Cardiovascular complications are a major cause of morbidity and mortality in patients with renal failure. Death due to myocardial infarction and to stroke is more frequent in hemodialysis patients than in the total population. These cardiovascular diseases are mainly the consequence of atherosclerosis and cause decreased life expectancy in patients with renal failure. Ultrasound techniques now make it possible to measure atherosclerotic lesions in big and medium-sized arteries. Thickening of the intima-media-complex is an early sign of atherosclerosis in these vessels. It reduces the distensibility of the arteries during systole. The distensibility of big and medium-sized arteries can be determined using ultrasound-doppler-techniques. In our studies, the intima-media-thickness of the carotid artery was significantly (p<0.01) increased in patients with chronic renal failure (1.32±0.49mm, n=28) as compared with aged-matched healthy control subjects (0.75±0.20, n=29). The distensibility coefficient was higher (p<0.05) in healthy controls (26±1.8 10^-3/kPa, n=12) than in patients with renal insufficiency (19±1.7 10^-3/kPa, n=12). This demonstrates increased stiffness of the vessel wall resulting in loss of Windkessel function and increased work load of the heart. (Hypertens Res 2000; 23: 3-6)

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Recently, there have been some reports indicating that calcium antagonists induce a reflex increase in sympathetic activity, triggering cardiac events, especially in coronary artery disease (CAD) patients. In this study, we assessed heart rate (HR) variability (HRV) using power spectral analysis of the 24-h RR interval in 25 hypertensive outpatients with CAD treated with nifedipine. We compared blood pressure (BP), HR, and HRV variation in the same patients substituting benidipine (long-acting) for nifedipine (intermediateacting). There were no significant differences in 24-h, daytime, nighttime, and morning BP between the nifedipine phase and the benidipine phase. HRV parameters (LF: low frequency power, HF: high frequency power, LF/HF ratio) also showed no significant differences in 24-h, daytime, nighttime, and morning LF, HF, and LF/HF ratio between the nifedipine phase and the benidipine phase. Blood pressure, HR, and HRV parameters, except the LF component from 2 to 4h after nifedipine administration (the most effective duration), showed no differences compared to before administration. The LF component after the nifedipine administration was lower than before administration. In conclusion, in hypertensive patients with CAD, whose BP levels were well-controlled by twice-daily use of intermediate-acting nifedipine, switching from nifedipine to a long-acting calcium antagonist, benidipine, maintained well-controlled BP levels to a similar degree, but it may not have additional benefit in sympatho-vagal balance. (Hypertens Res 2000; 23: 7-14)

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We sought a noninvasive alternative method of monitoring peripheral vascular resistance continuously in humans, based on the analysis of arterial pressure waveforms. Radial arterial pressure waveforms were recorded noninvasively with a tonometer and analysed using a neural network method. To test the accuracy of this method, the peripheral vascular resistance was also determined by an invasive thermodilution method using a Swan-Ganz catheter in 20 subjects. To test the method in a clinical application, peripheral vascular resistance was determined by the noninvasive method before and after administration of nifedipine in 6 patients with essential hypertension. Neural network analysis of waveforms reliably yielded values between 0.00 and 1.00. Peripheral vascular resistance determined by neural network analysis and according to the invasive method showed a significant (p<0.005) positive linear correlation. The peripheral vascular resistance measured by neural network analysis showed a significant (p<0.05) decrease 30 min after administration of nifedipine, paralleling a decrease in blood pressure. Neural network analysis of tonometric radial artery waveforms provides an accurate, noninvasive, and continuous index of peripheral vascular resistance in human subjects. This simple method should permit more extensive homodynamic studies and larger epidemiological surveys in contrast to those undertaken using invasive techniques. (Hypertens Res 2000; 23: 15-19)

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This study examined the relationship of home blood pressure measurement to medication compliance and name recognition of antihypertensive drugs in outpatients with hypertension. A total of 1, 452 consecutive outpatients (842 males, 610 females; mean age 65±11 yr) seeking care at our institute answered questions at our cardiovascular outpatient clinic such as whether they had a sphygmomanometer at home, how often they measured their blood pressure at home, and how often they missed taking their medication. Among a total of 777 patients on antihypertensive drugs who had a sphygmomanometer at home, 16 of the 242 patients (6.5%) who measured their home blood pressure every day occasionally missed taking their medication, whereas this number was 22 for the 216 patients (10.1%) who measured their home blood pressure several times a week, 16 for the 146 patients (11.0%) who measured their home blood pressure several times a month, and 25 for the 173 patients (14.5%) who never measured their home blood pressure (p<0.01 between patients who measured their home blood pressure every day and those who did not measure their home blood pressure). Among a total of 271 patients taking one or two antihypertensive drugs, the number of patients who could name their antihypertensive drugs was 47 of the 86 patients (55%) who measured their home blood pressure every day, 43 of the 78 patients (55%) who measured their home blood pressure several times a week, 24 of the 41 patients (58%) who measured their home blood pressure several times a month, and 22 of the 66 patients (33%) who never measured their home blood pressure (p<0.02). In conclusion, medication compliance and antihypertensive drug name recognition were better in patients who measured their home blood pressure than in patients who did not measure their home blood pressure. From these results, we conclude that physicians should recommend home blood pressure measurement to patients being treated with antihypertensive drugs, because there is a possibility that home blood pressure measurement might improve medication compliance. (Hyperfens Res 2000; 23: 21-24)

