypertension

Sanae WATANABE, Takafumi OKURA, Jun LIU, Ken-ichi MIYOSHI, Tomikazu FU ...

2003Volume 26Issue 11 Pages 895-899
Published: 2003
Released on J-STAGE: June 16, 2004

DOIhttps://doi.org/10.1291/hypres.26.895

JOURNAL FREE ACCESS

Show abstractHide abstract

High urinary albumin excretion rate (AER) has been associated with the presence of atherosclerotic vascular damages and is an independent risk factor for all causes of death and cardiovascular morbidity and mortality in essential hypertensive patients. Serum cystatin C (s-CC) is a recently identified nonglycosylated 13-kD basic protein that has been suggested to be a useful marker of glomerular filtration rate. In the present study, we investigated the relationship between s-CC level and end-organ damages in the kidney, heart, and vessels of patients with essential hypertension. Sixty patients with essential hypertension participated in the present study. Patients with renal failure were excluded. Serum-CC level was measured by a particle-enhanced turbidimetric assay. Left ventricular mass index (LVMI) and intima media thickness (IMT) in the common carotid arteries were evaluated by ultrasound images. Twenty-four-hour blood pressure was measured by a cuff-oscillometric method. Serum-CC level was negatively correlated with creatinine clearance (r = -0.617, p <0.0001). It was also correlated with mean 24-h systolic blood pressure (24h-SBP) (r =0.308, p =0.0167), LVMI (r =0.528, p <0.0001), and IMT (r =0.539, p <0.0001). Both AER and s-CC level were independently associated with mean 24h-SBP. AER but not s-CC level was associated with HDL-cholesterol. The present study was the first to demonstrate that s-CC level is a useful and convenient parameter of renal function, and may also prove to be an early marker of the severity of end-organ damage in patients with essential hypertension. (Hypertens Res 2003; 26: 895-899)

View full abstract

Download PDF (48K)

Experimental studies

Effect of Amlodipine and Cilazapril Treatment on Platelet Ca²⁺ Handling in Spontaneously Hypertensive Rats

Tetsuya OSHIMA, Norihisa ONO, Ryoji OZONO, Yukihito HIGASHI, Mari ISHI ...

2003Volume 26Issue 11 Pages 901-906
Published: 2003
Released on J-STAGE: June 16, 2004

DOIhttps://doi.org/10.1291/hypres.26.901

JOURNAL FREE ACCESS

Show abstractHide abstract

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 amlodipine (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 ionomycin-stimulation 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. (Hypertens Res 2003; 26: 901-906)

View full abstract

Download PDF (49K)
Effects of Exercise Training on Glomerular Structure in Fructose-Fed Spontaneously Hypertensive Rats

Kazunori YOSHIDA, Takayuki KAWAMURA, Hong-Lan XU, Lina JI, Nobuyoshi M ...

2003Volume 26Issue 11 Pages 907-914
Published: 2003
Released on J-STAGE: June 16, 2004

DOIhttps://doi.org/10.1291/hypres.26.907

JOURNAL FREE ACCESS

Show abstractHide abstract

A high-fructose diet (HFD) has been shown to elevate blood pressure (BP) and to decrease insulin sensitivity in rats. Although running exercise can attenuate these phenomena, its effect on target organ protection is not clear. We investigated whether exercise training has renal protective effects in this model. Nine-week-old spontaneously hypertensive rats were allocated to groups that received HFD or a control diet (control group) for 15 weeks. At the age of 10 weeks, fructose-fed rats were allocated to groups that were given vehicle (FRU group), temocapril, an angiotensin converting enzyme inhibitor (TEM group), exercise training (EX group; treadmill running), or temocapril plus exercise training (TEM+EX group). BP was higher in the FRU group than in the control group. Exercise training tended to decrease BP and temocapril treatment decreased BP significantly. Proteinuria was similar in the five groups. Plasma leptin concentration and epididymal fat weight were lower in the EX and TEM+EX groups than in the FRU group. In the soleus muscle of the FRU group, the composite ratio of type I fiber was decreased and that of type IIa fiber was increased compared with those in the control group. Both temocapril and exercise training restored these ratios. The glomerular sclerosis index (GSI) was higher in the FRU group than in the control group. GSI was decreased equally in the TEM, EX, and TEM+EX groups and was positively correlated with plasma leptin concentration. The results suggest that exercise training ameliorates glomerular sclerosis through mechanisms other than a reduction in BP. (Hypertens Res 2003; 26: 907-914)

View full abstract

Download PDF (84K)
Angiotensin II Type 2 Receptor Inhibits Prorenin Processing in Juxtaglomerular Cells

Atsuhiro ICHIHARA, Matsuhiko HAYASHI, Nobuhisa HIROTA, Hirokazu OKADA, ...

