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Effect of simvastatin on endothelial function in cardiac syndrome X patients.

Patients with cardiac syndrome X with mild hypercholesterolemia were randomized to placebo (n = 20) or simvastatin 20 mg/day (n = 20). In the simvastatin group, there was a significant (26%; p < 0.0001) decrease in total cholesterol, a 38% (p < 0.0001) decrease in low-density lipoprotein cholesterol levels, and 7% a (p < 0.0001) increase in high-density lipoprotein cholesterol levels, without significant changes in triglyceride levels. Brachial artery flow-mediated dilation increased significantly (52% relative increase, p < 0.0001), and the time to > 1-mm ST-segment depression during stress testing was longer by the end of the study (p < 0.0001).

Aged↗

Effect of hypoxia-reoxygenation on endothelial function in porcine cardiac microveins.

BACKGROUND: The cardiac venous system possesses up to 30% of total coronary vascular resistance and the effect of hypoxia-reoxygenation (H-R) and St Thomas (ST) cardioplegic solution on the vein is unknown. We investigated the effects of H-R, with or without ST, on endothelium-derived hyperpolarizing factor (EDHF)-mediated relaxation in porcine cardiac microveins under clinically relevant temperatures. METHODS: The microveins (diameter 200 to 450 microM) mounted in a myograph were subjected to hypoxia (Po2 < 5 mm Hg) for 30 minutes in Krebs solution (n = 8) or for 60 minutes in Krebs (n = 8) or in ST at 37 degrees C (n = 8) or 4 degrees C (n = 8), followed by 30-minute reoxygenation. The microvein was precontracted with thromboxane A2 mimetic U46619 (-7 log M) and the EDHF-mediated relaxation was induced by bradykinin (-10 to -6 log M) in the presence of indomethacin, NG-nitro-L-arginine, and oxyhemoglobin before and after H-R. RESULTS: The maximal EDHF-mediated relaxation was significantly reduced after 30-minute hypoxia (38.7 +/- 2.0% vs 61.1 +/- 2.3%, n = 8, p < 0.001) or 60-minute hypoxia in either Krebs or ST at 37 degrees C (Krebs: 27.8 +/- 1.2% vs 56.6 +/- 2.5%, n = 8, p < 0.001; ST: 23.8 +/- 4.1% vs 57.1 +/- 1.5%, n = 8, p < 0.001). The relaxation was significantly less after prolonged H-R in Krebs (p < 0.001). Incubation in Krebs or ST at 4 degrees C also reduced the EDHF-mediated relaxation (Krebs: 25.3 +/- 3.3%, n = 8, p < 0.001; ST: 29.1 +/- 4.4%, n = 8, p < 0.001) and there were no significant differences between Krebs and ST regarding the relaxation at either 37 degrees C or 4 degrees C (p > 0.05). CONCLUSIONS: We conclude that (1) H-R impairs EDHF-mediated relaxation in the coronary microveins with more severe injury during prolonged H-R and (2) ST does not provide protection to the EDHF-mediated relaxation impaired by H-R at either 37 degrees C or 4 degrees C.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

Comparison of endothelial function in the carotid artery between normal and short-term hypercholesterolemic rabbits.

The present study was undertaken to investigate and compare the vascular function in carotid arteries isolated from normal short-term hypercholesterolemic rabbits. Rabbits were fed normal or 0.5% cholesterol chow for 5 weeks. The tension of isolated carotid artery rings was measured isometrically. Serum lipid levels were measured and morphometric analysis was performed. And content of nitrate/nitrite in the carotid artery was also determined. In the carotid artery precontracted by phenylephrine, the cholesterol chow diet administered for 5 weeks decreased acetylcholine-induced relaxation at only middle concentrations, though it significantly increased the content of nitrate/nitrite, the sum of stable nitric oxide metabolites, in the carotid artery. Cholesterol chow for 5 weeks had no influence on sodium nitroprusside-induced relaxation in the carotid artery. The N(G)-nitro-L-arginine- and indomethacin-resistant endothelium-dependent relaxation induced by acetylcholine was significantly decreased in rabbits receiving the cholesterol chow as compared to rabbits receiving the control diet. The resistant part of acetylcholine-induced relaxation was significantly inhibited when the carotid artery was treated with glibenclamide, a selective inhibitor of ATP-sensitive K(+) channels, 4-aminopyridine, an inhibitor of voltage-dependent K(+) channels, or charybdotoxin, an inhibitor of large and intermediate conductance Ca(2+)-activated K(+) channels, and it was significantly inhibited by tetraethylammonium, a non-selective inhibitor of Ca(2+)-activated K(+) channels and N,N-di-ethylaminoethyl-2,2-diphenylvalerate hydrochloride (SKF 525a), a nonselective cytochrome P-450 monooxygenase (CYP) inhibitor, or ketoconazole, a selective CYP3A inhibitor in only normal rabbits. These results suggest that short-term hypercholesterolemia decreased EDHF-induced relaxation mediated through K(+) channels in rabbit carotid artery and that it may be due partially to the inhibition of CYP3A system in the carotid artery at an early stage of hypercholesterolemia.

