Vasomotor Responses Of Coronary Arteries Research Articles

Association of Ornithine Transcarbamylase Gene Polymorphisms With Hypertension and Coronary Artery Vasomotion

Previous studies have suggested that the activity of enzymes involved in the urea cycle may modulate nitric oxide (NO) production, arterial vasomotion, and hypertension. Our aim was to determine whether hypertension and coronary vasomotion could be associated with polymorphisms within the ornithine transcarbamylase (OTC) gene, located on chromosome X and coding for a key-enzyme of the urea cycle. Among 11 OTC polymorphisms that were originally selected from databases, the tag single-nucleotide polymorphism (SNP) rs5963409 and the independent SNP rs1800321 were tested for association with hypertension in two independent population samples recruited in Northern (Multinational MONItoring of trends and determinants in CArdiovascular disease (MONICA) study, n = 1,138) and Western (Etude du Vieillissement Artériel (EVA) study, n = 1,166) France. The vasomotor response of coronary arteries to methylergonovine maleate and isosorbide dinitrate was also evaluated in an independent sample (the vasomotion study, n = 121). In males, the frequency of the rs5963409 minor allele was consistently higher in hypertensive (HT) than in normotensive subjects in the MONICA and EVA studies. In the combined sample, the rs5963409 minor allele was associated with an increased risk of hypertension (odds ratio (OR) (95% confidence interval (CI)) = 1.45 (1.10-1.90); P = 0.008). This association was independent of classical confounding factors. Consistently, rs5963409 minor allele was associated with a greater susceptibility to vasoconstriction in response to methylergonovine maleate (P = 0.0072). In contrast, no significant association between rs5963409 and hypertension could be detected in females. Our results suggest that the OTC rs5963409 polymorphism may be associated with hypertension and coronary vasomotion in males.

Clinical Benefits of a Metabolic Approach in the Cardiac Rehabilitation of Patients with Coronary Artery Disease

Patients referred for cardiac rehabilitation may benefit from combining trimetazidine with exercise training because both treatments produce synergic benefits on the cardiovascular system. There is evidence that trimetazidine improves left ventricular (LV) function in patients with ischemic and diabetic cardiomyopathy by shifting the cellular energy substrate reference from fatty acids to glucose oxidation, and that this effect is associated with a better outcome. Recently, results have demonstrated that trimetazidine improves radial artery endothelium-dependent relaxation related to its antioxidant properties. Similarly, exercise training has been demonstrated to improve diastolic filling and systolic function in patients with ischemic cardiomyopathy, in relation to enhanced perfusion and contractility of dysfunctional myocardium. Patients with viable myocardium, in theory, should have the greatest benefits because trimetazidine improves contractility of dysfunctional hibernating/stunned myocardium, whereas exercise has documented efficacy in improving endothelial vasomotor response of coronary arteries, stimulating coronary collateral circulation and small vessel growth, improving LV function, and increasing functional capacity. At present, there are no published reports about the efficacy of the combination of trimetazidine with exercise training. In this article, we discuss the rationale for using trimetazidine in cardiac rehabilitation, the identification of patients referred for cardiac rehabilitation who might benefit the most from the addition of trimetazidine to standard therapy, and the documented benefits.

P3327 Relationship between cholesterol level, smoking status and vasomotor responses of coronary arteries to L-arginine

P3327 Relationship between cholesterol level, smoking status and vasomotor responses of coronary arteries to L-arginine

Comparison of the effects of exercise and cold pressor test on the vasomotor response of normal and atherosclerotic coronary arteries and their relation to the flow-mediated mechanism

This study was designed to assess the vasomotor response of coronary arteries to exercise and the cold pressor test, and its relationships with the endotheliumediated dependent mechanism. Twenty-two patients were entered in the study. Group 1 was composed of 12 patients with a total cholesterol level < 200 mg/dl associated with angiographically smooth, normal coronary arteries. Group 2 consisted of 10 patients with both a cholesterol level >240 mg/dl and angiographic luminal irregularities of the left anterior descending coronary artery. Coronary blood flow was assessed by a 0.018-inch tip guidewire during Doppler ultrasonography, and analysis of the coronary arterial dimension of the midportion of the left anterior descending coronary artery was performed by quantitative coronary angiography. Catecholamine concentrations were assessed at the different stages of the protocol. The ratepressure product increased during both the cold pressor test and exercise (p < 0.001). Coronary blood flow velocity increased during the cold pressor and exercise tests by 24.5 ± 10% and 72 ± 42%, respectively (p < 0.001), and by 127 ± 62% (p < 0.0001) after administration of papaverine. In group 1, the cold pressor test had a more pronounced vasodilating effect on epicardial coronary arteries (+11.2 ± 16%) compared with group 2 (−2 ± 9%, p < 0.05). Similarly, exercise had a vasodilating action in group 1 (11.3 ± 15%) compared with group 2 (−1.9 ± 8%, p < 0.05). Both responses were highly correlated (r = 0.92, p < 0.001). Papaverine administration had a vasodilating action in patients from group 1 (11.6 ± 16%) compared with group 2 (−1.2 ± 8%, p < 0.05). Both the vasomotor responses to the cold pressor test and exercise were correlated to the response to papaverine administration, r = 0.90 and r = 0.92, respectively (all p < 0.001). Noradrenaline concentrations increased both during the cold pressor test and exercise (p < 0.05), but not after papaverine administration. These results show that the endothelium modulates the response of epicardial coronary arteries to sympathetic stimulation, mainly by a flowmediated mechanism.

