[Show abstract][Hide abstract] ABSTRACT: The sympathetic nervous system (SNS) of the whole body, including cardiac sympathetic nerves, is activated in patients with severe congestive systolic heart failure (CHF). Carvedilol can improve clinical status in such patients. This study aimed to determine how carvedilol acts on the SNS to improve CHF.
Ten subjects (New York Heart Association criteria III) were treated using carvedilol at 2.5 mg/d for 1 week. Before and after treatment, subjects walked on a treadmill for 6 minutes, and plasma concentrations of carvedilol, norepinephrine, and 3,4-dihydroxyphenyl glycol were measured. After treatment, norepinephrine was decreased at rest (3.2 ± 0.3 pmole/mL to 2.1 ± 0.4 pmole/mL, P < 0.05), while standing (5.4 ± 1.2 to 3.3 ± 0.7 pmole/mL, P < 0.01) and during exercise (6.5 ± 1.3 pmole/mL to 5.1 ± 1.1 pmole/mL, P < 0.05). Regression lines for percentage changes in norepinephrine and 3,4-dihydroxyphenyl glycol were compared before and after treatment, showing steeper slopes after treatment (P < 0.05). Plasma carvedilol concentrations (1.8 ± 0.3 ng/mL) did not reach β-adrenoceptor-blocking levels of effect.
Carvedilol is considered to improve function of uptake-1 for the whole-body SNS, including the cardiac SNS, and does not seem to block adrenoceptors at such low doses in CHF patients. However, both effects seem to work at high doses in clinical settings.
No preview · Article · Feb 2012 · Journal of cardiovascular pharmacology
[Show abstract][Hide abstract] ABSTRACT: Hypertension causes proteinuria and is an important factor in the progress of renal dysfunction. Increases in various proteins in urine are caused by malfunction of the glomerulus and the renal tubules. In the present study, the effects of hypertension on urinary excretion levels of various proteins were investigated to show the tubular cell malfunction in hypertensive patients.
The subjects included 55 non-diabetic hypertensive patients without previous treatment and 42 normotensive individuals without microalbuminuria. Total urinary protein/creatinine ratio was measured, and urinary proteins were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE).
Total urinary protein/creatinine ratio was higher in hypertensive patients than in normotensive individuals (122.0+/-11.0 vs. 60.6+/-3.1 mg/gCr; p<0.001). SDS-PAGE resolved 15 protein fractions from the urine of both groups. Thirteen fractions were more intensely stained in samples from the hypertensive than from the normotensive. Two fractions did not differ between the groups. Hypertension increased the urinary excretion of various proteins including proteins of less than 40 kDa, called tubular proteins, in addition to albumin.
Hypertension differently influenced the excretion of each urinary protein fraction. Tubular malfunction should be considered in hypertensive patients in addition to glomerular malfunction.
[Show abstract][Hide abstract] ABSTRACT: The clinical importance of simultaneous analysis of 3,4-dihydroxyphenylglycol with other human plasma catecholamines has been investigated to better understand the sympathetic nervous system. However, previous reports have had analytical difficulties with both resolution and extraction. The current study uses a reversed-phase triacontylsilyl silica (C30) column under the mobile phase condition without ion-pair reagents to separate catecholamines and their metabolites, with above 91% recoveries for intra-assay, above 85% for inter-assay, and less than 10% (n=5) coefficient of variation. Lower detection limits (S/N=4) and quantification limits (S/N=6) were 40 and 100 pg/mL for norepinephrine, 3,4-dihydroxyphenylglycol, and 3,4-dihydroxyphenylalanine, 10 and 20 pg/mL for epinephrine, 10 and 40 pg/mL for dopamine. Linear ranges were from 40 to 5000 pg/mL for norepinephrine and 3,4-dihydroxyphenylalanine, from 100 to 5000 pg/mL for 3,4-dihydroxyphenylglycol, and from 10 to 2000 pg/mL for epinephrine and dopamine. The C30 column may prove clinically useful, as it provides a convenient and simultaneous method of evaluation of human plasma catecholamines.
