Effects of long-term administration of methionine on vascular endothelium in rabbits.

BACKGROUND AND AIM: We studied the effects of long-term methionine administration on the vascular endothelium of Japanese white rabbits. METHODS AND RESULTS: Eleven rabbits were divided into a control group (n = 6) and a methionine-fed group (n = 5), and reared for 22 weeks. Blood samples were collected at baseline and after 22 weeks for the measurement of serum homocysteine and cysteine, serum lipids and serum superoxide dismutase activity. At the end of experiments, the animals were sacrificed, and the thoracic aorta was removed for the measurement of isometric tension and histopathological examination. The blood samples taken from the methionine group in the 22nd week showed slight but significant increases in serum homocysteine and cysteine levels (Hcy: 13.7 +/- 1.4 vs 21.0 +/- 4.9, p < 0.01; Cys: 241.6 +/- 37.8 vs 342.6 +/- 35.0, p < 0.01). In the isometric tension experiments, the methionine group had a significantly decreased (p < 0.01) vasodilatation reaction induced by acetylcholine, an endothelium-dependent vasodilator. The histopathological examination (immunostaining in response to eNOS and tissue factor) showed significant increases in endothelium expression in the methionine group before atherosclerotic changes appeared. CONCLUSIONS: The above results suggest that vascular endothelial dysfunction played an important role in the atherosclerosis occurring after excess methionine feeding.

[Prediction of effect of beta-blocker therapy in patients with dilated cardiomyopathy by using 123I-BMIPP, 123I-MIBG scintigraphy].

We investigated prediction of the efficacy of beta-blocker therapy in patients with dilated cardiomyopathy (DCM) by using myocardial scintigraphy with 123I-BMIPP (BMIPP) and 123I-MIBG (MIBG). Thirty-seven patients with DCM were examined by myocardial scintigraphy with BMIPP and MIBG before beta-blocker therapy. Patients were classified into two groups, based on whether they improved > 10% of the left ventricular ejection fraction (LVEF) (improved group, n = 21) or not (unimproved group, n = 16). The extent and severity score of BMIPP for the improved group was significantly lower (p < 0.001) than that for unimproved group. It has been suggested that BMIPP is useful in evaluating the prediction of efficacy of beta-blocker therapy in patients with DCM.

Protective roles of endogenous carbon monoxide in neointimal development elicited by arterial injury.

We reported that carbon monoxide (CO) generated through heme oxygenase (HO) inhibits mitogen-induced proliferation of vascular smooth muscle cells (VSMCs). We report that balloon injury induces HO-1, the stress-inducible isozyme of HO, in VSMCs and inhibits neointimal formation through the action of endogenous CO. Northern blot analysis and immunohistochemistry revealed that HO-1 is markedly induced in the media as early as 1 day after injury, whereas only a little expression was detected in the intact carotid artery. The neointimal proliferative changes were augmented or inhibited by the HO inhibitors or inducer, respectively, and effects of these interventions were not altered by suppression of endogenous nitric oxide (NO), if any. To elucidate the mechanisms by which HO controls the proliferative changes, effects of alterations in the HO reaction were examined by determining angiotensin II-elicited VSMC proliferation in vitro: the HO inducer attenuated and its inhibitor restored the proliferative response to angiotensin II (1 nM and 100 nM). Hemoglobin, a reagent trapping both NO and CO, but not met-hemoglobin, which can capture NO but not CO, augmented the proliferative response. These data suggest that endogenous CO serves as a protective factor that limits the excessive VSMC proliferation associated with vascular diseases.

Evaluation of the cardiac autonomic nervous system in spontaneously non-insulin-dependent diabetic rats by 123I-metaiodobenzylguanidine imaging.

OBJECTIVE: To evaluate the sensitivity of 123I-labeled metaiodobenzylguanidine (123I-MIBG) scintigraphy in detecting diabetic autonomic nervous system disorders. MATERIALS AND METHODS: Thirty-one-week-old male Otsuka Long-Evans Tokushima Fatty (OLETF) rats, an animal model of spontaneous non-insulin-dependent diabetes mellitus, were maintained for 8 weeks with or without 30% sucrose solution as a drinking water (n = 3 each). Long-Evans Tokushima Otsuka (LETO) rats (n = 3), served as controls. Plasma glucose and insulin levels were measured, and 123I-MIBG scintigraphy was performed with a gamma camera equipped with a pinhole collimator for animals. Plasma and cardiac tissue cathecolamine levels were also determined. RESULTS: Plasma glucose levels of OLETF rats with and without sucrose loading (554+/-106 and 141+/-1.5 mg/dl respectively) were significantly higher than those of LETO rats (116+/-3.7 mg/dl). Norepinephrine concentrations in heart and plasma tended to be lower in diabetic rats. The washout rate of 123I-MIBG in diabetic rats was significantly higher than the rate in control rats. Cardiac uptake of 123I-MIBG, calculated as % dose/g of tissue, was significantly lower in diabetic rats than in control rats. CONCLUSION: These results suggest that myocardial 123I-MIBG scintigraphy is suitable for assessing cardiac sympathetic activity noninvasively in diabetic states, even in the early stages.