Changing vasomotor responses of coronary arteries to nifedipine

Coronary vasomotion is influenced by a variety of factors, including atherosclerosis and diurnal variations in α-adrenergic tone. The effect of such factors on the coronary response to vasodilator drugs is unknown. To determine whether there is a diurnal variation to the response of coronary arteries to nifedipine, and whether this response is altered by atherosclerosis, we studied 11 patients with smooth coronary arteries, six in the morning and five in the afternoon, and 12 patients with irregular coronary arteries,, six in the morning and six in the afternoon. Changes in coronary blood flow and the vasomotor response of an epicardial coronary artery were measured before and after a 2 mg intracoronary infusion of nifedipine. There were no appreciable differences in epicardial vessel dilator response or coronary blood flow in the morning and afternoon among patients with smooth coronary arteries. By contrast, patients with irregular coronary arteries, had a significantly diminished dilator response in the afternoon, without an appreciable change in coronary blood flow. We postulate that normal coronary arteries maintain basal tone throughout the day. By contrast, atherosclerotic coronary arteries cannot do the same, increasing tone in the morning in response to catecholamines. When catecholamine levels drop in the afternoon, basal tone decreases in atherosclerotic vessels, and the dilator response to nifedipine is blunted. This observation may have an important impact on the expected benefits and timing of vasodilator therapy in patients with coronary artery disease.

Preserved endothelium-dependent vasodilation at the vasospastic site in patients with variant angina.

Endothelial dysfunction has been implicated as a cause of coronary vasospasm in patients with variant angina. This study aimed to determine if endothelium-dependent vasodilation evoked with substance P (SP) was altered at the spastic site where vasospasm was induced by acetylcholine (ACH) in patients with variant angina. It has been shown that SP evokes endothelium-dependent vasodilation with no direct effect on vascular smooth muscle in excised human coronary arteries. SP and ACH were infused into the coronary arteries in nine patients with variant angina in whom coronary arteriograms showed normal or mild atherosclerotic lesions. The vasomotor responses of coronary arteries were assessed by quantitative arteriography. ACH at a high dose (100 micrograms/min) provoked coronary vasospasm associated with anginal attack in all patients. In contrast, SP at graded doses (13.5, 40, and 135 ng/min) caused the dose-dependent and comparable increases in the coronary diameter at the spastic and control sites. ACH at a low dose (10 micrograms/min) also caused comparable vasodilation at the spastic and control sites in patients with normal coronary arteries. Coronary vasodilating responses to SP were comparable in patients with variant angina and those with atypical chest pain. The results indicate that endothelium-dependent vasodilation evoked with SP and ACH at the low dose was present at the vasospastic site in patients with variant angina. These findings suggest that the ACH-induced coronary vasospasm in patients with variant angina results from hyperreactivity of vascular smooth muscle to ACH but not from endothelial dysfunction.

The Effect of Atherosclerosis on the Vasomotor Response of Coronary Arteries to Mental Stress

Mental stress can cause angina in patients with coronary artery disease, but its effects on coronary vasomotion and blood flow are poorly understood. Because atherosclerosis affects the reactivity of coronary arteries to various stimuli, such as exercise, we postulated that atherosclerosis might also influence the vasomotor response of coronary arteries to mental stress. We studied 26 patients who performed mental arithmetic under stressful conditions during cardiac catheterization. (An additional four patients who did not perform the mental arithmetic served as controls.) Coronary segments were classified on the basis of angiographic findings as smooth, irregular, or stenosed. In 15 of the patients without focal stenoses in the left anterior descending artery, acetylcholine (10(-8) to 10(-6) mol per liter) was infused into the artery to test endothelium-dependent vasodilation. Changes in coronary blood flow were measured with an intracoronary Doppler catheter in these 15 patients. The response of the coronary arteries to mental stress varied from 38 percent constriction to 29 percent dilation, whereas the change in coronary blood flow varied from a decrease of 48 percent to an increase of 42 percent. The direction and magnitude of the change in the coronary diameter were not predicted by the changes in the heart rate, blood pressure, or plasma norepinephrine level. Segments with stenoses (n = 7) were constricted by a mean (+/- SE) of 24 +/- 4 percent, and irregular segments (n = 20) by 9 +/- 3 percent, whereas smooth segments (n = 25) did not change significantly (dilation, 3 +/- 3 percent; P less than 0.0002). Coronary blood flow increased by 10 +/- 10 percent in smooth vessels, whereas the flow in irregular vessels decreased by 27 +/- 5 percent. The degree of constriction or dilation during mental stress correlated with the response to the infusions of acetylcholine (P less than 0.0003, r = 0.58). Atherosclerosis disturbs the normal vasomotor response (no change or dilation) of large coronary arteries to mental stress; in patients with atherosclerosis paradoxical constriction occurs during mental stress, particularly at points of stenosis. This vasomotor response correlates with the extent of atherosclerosis in the artery and with the endothelium-dependent response to an infusion of acetylcholine. These data suggest that in atherosclerosis unopposed constriction caused by a local failure of endothelium-dependent dilation causes the coronary arteries to respond abnormally to mental stress.