Long-term dietary nitrite and nitrate deficiency causes the metabolic syndrome, endothelial dysfunction and cardiovascular death in mice.

AIMS/HYPOTHESIS: Nitric oxide (NO) is synthesised not only from L-arginine by NO synthases (NOSs), but also from its inert metabolites, nitrite and nitrate. Green leafy vegetables are abundant in nitrate, but whether or not a deficiency in dietary nitrite/nitrate spontaneously causes disease remains to be clarified. In this study, we tested our hypothesis that long-term dietary nitrite/nitrate deficiency would induce the metabolic syndrome in mice. METHODS: To this end, we prepared a low-nitrite/nitrate diet (LND) consisting of an amino acid-based low-nitrite/nitrate chow, in which the contents of L-arginine, fat, carbohydrates, protein and energy were identical with a regular chow, and potable ultrapure water. Nitrite and nitrate were undetectable in both the chow and the water. RESULTS: Three months of the LND did not affect food or water intake in wild-type C57BL/6J mice compared with a regular diet (RD). However, in comparison with the RD, 3 months of the LND significantly elicited visceral adiposity, dyslipidaemia and glucose intolerance. Eighteen months of the LND significantly provoked increased body weight, hypertension, insulin resistance and impaired endothelium-dependent relaxations to acetylcholine, while 22 months of the LND significantly led to death mainly due to cardiovascular disease, including acute myocardial infarction. These abnormalities were reversed by simultaneous treatment with sodium nitrate, and were significantly associated with endothelial NOS downregulation, adiponectin insufficiency and dysbiosis of the gut microbiota. CONCLUSIONS/INTERPRETATION: These results provide the first evidence that long-term dietary nitrite/nitrate deficiency gives rise to the metabolic syndrome, endothelial dysfunction and cardiovascular death in mice, indicating a novel pathogenetic role of the exogenous NO production system in the metabolic syndrome and its vascular complications.

A case of coronary subclavian vertebral steal syndrome successfully treated with stenting to the stenosis of left subclavian artery.

Coronary subclavian vertebral steal syndrome (CSVSS) is a rare but important complication of coronary artery bypass graft surgery (CABG) when an internal mammary artery (IMA) is used. This syndrome is defined as a retrograde flow from coronary artery via the IMA and the vertebral artery to the subclavian artery due to a proximal subclavian artery stenosis. We describe a case of a 64-year-old female who underwent CABG, complaining of dyspnea and chest pain by exercise of left arm, and dizziness when she turned her face to the left. Her blood pressure was 113/69 mmHg in the left arm and 137/84 mmHg in the right arm. Coronary angiography revealed retrograde flow from the left anterior descending (LAD) artery to the left IMA. Aortography showed that the ostium of the left subclavian artery had a severe stenosis and that the left vertebral artery was visualized retrogradely. Thereby, the diagnosis of CSVSS was made. The stenosis of the left subclavian artery was successfully treated with a percutaneous transluminal angioplasty and stent implantation, resulting in the restoration of antegrade flow from the left IMA to the LAD artery and from the left subclavian artery to the left vertebral artery. She was discharged with no chest pain and dizziness. .

A case of Kounis syndrome associated with transcatheter arterial chemoembolization for hepatocellular carcinoma.

Kounis syndrome, which is known as allergic angina and allergic myocardial infarction today, was described as the coexistence of acute coronary syndrome with allergic reactions in 1991 by Kounis and Zavras. We report a case of a 79-year-old man with hypertension, hepatocellular carcinoma (HCC), and no allergic history. He had received transcatheter arterial chemoembolization (TACE) for treatment of HCC five times without allergic reactions. At the sixth time of TACE, he presented an anaphylactic reaction such as systemic erythema and severe arterial hypotension. Simultaneously, he complained of anterior chest pain and electrocardiogram showed significant ST segment elevation in inferior leads, indicating inferior myocardial infarction. Emergency coronary angiography, however, did not demonstrate any organic stenoses or occluded lesions of the coronary arteries. We made the diagnosis of Kounis syndrome associated with TACE. Although Kounis syndrome is a rare condition, physicians should be aware of possible co-occurrence of anaphylactic reactions and acute coronary syndrome. .

Chronic Helicobacter pylori infection is associated with peripheral arterial disease.

It is reported that Helicobacter pylori infection is associated with coronary atherosclerosis both epidemiologically and pathogenetically, but no conclusions have yet been reached. Therefore, we investigated the relationship between H. pylori infection and peripheral arterial disease (PAD). Sixty-nine patients with PAD attending Harasanshin General Hospital (Fukuoka, Japan) were compared with 143 controls (age-matched asymptomatic outpatients with hyperlipidemia). H. pylori infection was diagnosed by the detection of IgG antibodies, the (13)C-urea breath test, and histological examination. Multiple logistic regression analysis was used to assess the data. The 69 PAD patients and 143 controls were aged from 50 to 92 years. According to the Fontaine classification, 43/69 PAD patients (62.3%) were grade I, 25 (36.2%) were grade II, and 1 (0.14%) was grade III. The prevalence of H. pylori infection was higher in the PAD patients than in the controls (79.7% versus 44.8%; P < 0.01). Stepwise logistic regression analysis revealed that H. pylori infection and hypertension had a significant influence on the occurrence of PAD. Our results suggest that chronic H. pylori infection may be one of the risk factors for PAD.

Association between chronic Helicobacter pylori infection and acute ischemic stroke: Fukuoka Harasanshin Atherosclerosis Trial (FHAT).

Helicobacter pylori (H. pylori) have been associated both epidemiologically and pathogenetically with coronary atherosclerosis, but data on the relationship between chronic H. pylori infection and stroke are lacking. Therefore, we investigated the relationship between H. pylori infection and acute ischemic stroke in 62 patients with their first stroke and 143 controls. The stroke patients were all admitted to Harasanshin General Hospital (Fukuoka, Japan) and the controls were asymptomatic age-matched outpatients with hyperlipidemia who did not have cardiac disease or infections. All patients underwent cranial CT scanning and/or brain magnetic resonance imaging, duplex ultrasonography of the extracranial carotid arteries, and transthoracic echocardiography. H. pylori infection was diagnosed by detection of anti-H. pylori IgG antibodies, the 13C-urea breath test, and histology. Conditional logistic regression analysis was performed to analyze the data. The 62 stroke patients and 143 controls were aged from 41 to 92 years. Chronic H. pylori infection was associated with a higher risk of stroke due to small artery occlusion (odds ratio: 9.68; 95% CI: 3.56-33.08, P <0.001) and a lower risk of cardioembolic stroke (odds ratio: 0.27; 95% CI: 0.03-1.53). Chronic H. pylori infection still showed an overall association with ischemic stroke (odds ratio for all subtypes combined: 2.57; 95% CI: 1.09-6.08) after adjusting for major cardiovascular risk factors. These results suggest that chronic H. pylori infection may be a triggering factor that increases the risk of acute ischemic stroke.