Acetylcholine↗

Short- and long-term influence of diet and simvastatin on brachial artery endothelial function.

BACKGROUND: Endothelium-dependent dilation (EDD) has often been studied in patients with hypercholesterolemia without overt coronary atherosclerosis where an improvement after statin treatment has been documented within few weeks. The aim of the study was to assess the short-term effect of diet as well as short- and long-term effect of simvastatin on EDD in patients with hypercholesterolemia and ischemic heart disease. METHODS: In 43 male patients with hypercholesterolemia and ischemic heart disease, EDD of the brachial artery was measured at baseline, after 3 months on a lipid-lowering diet, and after another 1, 3 and 12 months on simvastatin at 40 mg/day. RESULTS: Three months changes in EDD were neither influenced by diet nor short-term simvastatin therapy (4.9% vs. 4.9% vs. 4.8%, p=ns). Twelve months simvastatin treatment, however, significantly improved EDD by 32.7% (4.9% vs. 6.5%, p=0.007). By regression analysis an individual adjusted increase in EDD during the simvastatin treatment period was seen (coefficient 0.132 a month, p=0.002). A significant reduction in total cholesterol of 31.0% (6.1+/-0.8 vs. 4.2+/-0.7, p<0.001) and LDL cholesterol of 42.6% (4.0+/-0.8 vs. 2.2+/-0.6, p<0.001) was observed. CONCLUSION: EDD is improved after long-term simvastatin therapy; however, neither did 3 months diet or 3 months simvastatin therapy has influence on the EDD.

Aged↗

Prognostic value of brachial artery endothelial function and wall thickness.

OBJECTIVES: We sought to examine the prognostic value of brachial artery (BA) flow-mediated vasodilation (FMD) and intima-media thickness (IMT) in patients admitted for invasive evaluation of chest pain. BACKGROUND: Both FMD and IMT of the BA have been associated with coronary risk factors and the presence of coronary artery disease (CAD). Recent studies on the prognostic value of FMD have been conflicting. METHODS: In 398 consecutive patients (age 54 +/- 9 years) undergoing coronary angiography, FMD and IMT of the BA were measured using high-resolution ultrasound (13 MHz). Patients were divided into two groups according to the FMD median (7.6%). After a mean follow-up of 39 +/- 12 months, cardiovascular events were documented. RESULTS: No difference was found in the number of cardiovascular events between groups. On multivariate Cox regression analysis, including age, number of risk factors, BA diameter, presence of CAD, FMD, and IMT, only the presence of CAD and IMT remained significantly associated with cardiovascular events. CONCLUSIONS: Intima-media thickness predicted late (up to 4 years) cardiovascular events in a large population admitted for evaluation of chest pain. In contrast, the long-term prognostic value of a single baseline measure of BA-FMD seems to be limited.

Adult↗

Pycnogenol, French maritime pine bark extract, improves endothelial function of hypertensive patients.

A placebo-controlled, double-blind, parallel group study was performed with 58 patients to investigate effects of French maritime pine bark extract, Pycnogenol, on patients with hypertension. Supplementation of the patients with 100 mg Pycnogenol over a period of 12 weeks helped to reduce the dose of the calcium antagonist nifedipine in a statistically significant manner. The intake of Pycnogenol decreased endothelin-1 concentrations significantly compared to placebo while concentrations of 6-keto prostaglandin F1a in plasma were significantly higher compared to placebo. Values for nitric oxide (NO) in plasma increased in both groups, but the differences were not significant. Angiotensin II concentrations in plasma were lowered in the placebo group to a larger extent than in the Pycnogenol group. Heart rate, electrolytes and blood urea nitrogen were not changed during treatment in both groups of patients. Unwanted effects observed in both groups were of mild and transient nature, such as gastrointestinal problems, vertigo, headache and nausea. Differences in rate of side effects were not statistically significant between the two groups. Study results support a supplementation with Pycnogenol for mildly hypertensive patients.

6-Ketoprostaglandin F1 alpha↗