No preview · Article · Feb 2006 · Journal of Chromatography B
[Show abstract][Hide abstract] ABSTRACT: Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) is frequently used to analyze urinary proteins, but appropriate urine sample preparation is essential, because urinary proteins are present in small concentrations, and urine contains high concentrations of salts and metabolic wastes. The aim of this study was to determine the optimum method for urine sample preparation. The effects on urinary protein recovery of pretreating the ultrafiltration apparatus with various agents (Triton X-100, Tween20, PEG compound, and SDS) were studied; Triton X-100 was found to be the most effective agent. Ultrafiltration and acetone precipitation were compared as sample preparation methods for SDS-PAGE. Recovery of urinary protein using ultrafiltration (89.5 ± 8.1%) was better than that achieved by using acetone precipitation (75.1 ± 12.2%) (p < 0.01). Integrated densitometric values for five protein bands (62, 52, 39, 31, and 6 kDa) were higher for ultrafiltration samples than for acetone samples (42350 ± 2568 vs. 37010 ± 725, 34665 ± 1519 vs. 32355 ± 2278, 10755 ± 1683 vs. 8870 ± 941, 65920 ± 3354 vs. 60680 ± 3651, and 1355 ± 160 vs. 1130 ± 211, respectively) (p < 0.05), although differences for the other nine bands were not significant. In conclusion, ultrafiltration is a suitable method for preparing urine samples for SDS-PAGE.
No preview · Article · Jan 2006 · Journal of health science
[Show abstract][Hide abstract] ABSTRACT: Objective: Hypertension causes various organ damages such as brain, heart and kidney. It is accepted that the urinary albumin excretion
increases along with the severity of renal damage. Kidney excretes not only albumin but also other proteins. The aim of this
study is to examine whether elevation of blood pressure increases urinary proteins excretion.
No preview · Article · May 2005 · American Journal of Hypertension
[Show abstract][Hide abstract] ABSTRACT: High blood pressure after a natural disaster is tentatively considered to be due to elevation of sympathetic nerve activity. A volcano in Japan erupted on March 31, 2000, and people living in the vicinity of the volcano were evacuated to safe shelters. We found that many evacuees developed high blood pressure while staying at evacuation centers. The aim of this study was to investigate why their blood pressures stayed elevated.
Sixty-five evacuees, who were staying evacuation centers for 4 months, were examined for blood pressure, urinary sodium excretion, urinary potassium excretion, and plasma and urinary catecholamines.
Associations were found between systolic blood pressure and sodium excretion (r = 0.311, p < 0.05) and between systolic blood pressure and the ratio of urinary sodium to urinary potassium (r = 0.320, p < 0.05). However, no association was found between blood pressure and plasma and urinary catecholamines (NE, DHPG and MHPG).
High sodium consumption was thought to be an important factor in the elevation of blood pressure of the evacuees after acute phase reactions.
[Show abstract][Hide abstract] ABSTRACT: Coronary vasodilator reserve (CVR) is reduced in patients with left ventricular hypertrophy (LVH). However, it is not clear whether there is any difference between the coronary blood flow increase in LVH caused by hypertension (HTH) and that caused by hypertrophic cardiomyopathy (HCM) when the heart rate increases. In this study, 16 subjects with HTH, 10 subjects with HCM, and 10 subjects with normotension (NT) were investigated. Average peak velocities at rest, at pacing, and at dilatation were measured using a Doppler catheter placed at the left descending coronary artery to calculate coronary blood flow (CBF) and CVR. CVR at rest was identical in the HTH and HCM groups, and in both cases was lower than the resting CVR in NT subjects. There were significant differences in the CVR values at a pacing rate of 120 beats/min among the groups. These values were lowest in HCM, highest in NT, and intermediary in HTH subjects. And the percent increase in CBF in HCM at that pacing rate was higher than that in HTH (p < 0.05) or NT (p < 0.05). There was no difference in the percent increase in CBF at this pacing rate between the HTH and NT groups. The effects of elevated heart rate on the percent increase in CBF were different between the HTH and HCM groups. We conclude that cardiac hypertrophy has qualitatively different effects on coronary circulation depending on whether patients have HTH or HCM.
No preview · Article · Nov 2003 · Hypertension Research