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There is increasing evidence of important cardiovascular effects of aldosterone via classical mineralocorticoid receptors in the heart. Aldosterone plus excess salt administration has been shown to produce both cardiac hypertrophy and cardiac fibrosis in rats. Various clinical studies have reported that aldosterone plays an important role in cardiac hypertrophy; however, the factors that control plasma aldosterone concentrations during angiotensin-convening enzyme (ACE) inhibitor treatment have still not been established. In the present study, we examined the relationship between plasma aldosterone concentrations and the degree of ACE inhibition in 25 essential hypertensive patients treated with an ACE inhibitor. Blood pressure decreased with treatment and plasma ACE activity, estimated in vitro (by a colorimetric method) and in vivo (by plasma angiotensin II/angiotensin I ratio) assay, was suppressed compared with that of hypertensive patients treated with medication other than ACE inhibitors. No relationship was found between the level of ACE inhibition and plasma aldosterone concentrations, which rose in parallel with the duration of ACE inhibitor treatment. The present study demonstrates that continuous ACE inhibitor therapy produces significant suppression of plasma ACE activity in essential hypertensive patients, but that no relationship exists between plasma aldosterone concentrations and levels of ACE inhibition. Plasma aldosterone concentrations tend to increase with the duration of ACE inhibitor treatment, although this increase did not reflect a reduced inhibition of ACE activity. (Hypertens Res 2000; 23: 25-31)

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We investigated the effect of long-term treatment with a calcium antagonist (nicardipine hydrochloride retard tablet) and a diuretic (trichlormethiazide) on quality of life (QOL) in elderly hypertensives in a multicenter, randomized, double-blind, comparative study (National Intervention Cooperative Study in Elderly Hypertensives Study Group). The percentage of patients who experienced side effects was 17.2% in the nicardipine group and 18.1% in the trichlormethiazide group and 2.9% and 4.3% of participants, respectively, withdrew due to those side effects. These results suggested that nicardipine was tolerated slightly better than trichlormethiazide. There were no significant differences between the two groups in terms of total QOL score or in degree of change (Δ score) before and after calcium antagonist or diuretic administration. Lower score was seen in 3 categories (general symptoms, sleep scale, and sexual function) in the trichlormethiazide group (p<0.05) and in one category (cognitive function) in the nicardipine group, but there was no significant difference in Δ score in any of the individual items. In conclusion, the two antihypertensive agents had nearly equivalent effects on QOL in the long-term treatment of hypertension in the elderly and that neither resulted in a deterioration in QOL. (Hypertens Res 2000; 23: 33-37)

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Interest in mitochondrial calcium (Ca²⁺) uptake and release waned as it became apparent that sarcoplasmic reticulum calcium stores dominate the control of cytoplasmic calcium concentration. Our recent demonstration of a very large rise in vascular smooth muscle (VSM) cytoplasmic sodium (Na⁺) concentration after inhibition of the sodium, potassium-ATPase (sodium pump) led us to several questions. Do VSM mitochondria show Na⁺ -dependent Ca²⁺ release? Are the documented changes in cytoplasmic Na⁺ concentration sufficient to cause Ca²⁺ release? Do features of the cardiac mitochondrial exchange system, including differential sensitivity to a number of calcium antagonists and cation specificity, apply to VSM? We isolated mitochondria from bovine aorta and mesenteric arteries and employed arsenazo III as the Ca²⁺ indicator. Mitochondria from arterial vessels accumulated added calcium (up to 50nmol Ca²⁺/mg protein) and released Ca²⁺ on exposure to Na⁺. This concentration-dependent relationship was linear from 0 to 10mM of Na⁺, and it plateaued between 20mM and 40mM of Na⁺. VSM mitochondria exposed to 20mM Na⁺ released 118±25nmol Ca²⁺ per mg mitochondrial protein in 20min, when a new equilibrium was reached. Lithium (Li⁺), in contrast to Na⁺, produced much smaller amounts of Ca²⁺ release from the VSM mitochondria. Na⁺ -dependent Ca²⁺ release was antagonized in a concentration-dependent manner by diltiazem (0-320μM) with a Ki of 10.2μM. Nifedipine had a lesser effect, and verapamil produced almost no inhibition. VSM mitochondria responses resemble those from heart mitochondria in that Na⁺ -dependent Ca²⁺ release is present with a similar range of sensitivity to Na⁺ and a similar pattern of influence of diltiazem, nifedipine and verapamil. However, the influence of Li⁺ on Ca²⁺ release was much smaller and the amount of the Ca²⁺ released was much greater for VSM mitochondria compared with that reported for heart mitochondria. The large amount of Ca²⁺ released and the range of Na⁺ concentration that provoked Ca²⁺ release being within the physiologically achievable range raise the interesting possibility that these mechanisms may modify intramitochondrial cytosolic Ca²⁺ concentration, and hence could potentially contribute to the contractile response that follows inhibition of the sodium pump. (Hypertens Res 2000; 23: 39-45)

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We previously reported that several markers on rat chromosome (Chr) 4 cosegregated with the occurrence of cerebral stroke and brain edema in stroke-prone spontaneously hypertensive rats (SHRSP). To obtain insights into the positional candidate genes for stroke susceptibility in this region, we mapped four genes, Taurine transporter (Tau), tumor necrosis factor receptor (Tnfr), GABA transporter (Gat1) and glucose transporter-3 (Glut3) genes, using newly developed simple sequence repeat (SSR) markers on rat Chr 4. We isolated the SSRs for the genes either by screening a rat genomic library or by searching the GenBank database. By linkage analysis using two sets of backcrosses, Gat1 and Tnfr were mapped in the region associated with stroke, while Taut was located distant from the region. The Glut3 locus was also assigned to rat Chr 4 using a rat x mouse hybrid clone panel. These results indicated that the Tnfr, Gat1 and Glut3 genes were good positional candidates for the stroke susceptibility in SHRSP, suggesting that further evaluation of these genes by functional studies could prove useful. (Hypertens Res 2000; 23: 47-50)

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