Nitric oxide production by coronary conductance and resistance vessels in hypercholesterolemia patients

Shiode, Nobuo; Nakayama, Kensyo; Morishima, Nobuyuki; Yamagata, Togo; Matsuura, Hideo; Kajiyama, Goro

doi:10.1016/s0002-8703(96)90076-9

Cited by 29 publications

(9 citation statements)

References 28 publications

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“…54,55 Therefore, ⑀2 might cause endothelial dysfunction resulting in the production of free radical superoxide anions, thus causing the deactivation of nitric oxide. 56,57 Endothelial dysfunction in thrombotic vessels might hypothetically enhance or facilitate dislodgment of thrombi/emboli, thus causing embolic stroke.…”

Section: Discussionmentioning

confidence: 99%

Age-Dependent Association of Apolipoprotein E Genotypes With Stroke Subtypes in a Japanese Rural Population

Kokubo

Chowdhury

Date

et al. 2000

Stroke

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Background and Purpose-The association between apolipoprotein E (apoE) polymorphisms and stroke has been controversial. These controversies may be due to inaccurate classification of stroke and differences in age ranges. We investigated the association between apoE genotypes and stroke subtypes (confirmed by CT or MRI findings) by case-control study in a Japanese rural population. Methods-First-ever-stroke patients (nϭ322; cerebral infarction, nϭ201, intracerebral hemorrhage, nϭ84, and subarachnoid hemorrhage, nϭ37) aged 40 to 89 years were recruited from Hokuetsu Hospital, Japan. Healthy controls (nϭ1126) were selected from the general population in the same area. ApoE genotypes were determined by restriction fragment-length polymorphism analysis. Results-Compared with apoE ⑀3/⑀3 subjects, ⑀2 carriers had a 2-fold risk of cerebral infarction (OR 1.9, 95% CI 1.1 to 3.2). Among cerebral infarction patients, ⑀2 carriers had increased risks of cortical infarction (OR 2.4, 95% CI 1.3 to 4.6) (an anatomic subtype) and atherothrombosis (OR 3.9, 95% CI 1.7 to 9.0) and cardioembolism (OR 4.9, 95% CI 1.6 to 14.4) but not lacunar infarction (clinical subtypes). ApoE ⑀4 carriers had a 2.5-fold risk of subarachnoid hemorrhage (OR 2.5, 95% CI 1.1 to 5.4). ApoE ⑀2/⑀2 subjects had an increased risk of intracerebral hemorrhage (OR 4.4, 95% CI 1.0 to 19.7). ApoE ⑀3/⑀4 subjects showed Ϸ2-fold increased risk of atherothrombosis (OR 2.1, 95% CI 1.0 to 4.1) and intracerebral hemorrhage (OR 1.8, 95% CI 1.0 to 3.3). The association between ⑀2 and stroke was accentuated in subjects aged 70 years or older but not in those aged 40 to 69 years. Conclusions-Our study suggests that apoE ⑀2 is a risk factor for atherothrombosis, cardioembolism, and intracerebral hemorrhage, whereas ⑀4 is a risk factor for atherothrombosis, intracerebral hemorrhage, and subarachnoid hemorrhage. The occurrence of stroke may be affected by interaction between age and apoE gene polymorphisms. (Stroke.

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Section: Discussionmentioning

confidence: 99%

Age-Dependent Association of Apolipoprotein E Genotypes With Stroke Subtypes in a Japanese Rural Population

Kokubo

Chowdhury

Date

et al. 2000

Stroke

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“…This difference between effects of risk factors on basal and stimulated nitric oxide has also been observed for other risk factors, such as hypercholesterolemia and hyperhomocysteinemia. 16,17 It is also possible that L-NMMA may not be the best method to test for effects of xanthine oxidase inhibition. This is because nitric oxide synthase produces superoxide radicals, 18 which are decreased by allopurinol, and this could lead to feedback amplification of nitric oxide synthase.…”

