No abstract

The dehydroepiandrosterone (DHEA) concentration decreases with age. There is evidence that DHEA has a protective effect against age-related disorders, including cardiovascular disease. Accordingly, we examined the effect of DHEA supplementation (25 mg/d) on endothelial function, insulin sensitivity, and fibrinolytic activity in 24 men with hypercholesterolemia (mean age, 54 +/- 1 yr). All subjects were enrolled in a randomized, double-blind study. Flow-mediated dilation of brachial artery after transient occlusion, which was expressed as the percent change from the baseline value of the diameter, increased significantly with DHEA supplementation [DHEA: baseline, 3.9 +/- 0.5%; 4 wk, 6.9 +/- 0.7%; 8 wk, 7.9 +/- 0.6%; 12 wk, 8.4 +/- 0.7% (P < 0.01 vs. baseline for all, by ANOVA); placebo: 4.1 +/- 0.6%, 4.5 +/- 0.5%, 3.9 +/- 0.5%, and 4.4 +/- 0.6% (P < 0.01 for all, by ANOVA)]. There was a significant concurrent reduction in the plasma levels of plasminogen activator inhibitor type 1 during DHEA supplementation [DHEA: 9.1 +/- 2.2, 6.4 +/- 2.3, 5.5 +/- 2.8, and 5.1 +/- 2.0 IU/ml (P < 0.01 vs. baseline, by ANOVA); placebo: 9.0 +/- 2.1, 10.4 +/- 2.2, 9.5 +/- 2.2, and 9.6 +/- 2.1 IU/ml (P < 0.01, by ANOVA)]. DHEA supplementation also decreased steady state plasma glucose [DHEA: baseline, 178.9 +/- 12.2; 12 wk, 132.0 +/- 12.8 mg/dl (P < 0.01, by ANOVA); placebo: 181.0 +/- 13.8 and 179.6 +/- 12.4 mg/dl (P < 0.01, by ANOVA)]. In contrast, steady state plasma insulin did not change during the study in either group. The low dose DHEA supplementation improves vascular endothelial function and insulin sensitivity and decreases the plasminogen activator inhibitor type 1 concentration. These beneficial changes have the potential to attenuate the development of age-related disorders such as cardiovascular disease.

No abstract

This study demonstrated that administration of enalapril reduces the increased procoagulant activity in patients with myocardial infarction associated with inhibition of the activation and accumulation of macrophages and monocytes.

We examined the alteration of platelet aggregability in acute hyperglycemia during 75-gram oral glucose tolerance tests (OGTT). Twenty subjects underwent 75-gram OGTT and venous blood samples were obtained before (0 min), 60, 120 and 180 min postload. Platelet aggregability shown as the number of small platelet aggregates was measured with a novel laser-light scattering (LS) method. Platelet aggregability increased in parallel with both glucose and immunoreactive insulin (IRI) levels. The number of mean small aggregates at 60 min (12.30 ± 1.10 ϫ 10 4 ) was significantly higher than the one at 0 min (8.32 ± 0.88 ϫ 10 4 , p Ͻ0.001), 120 min (10.63 ± 0.98 ϫ 10 4 , p Ͻ0.05) and 180 min (8.28 ± 0.84 ϫ 10 4 , p Ͻ0.001) (mean ± SEM). Small aggregates correlated positively with plasma glucose levels at 60 min postload (r = 0.67, p = 0.001) while not with IRI. It might be important to suppress transient hyperglycemia for preventing the onset of acute coronary syndromes that could be closely related to platelet hyperaggregability.

These results indicate that urinary biopyrrins levels are increased in patients with HF and are elevated in proportion to its severity.

No abstract

Background-Nitrates are widely used to treat coronary artery disease, but their therapeutic value is compromised by the rapid development of tolerance. Recently, the renin-angiotensin system has been suggested to play an important role in the development of nitrate tolerance. Methods and Results-Sixty-four patients with coronary spastic angina were investigated to clarify the effect of angiotensin II type 1 receptor blocker (ARB) therapy on nitrate tolerance. Transdermal nitroglycerin (10 mg/d) and an ARB (candesartan, 8 mg/d) were administered to 21 patients (GTNϩARB group) for 3 days, whereas transdermal nitroglycerin and placebo were administered to 19 patients (GTN group). Another 18 patients were treated with placebo skin patches and placebo tablets for 3 days (control group). The brachial artery response to incremental doses of intravenous nitroglycerin (0.01, 0.1, and 1.0 g/kg) was measured by ultrasound before and after transdermal nitroglycerin therapy. Before treatment, the arterial diameter was increased by nitroglycerin injection in each group. After treatment, the increase of arterial diameter was significantly suppressed in the GTN group but not in the control or GTNϩARB groups. The plasma level of thioredoxin (a marker of oxidative stress) was increased in the GTN group after treatment (PϽ0.01) but not in the control or GTNϩARB groups. Conclusions-An ARB suppressed the development of nitrate tolerance during transdermal nitroglycerin therapy. These results suggest that increased oxidative stress induced by activation of angiotensin II may play an important role in the development of nitrate tolerance.