Effects of carvedilol on vascular reactivity in human left internal mammary artery.

OBJECTIVE: Surgical treatment choice for coronary artery disease is coronary artery bypass grafting (CABG) surgery. Left internal mammary artery (LIMA) is frequently used as an arterial graft in CABG operations. Perioperative spasm of LIMA can result in increased morbidity and mortality. Pharmacological interventions are routinely used for prevention and treatment of LIMA spasm. In this study, we aimed to investigate the effects of carvedilol, an alpha- and beta-adrenergic receptor blocker, on responses to endogenous vasoconstrictors which play a role in graft spasm and the possible interaction between carvedilol and diltiazem/papaverine which are vasodilators commonly used in CABG surgery. PATIENTS AND METHODS: Isolated LIMA rings collected from patients undergoing CABG operation were suspended in an organ bath. Concentration-dependent responses to norepinephrine (NE), serotonin (5-HT) and diltiazem were examined before and after carvedilol incubation (10-6 M, 1 hour). Maximum relaxation response to papaverine (10-4 M) was compared in LIMA rings incubated with 0.05% dimethyl sulfoxide (DMSO, placebo) or carvedilol (10-6 M). RESULTS: Carvedilol did not affect the maximal contractile response to NE; however, it significantly reduced the sensitivity of LIMA to NE. Carvedilol increased contractile response and sensitivity to 5-HT. Promisingly, carvedilol increased the vasodilatory effects of diltiazem and papaverine. CONCLUSIONS: Our study suggests that carvedilol may be administered perioperatively in combination with diltiazem or papaverine to prevent or resolve LIMA graft spasm.

Ergothioneine produces relaxation in isolated rat aorta by inactivating superoxide anion.

OBJECTIVE: Ergothioneine (EGT) is a ubiquitous, sulphur-containing derivative of amino acid histidine, acquired by higher order plants and animals solely through dietary means. The antioxidant and cytoprotective effects of ergothioneine have been demonstrated by in vitro studies, but its physiological role remains unclear. This study aims to investigate the effects of ergothioneine (EGT) on basal and acetylcholine-stimulated activity of nitric oxide. MATERIALS AND METHODS: Effects of EGT on basal and acetylcholine (ACh)-stimulated activity of nitric oxide (NO) were tested in isolated rings of rat thoracic aorta. In parallel experiments, relaxant responses to ACh were evaluated following incubation with Cu/Zn superoxide dismutase inhibitor diethyldithiocarbamate (DETCA) and superoxide anion generating system hypoxanthine/xanthine oxidase (HX/XO). Generation of reactive oxygen species (ROS) in aortic rings was measured by means of lucigenin- and luminol-enhanced chemiluminescence, in the presence and in the absence of EGT. RESULTS: EGT (1-200 µM) produced a concentration-dependent relaxation in endothelium-intact aortic rings which was abolished by endothelial denudation or NO synthase inhibition. Impaired response to ACh in DETCA and HX/XO treated rings was recovered by EGT treatment. This recovery by EGT was characterized by a significant decrease in the production of superoxide anion. CONCLUSIONS: Ergothioneine, at levels normally present in blood, may protect NO from destruction by superoxide anion and play a physiologically important role in preserving NO-dependent endothelial function.