PubMed · 6142432
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L C Sellin. 1984. Botulism--an update.. https://pubmed.ncbi.nlm.nih.gov/6142432/
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Patients with hypercholesterolemia have impaired endothelium-dependent vasodilation due to decreased nitric oxide activity. The present study aimed to determine whether this form of endothelial dysfunction is related to enhanced extracellular breakdown of nitric oxide by superoxide anions. To this end, the vascular responses to acetylcholine (an endothelium-dependent vasodilator) and sodium nitroprusside (a direct smooth muscle dilator) were studied before and after combined administration of copper-zinc superoxide dismutase (a scavenger of superoxide anions with poor intracellular penetrance; 6,000 U/min) in 20 normal controls (11 men and 9 women, age 50 +/- 6 years) and in 20 hypercholesterolemic patients (10 men and 10 women, age 49 +/- 9 years). Drugs were infused into the brachial artery and the response of the forearm vasculature was measured by plethysmography. The vasodilator response to acetylcholine was significantly blunted in hypercholesterolemic patients compared with normal controls (maximal flow 8.8 +/- 2 vs 12.7 +/- 3 ml/min/100 ml, respectively; p < 0.03); however, no difference was observed in the response to sodium nitroprusside (9.7 +/- 2 and 9.5 +/- 3 ml/min/100 ml). In normal controls, the infusion of superoxide dismutase did not significantly modify the response to acetylcholine (maximal flow 12.7 +/- 3 vs 12.1 +/- 3 ml/min/100 ml before and after superoxide dismutase, respectively). Similarly, in hypercholesterolemic patients, the infusion of superoxide dismutase did not alter the response to acetylcholine (maximal flow 8.8 +/- 2 and 8.9 +/- 2 ml/min/100 ml). A subset of 19 subjects (8 normal and 11 patients) received a 60-minute infusion of superoxide dismutase at 24,000 U/min without alteration in their response to acetylcholine.(ABSTRACT TRUNCATED AT 250 WORDS)
This study showed that endothelial dysfunction is present in men 3 to 6 months after myocardial infarction, but was unable to show any improvement in endothelial function after 3 months of therapy with vitamin E 800 IU/day. Further studies are necessary to determine whether higher doses or a longer course of vitamin E, or whether other antioxidant agents with or without lipid-modifying activity, would improve endothelial function.
BACKGROUND: Coronary endothelium plays a key role in the regulation of coronary tone, platelet adhesion, and aggregation, which are important factors in triggering acute cardiovascular events. However, its role in modulating the effects of circadian variations on coronary tone is not known. METHODS AND RESULTS: Responses of 72 nonstenotic coronary segments to acetylcholine and nitroglycerin were measured in 12 patients with chronic stable angina at 6 AM and 1 PM. After baseline angiography, three infusions of acetylcholine (10(-6), 10(-5), and 10(-4) mol/L) were administered selectively into the left coronary artery, followed by nitroglycerin. Diameters (in millimeters) of proximal, middle, and distal segments were measured by quantitative techniques. Forty-seven segments showed a constrictor response to acetylcholine (group 1, dysfunctional endothelium), and 25 other segments showed a dilator response (group 2, normally functioning endothelium). In group 1, the constrictor response to acetylcholine was significantly greater in the morning than in the afternoon (23 +/- 3% and 10 +/- 1%, mean +/- SEM, respectively; P < .001), and the dilator response to nitroglycerin was also significantly greater in the morning than in the afternoon (19 +/- 2% and 11 +/- 2%; P < .01). In group 2, the dilator response to acetylcholine did not differ significantly between the morning and afternoon (22 +/- 3% and 17 +/- 2%, respectively; P = NS), and the dilator response to nitroglycerin was also similar at both times of the day (30 +/- 3% and 28 +/- 4%, respectively; P = NS). CONCLUSIONS: Coronary segments with dysfunctional endothelium exhibit an early morning exaggeration in vasomotor activity, whereas segments with normally functioning endothelium do not show circadian variations. This suggests a potential protective role for the endothelium in modulating variations in coronary tone that may contribute to increased incidence of cardiovascular events in the early morning hours.