2003Volume 26Issue 11 Pages 915-921
Published: 2003
Released on J-STAGE: June 16, 2004

DOIhttps://doi.org/10.1291/hypres.26.915

JOURNAL FREE ACCESS

Show abstractHide abstract

Long-term treatment with an angiotensin II type 1 receptor blocker (ARB) has been shown to decrease the plasma renin activity (PRA) of hypertensive patients, whereas PRA remains elevated during angiotensin-converting enzyme inhibitor (ACEI) treatment. In the present study, we used rat juxtaglomerular (JG) cells to elucidate the mechanism(s) involved in the differential regulation of PRA between ARB and ACEI treatment. Addition of 100 nmol/l angiotensinogen (Aogen) to JG cells (n =6 primary cultures) significantly increased the medium angiotensin (Ang) II levels from 14±2 to 440±9 pg/ml and suppressed the renin secretion rate (RSR) from 39.6±5.4% to 6.3±1.8% without affecting active renin content (ARC) or total renin content (TRC). In the Aogen-treated cells, the ACEI, delapril hydrochloride (CV3317, 10μmol/l), significantly decreased the medium Ang II levels to 58±14 pg/ml and increased RSR to 39.8±4.1% without affecting ARC or TRC. The ARB, an active metabolite of candesartan cilexetil (CV11974, 10μmol/l), however, significantly increased the medium Ang II levels and RSR to 486±15 pg/ml and 40.9±9.8%, respectively, and decreased ARC from 63.2±6.8 to 21.6±3.6 ng of Ang I•h^-1•million cells^-1 without affecting TRC. The decreases in ARC of the Aogen+CV11974-treated cells (n =6 primary cultures) were inhibited by an Ang II type 2 receptor blocker, PD123319 (10μmol/l). JG cells (n =6 primary cultures) were also treated with an Ang II type 2 receptor agonist, CGP42212A (0.1μmol/l). CGP42212A significantly increased RSR from 38.2±1.6% to 49.7±4.7% and decreased ARC from 60.8±3.0 to 25.3±2.8 ng of Ang I•h^-1•million cells^-1 without affecting TRC. Addition of CV11974 did not alter the RSR, ARC, or TRC of the CGP42212A-treated cells; however, PD123319 abolished the effects of CGP42212A. These results indicate that, distinct from ACEIs, ARBs inhibit prorenin processing of JG cells through Ang II type 2 receptors. Long-term treatment with an ARB may decrease PRA in part by diminishing the storage of active renin in JG cells. (Hypertens Res 2003; 26: 915-921)

View full abstract

Download PDF (63K)
Reduced Membrane-Bound Catechol-O-Methyltransferase in the Liver of Spontaneously Hypertensive Rats

Makoto TSUNODA, Jukka TENHUNEN, Carola TILGMANN, Hiroyuki ARAI, Kazuhi ...

2003Volume 26Issue 11 Pages 923-927
Published: 2003
Released on J-STAGE: June 16, 2004

DOIhttps://doi.org/10.1291/hypres.26.923

JOURNAL FREE ACCESS

Show abstractHide abstract

We have previously reported that methylation of catecholamines by catechol-O-methyltransferase (COMT) was attenuated in spontaneously hypertensive rats (SHR) with acute hypotension as compared with that of Wistar-Kyoto (WKY) rats. Here we examined the soluble (S-) and membrane-bound (MB-) COMT activities and COMT protein in the liver, kidney, and erythrocytes in both strains. Both the activities and the amounts of MB-COMT in the liver were lower in SHR than in WKY rats, but no such trend was found in the kidney or erythrocytes. Nor was such a trend observed in any of these three tissues for S-COMT. These results indicate that liver MB-COMT may be a relevant factor in blood pressure regulation in rats. (Hypertens Res 2003; 26: 923-927)

View full abstract

Download PDF (31K)
Regulation of Cytochrome P-450 4A Activity by Peroxisome Proliferator-Activated Receptors in the Rat Kidney

Tsuneo ISHIZUKA, Osamu ITO, Liping TAN, Susumu OGAWA, Masahiro KOHZUKI ...

2003Volume 26Issue 11 Pages 929-936
Published: 2003
Released on J-STAGE: June 16, 2004

DOIhttps://doi.org/10.1291/hypres.26.929

JOURNAL FREE ACCESS

Show abstractHide abstract

The localization of cytochrome P-450 4A, peroxisome proliferator-activated receptor (PPAR)α, and PPARγ proteins, and the inducibility of P-450 4A expression and activity by PPAR agonists were determined in the rat kidney. The expressions of these proteins in isolated nephron segments were evaluated by immunoblot analysis, and the production of 20-hydroxyeicosatetraenoic acid (20-HETE) was measured as P-450 4A activity. P-450 4A proteins were expressed predominantly in the proximal tubule (PT), with lower expression in the preglomerular arteriole (Art), glomerulus (Glm), and medullary thick ascending limb (mTAL), but their expression was not detected in the inner medullary collecting duct (IMCD). PPARα protein was expressed in the PT and mTAL, and PPARγ protein was expressed in the IMCD and mTAL. Treatment with clofibrate, the PPARα agonist, increased P-450 4A protein levels and the production of 20-HETE in microsomes prepared from the renal cortex, whereas treatment with pioglitazone, the PPARγ agonist, affected neither of them. These results indicate that PPARα and PPARγ proteins are localized in different nephron segments and the inducibility of P-450 4A expression and activity by the PPAR agonists correlates with the nephron-specific localization of the respective PPAR isoforms. (Hypertens Res 2003; 26: 929-936)

View full abstract

Download PDF (73K)

Register with J-STAGE for free!