Kiyoshi Takada

Attenuation of acetylcholine-induced vasoconstriction by L-arginine is related to the progression of atherosclerosis

To determine if L-arginine, a precursor of the endothelium-derived relaxing factor, restores endothelium-dependent dilation in human coronary arteries, we studied 21 patients in whom the lumina of the coronary arteries were angiographically smooth or slightly irregular and in whom there was a constrictor response to acetylcholine (ACh) in the left anterior descending coronary artery or the circumflex coronary artery. We examined the response to intracoronary ACh before and after infusion of L-arginine by measuring coronary diameter with quantitative angiography. Intracoronary injection of ACh produced vasoconstriction in the majority of patients with coronary risk factors. The percentage diameter change in smooth segments in patients with entirely smooth coronary arteries (group 1, n = 44) from baseline was -20.7% +/- 17.4%. During systemic infusion of L-arginine, the constrictor response to ACh in these segments was significantly attenuated (-2.2% +/- 15.1% from baseline, p < 0.01, ACh alone vs ACh during L-arginine infusion). In smooth segments in patients with luminal irregularities in the other coronary arteries (group 2, n = 19), ACh produced a marked constriction (-32.5% +/- 22.5% from baseline, p < 0.05, group 1 vs group 2). Infusion of L-arginine also attenuated ACh-induced vasoconstriction in these segments (-9.7% +/- 14.1% from baseline, p < 0.01, ACh vs ACh during L-arginine infusion). In segments with irregular lumina (group 3, n = 26), ACh produced more prominent vasoconstriction. The percentage diameter change was -40.9% +/- 26.5% from baseline (p < 0.01 vs group 1).(ABSTRACT TRUNCATED AT 250 WORDS)

A patient with diabetes mellitus, cardiomyopathy, and a mitochondrial gene mutation: confirmation of a gene mutation in cardiac muscle

A 44-year-old woman with diabetes mellitus, cardiomyopathy, and a mitochondrial gene mutation, was reported. She was diagnosed as having diabetes at 33 years of age and was treated with insulin. However, she stopped treatment 6 months later and had no medical care until she developed diabetic ketoacidosis at 41 years of age. She had diabetic foot, diabetic retinopathy, and nephropathy with low insulin secretory capacity, leading to insulin treatment. A point mutation of the mitochondrial tRNA(Leu(UUR)) gene was identified in peripheral leukocytes at 43 years of age, and sensorineural hearing impairment was detected at the same time. Her mother also suffered from diabetes mellitus with deafness and her son, who was not diabetic at age 19, had the same mitochondrial DNA (mtDNA) mutation. At 44 years of age, she developed congestive heart failure due to cardiomyopathy, and the same mtDNA mutation was identified in the cardiac muscle. Thus, it is very likely that in this patient, diabetes and cardiomyopathy was caused by the same abnormality, the point mutation of mitochondrial tRNA(Leu(UUR)) gene.