Enhanced insulin response relates to acetylcholine-induced vasoconstriction in vasospastic angina

Shimabukuro, Michio; Shinzato, Takashi; Higa, Satoshi; Chibana, Takao; Yoshida, Hisashi; Nagamine, Fumio; Murakami, Keiji; Takasu, Nobuyuki

doi:10.1016/0735-1097(94)00381-y

Cited by 42 publications

(25 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We have confirmed the close relationship between insulin resistance and atherothrombotic cerebral infarction with angiographically proven carotid artery stenosis (15). Recent clinical evidence has shown a possible link between diminished coronary vasodilator response to acetylcholine and hyperinsulinemia in patients with vasospastic angina (4,5). On the other hand, the response of coronary blood flow to N G -monomethyl-L-arginine (L-NMMA), a competitive inhibitor of NOS, were reduced in patients with vasospastic angina and antioxidant treatment restored endothelial function in these patients (1,2).…”

Section: Insulin Resistance and Cardiovascular Diseasessupporting

confidence: 60%

“…In fact, insulin resistance states are commonly coexistent with defective insulin-mediated and endothelium-dependent vasodilatation (1 -3). Endothelial damage is of considerable clinical importance because the endothelium is considered to play a central role in the pathogenesis of atherosclerosis, and endothelial dysfunction has been implicated preceding to and likely contributing to the development of cardiovascular disease in these states (4,5). On the other hand, resistance to insulin action on augment blood flow responses was also demonstrated in the insulin-resistant state.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Stress and Vascular Responses: Oxidative Stress and Endothelial Dysfunction in the Insulin-Resistant State

et al. 2003

View full text Add to dashboard Cite

Abstract. Although insulin-resistant states have been associated with endothelial dysfunction due to increased vascular oxidative stress, the underlying mechanisms are pooly understood. Recent experimental evidence suggests that tetrahydrobiopterin (BH 4 ), the natural and essential cofactor of NO synthases (NOS), plays a crucial role not only in increasing the rate of NO generation by NOS but also in controlling the formation of superoxide anion (O 2 -) in endothelial cells. Because insulin resistance has been suggested to be a significant contributing factor in the development of abnormal pteridine metabolism and endothelial dysfunction, we investivated pteridine content and NO/ O 2 -production with the use of isolated thoracic aortas obtained from fructose-induced insulin-resistant rats. Under insulin-resistant conditions where BH 4 levels are suboptimal, the production of O 2 -by NOS leads to endothelial dysfunction. Furthermore, oral supplementation of BH 4 restores endothelial function and relieved oxidative tissue damage, at least in part, through activation of endothelial NOS (eNOS) in the aorta of insulin-resistant rats. These results indicate that insulin resistance may be a pathogenic factor for endothelial dysfunction through impaired eNOS activity and increased oxidative breakdown of NO due to enhanced formation of O 2 -, which are caused by relative deficiency of BH 4 in vascular endothelial cells.

show abstract

Section: Insulin Resistance and Cardiovascular Diseasessupporting

confidence: 60%

Section: Introductionmentioning

confidence: 99%

Stress and Vascular Responses: Oxidative Stress and Endothelial Dysfunction in the Insulin-Resistant State

et al. 2003

View full text Add to dashboard Cite

show abstract

“…It has recently been proposed that insulin resistance or hyperinsulinaemia may induce coronary hypervasoconstriction and microvascular dysfunction. 39,40 It has also been suggested that endothelial cell function may be impaired in non-stenotic systemic arteries in patients with FH. 41 It has also been shown that hypercholesterolaemia is associated with abnormal endothelium-dependent vasomotion in both the epicardial and resistance coronary arteries.…”

Section: Discussionmentioning

confidence: 99%

Importance of intra-abdominal visceral fat accumulation to coronary atherosclerosis in heterozygous familial hypercholesterolaemia

et al. 1997

View full text Add to dashboard Cite

OBJECTIVES: Hyper-low-density lipoprotein (LDL)-cholesterolaemia is a potent risk factor for coronary atherosclerosis. We have recently demonstrated that a cluster of risk factors including insulin resistance, glucose intolerance, hypertriglyceridaemia, and hypertension based on intra-abdominal visceral fat accumulation are closely related to coronary artery disease. In the current study, we evaluated the relationship between visceral fat accumulation and the severity and distribution of coronary atherosclerosis in familial hypercholesterolaemia (FH). DESIGN: The effect of visceral fat accumulation on coronary lesions and risk factors in patients with FH was investigated. SUBJECTS: Thirty-one male patients with heterozygous FH who underwent coronary angiography. MEASUREMENTS: Abdominal fat distribution was estimated by a cross-sectional computed tomographic scan at the umbilical level. Plasma lipid, glucose and insulin concentrations and blood pressure were measured. A 75 g oral glucose tolerance test was also performed. RESULTS: The patients were divided into two groups according to the degree of visceral fat accumulation. Fifteen patients had high visceral fat accumulation (High VF group) and 16 patients had normal visceral fat accumulation (Normal VF group). Body mass index (BMI) and subcutaneous fat area were signi®cantly higher in the high VF group. Baseline serum triglyceride was signi®cantly higher and baseline low-density lipoprotein (LDL)-cholesterol and reduction of LDL-cholesterol during treatment were signi®cantly lower in High VF group. Fasting plasma glucose and insulin concentrations, and systolic and diastolic pressures were signi®cantly higher in the High VF group. Signi®cant correlations were found between visceral fat area and the sum of the glucose and insulin concentration during an oral glucose tolerance test. Visceral fat area was signi®cantly correlated with the severity of coronary stenosis index. Distal coronary lesions were signi®cantly more frequent in the High VF group. moreover, the correlation between the visceral fat area and coronary stenosis index was found to be independent of age, BMI, and subcutaneous fat area by multiple regression analysis. CONCLUSIONS: Visceral fat accumulation is a potent cardiovascular risk factor in heterozygous FH.