Section: Discussionmentioning

confidence: 99%

Xanthine Oxidase Inhibition Reverses Endothelial Dysfunction in Heavy Smokers

et al. 2003

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Background-Cigarette smoking causes endothelial dysfunction, possibly through increased oxidant stress. The enzyme xanthine oxidase produces oxidative free radicals. We tested the hypothesis that xanthine oxidase contributes to endothelial dysfunction in cigarette smokers by administering the inhibitor allopurinol. Methods and Results-Fourteen cigarette smokers (31Ϯ4 pack years) and 14 age-and sex-matched healthy non-smoking control subjects participated in a single-blinded, randomized, 2-phase crossover study. All subjects had no other risk factors for atherosclerosis. Inhibition of xanthine oxidase was achieved by a single oral dose of 600 mg of allopurinol on the day of the study. Stimulated nitric oxide endothelial responses were assessed by forearm blood flow responses to intraarterial administration of acetylcholine and bradykinin 4 to 7 hours later; basal nitric oxide was assessed using the nitric oxide synthase inhibitor NG-monomethyl-L-arginine (L-NMMA); and nitroprusside was used to assess sensitivity to nitric oxide. Dilatation produced by acetylcholine was significantly less in smokers (254Ϯ57%) than healthy controls (390Ϯ55%) (Pϭ0.009). Allopurinol reversed endothelial dysfunction in smokers (acetylcholine, 463Ϯ78%, Pϭ0.001) without affecting responses in non-smokers (401Ϯ80%). Bradykinin responses were also impaired in smokers (Pϭ0.003), and improved with allopurinol, though not significantly (Pϭ0.06). Responses to nitroprusside and L-NMMA were not significantly different between smokers and controls and were not altered by allopurinol. Conclusions-Smoking-induced endothelial dysfunction of resistance vessels is rapidly reversed with oral allopurinol.These data suggest that xanthine oxidase contributes importantly to endothelial dysfunction caused by cigarette smoking.

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“…26,27 Although attenuation of the vasoconstrictor response to ACh might not be equal to the improvement in endothelial function, studies of human coronary endothelial function have largely relied on stimulating NO bioavailability with ACh. 10,[28][29][30] Therefore, we estimated the BH4-induced improvement in coronary endothelial function by measuring the change in coronary diameter in response to ACh.…”

Section: Study Limitationsmentioning

confidence: 99%

Tetrahydrobiopterin Improves Coronary Endothelial Function, But Does Not Prevent Coronary Spasm in Patients With Vasospastic Angina

Fukuda

Teragawa

Matsuda

et al. 2002

Circ J

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oronary spasm is believed to play an important role in the pathogenesis of vasospastic angina (VA) and can cause acute myocardial infarction or ischemic sudden death. 1 However, the precise pathophysiology of coronary spasm has yet to be elucidated, although coronary endothelial dysfunction is thought to be one of the mechanisms. 2,3 Tetrahydrobiopterin (BH4) is an essential cofactor for nitric oxide (NO) synthase in both endothelial and vascular smooth muscle cells [4][5][6] and also serves as a scavenger of oxygen-derived free radicals, thereby decreasing NO breakdown. 7 Therefore, BH4 is considered essential for the regulation of NO bioavailability in endothelial cells and for the maintenance of cardiovascular homeostasis. In support of this concept, recent studies have shown that supplementation of BH4 improves impaired endothelial function in humans with various pathologic states, including hypercholesterolemia, smoking and coronary artery disease. [8][9][10][11] Because coronary endothelial dysfunction is commonly observed in patients with VA, 3,12,13 the depletion of BH4 and resultant reduction in NO bioavailability in the coronary circulation may be involved in the pathogenesis of coronary spasm. However, the effects of BH4 supplementation on coronary spasm have not been evaluated and so we investigated the effects of BH4 on the coronary vasoconstrictor response to acetylcholine (ACh) in patients with VA using quantitative coronary angiography. Methods Study PopulationWe enrolled 28 Japanese patients with VA (21 men, 7 women; mean age, 55 years; range, 38-70) who fulfilled the following inclusion criteria: (1) spontaneous chest pain associated with ST-segment elevation or depression at rest on 12-lead ECG or ambulatory ECG; (2) coronary spasm (≥50% reduction in arterial diameter during coronary angiography) in the left coronary artery associated with ST-segment changes and/or typical chest pain after intracoronary injection of ACh (Daiichi Pharmaceutical Co, Tokyo, Japan); and (3) no angiographic organic stenosis in the coronary arteries. Patients with severe left ventricular dysfunction and those with valvular heart disease were excluded. Written consent was obtained from each patient, and the protocol was approved by the Hiroshima University School of Medicine Ethics Committee. Study DesignThe study design has been described previously in detail. 14,15 Briefly, anti-anginal therapy was withheld for at least 48 h before cardiac catheterization, except for unrestricted use of sublingual nitroglycerin (NTG). Diagnostic right and left heart catheterization and coronary angiography were performed using the standard percutaneous femoral approach. A 6Fr guide catheter was introduced into the left main coronary artery, and a 5Fr temporary pacing electrode catheter (Bard, Tewksbury, MA, USA) was placed in the right ventricular apex via the right jugular vein and connected to a temporary pacemaker set at a rate of 50 beats/min. Study ProtocolAfter baseline conditions were established, incremental

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Nitric oxide production by coronary conductance and resistance vessels in hypercholesterolemia patients

Cited by 29 publications

References 28 publications

Age-Dependent Association of Apolipoprotein E Genotypes With Stroke Subtypes in a Japanese Rural Population

Age-Dependent Association of Apolipoprotein E Genotypes With Stroke Subtypes in a Japanese Rural Population

Xanthine Oxidase Inhibition Reverses Endothelial Dysfunction in Heavy Smokers

Tetrahydrobiopterin Improves Coronary Endothelial Function, But Does Not Prevent Coronary Spasm in Patients With Vasospastic Angina

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