show abstract

“…These results suggest that the endothelial cells that line the epicardial artery of individuals with IR are functionally abnormal, which is in accordance with previous findings that enhanced insulin response is related to Ach-induced vasoconstriction in patients with vasospastic angina. 11,12 To estimate the function of the endothelial cells that line the coronary artery, we measured the APV through the coronary artery after administration of Ach, and found it was less in the IR patients than in the NIR patients. When a higher concentration of Ach was administered, the APV in the IR group was reduced further.…”

Section: Discussionmentioning

confidence: 99%

Effect of Insulin Resistance on the Endothelial Vasomotor Function of the Coronary Artery of Nondiabetic Patients

et al. 1999

View full text Add to dashboard Cite

nsulin resistance is a state in which cells and organs have decreased sensitivity to insulin and individuals with insulin resistance have reduced glucose uptake. 'Syndrome X', proposed by Reaven in 1988, 1 is characterized by insulin resistance, abnormal glucose tolerance, hyperinsulinemia, increased VLDL-triglyceride, decreased HDL-cholesterol, and hypertension. He reported that patients with this syndrome have a high risk for ischemic heart disease. Kaplan added the concept of obesity to Syndrome X. 2 The 'deadly quartet' is characterized by upper-body obesity, glucose intolerance, hypertriglycemia, and hypertension. Thus, insulin resistance is associated not only with metabolic diseases, but also with arteriosclerotic diseases such as ischemic heart disease. We studied the relationship between insulin resistance and the endothelial vasomotor function of the coronary artery of nondiabetic patients, and discuss the significance of insulin resistance in coronary artery disease (CAD). Methods Study SubjectsTwenty-five subjects with chest symptoms and a positive exercise tolerance test, who did not have diabetes mellitus by the hemoglobin A1C test and the fasting value of blood glucose (FBS), were included in this study. None Japanese Circulation Journal Vol.63, August 1999 of the subjects had significant stenosis of the right coronary artery (RCA); the stenosis in each case was less than 25% by American Heart Association (AHA) classification. Written informed consent was obtained from all 25 patients and their family members after explaining the protocol of the present study. The patients ranged in age between 39 and 68 years (mean ± SD: 57.2±9.1), and included 15 females and 10 males. Coronary Flow VelocityAbsence of significant stenosis of the RCA was confirmed by the Judkins technique. A 0.018F flow wire (Cardiometrics, Mountain View, CA, USA) was inserted into the RCA to measure the coronary flow velocity, which was measured after it became steady. Following initial measurement of the baseline velocity, physiological saline was injected into the RCA at an infusion rate of 1 ml/min through a 5F Judkins catheter for 2 min. The following drugs were then each injected at least 5 min after administration of the previous drug and after the initial flow velocity was restored. First, acetylcholine (Ach; Daiichi Seiyaku, Tokyo, Japan) at a concentration of 2 g ml -1 min -1 was injected for 2 min. The average peak flow velocity (APV) and coronary angiogram were recorded. When the flow velocity returned to its initial level, 20 g ml -1 min -1 of Ach was injected for 2 min after which the APV and coronary angiogram were recorded. Next, 10 mg of papaverine hydrochloride (PAP; Nihon Seiyaku, Tokyo, Japan) was injected over 5 s, soon after which the APV and coronary angiogram were recorded. Finally, a bolus dose (2 mg) of isosorbide dinitrate (ISDN; Eisai, Tokyo, Japan) was injected, and again the APV and coronary angiogram were recorded. The coronary artery flow velocity, blood pressure, heart rate, and 12-lead electroc...

show abstract

Enhanced insulin response relates to acetylcholine-induced vasoconstriction in vasospastic angina

Abstract: Results show that acetylcholine-induced coronary vasoconstriction in subjects with vasospastic angina correlates with hyperinsulinemia and enhanced insulin response, suggesting insulin resistance syndrome as a feature of vasospastic angina.

Cited by 42 publications

References 36 publications

Stress and Vascular Responses: Oxidative Stress and Endothelial Dysfunction in the Insulin-Resistant State

Stress and Vascular Responses: Oxidative Stress and Endothelial Dysfunction in the Insulin-Resistant State

Importance of intra-abdominal visceral fat accumulation to coronary atherosclerosis in heterozygous familial hypercholesterolaemia

Effect of Insulin Resistance on the Endothelial Vasomotor Function of the Coronary Artery of Nondiabetic Patients

Contact Info

Product

Resources

About