Coronary Vasomotor Research Articles

Nitrate-induced coronary vasodilation by stress-magnetic resonance imaging: a novel noninvasive test of coronary vasomotion.

To evaluate the feasibility of assessing coronary vasodilation following exogenous nitrates, using magnetic resonance angiography (MRA). The assessment of coronary response to exogenous nitrovasodilators may have a diagnostic and prognostic impact in patients with coronary artery disease. To date, stress imaging of coronary artery vasomotion has been confined to the catheterization laboratory. MRA is emerging as a noninvasive tool for coronary artery imaging. Coronary MRA was performed in 20 healthy volunteers (12 males, age = 33 +/- 8). We used spiral spoiled gradient echo (SSGE) sequences for imaging of coronary artery lumen. After the baseline short-axis view of the coronary artery was obtained, sublingual nitroglycerin (NTG) (0.3 mg) was administered. In all subjects, short-axis views of the coronary artery were acquired repetitively (8-10 times) from 1 up to 10 minutes after NTG administration. Measurements were obtained by two independent investigators. Interpretable short-axis view of left anterior descending artery (LAD) was obtained in 15 subjects (75%); in the remaining five subjects the right coronary artery (RCA) was examined. The interobserver variability was 15%, and the intraobserver variability 4%. The NTG-induced maximal vasodilation was 43 +/- 22%. The vasodilator response over time after NTG was maximal on average at 279 +/- 112 seconds, but with substantial heterogeneity. Entity and time course of nitrate-induced coronary vasodilation in the left anterior descending and/or RCA can be assessed using MRA with high feasibility and reproducibility. Coronary MRA has potential for dynamic imaging of coronary vasomotion.

Chronic Inflammation and Impaired Coronary Vasoreactivity in Patients With Coronary Risk Factors

The goal of this study was to examine a possible association between systemic microinflammation, as reflected by C-reactive protein (CRP) serum levels, and coronary vasomotion in patients with coronary risk factors but with angiographically normal coronary arteries. Coronary vasomotor function was studied in response to cold pressor testing (CPT) in 71 patients with normal angiograms. In all patients, CPT-induced changes in epicardial luminal area (LA; mm2) were assessed with quantitative angiography. Within 20 days, myocardial blood flow (MBF) responses to CPT were measured (mL x g(-1) x min(-1)) noninvasively with 13N-ammonia and PET imaging. The CPT-induced mean changes in LA and in MBF in patients with elevated CRP (> or =0.5 mg/dL) were significantly impaired compared with patients presenting with CRP levels within normal range (<0.5 mg/dL) (DeltaLA, -1.09+/-0.86 versus 0.45+/-0.63 mm2; DeltaMBF, 0.06+/-0.18 versus 0.44+/-0.31 mL x g(-1) x min(-1); P<0.0001, respectively). Coronary LA changes and MBF responses to CPT were inversely correlated with CRP serum levels (r=-0.84 and r=-0.63; P<0.0001). Lastly, regression analysis revealed a significant correlation between the changes in LA and MBF during CPT for patients with elevated CRP levels and those for patients with normal CRP levels (r=0.56 and r=0.66; P<0.001). These findings suggest a direct association between systemic microinflammation and altered coronary vasomotor function of both the epicardial conductance and the arteriolar resistance vessels.

Plasma level of oxidized low-density lipoprotein is an independent determinant of coronary macrovasomotor and microvasomotor responses induced by bradykinin

ObjectivesWe examined the relationship between coronary endothelium-dependent vasodilation in response to bradykinin (BK) and plasma levels of oxidized low-density lipoprotein (oxLDL) in subjects with normal coronary arteries. BackgroundIt is unclear whether the plasma oxLDL level is a determinant of coronary endothelial function. Bradykinin plays an important role in regulating resting coronary tone and flow-mediated coronary vasomotion. MethodsCoronary blood flow (CBF) in the left anterior descending (LAD) coronary artery was assessed by quantitative angiography and a Doppler flow wire in 94 consecutive subjects with normal coronary arteries. The plasma oxLDL level was measured by enzyme-linked immunosorbent assay using DLH3R, a specific antibody against oxLDL. ResultsPlasma levels of oxLDL in diabetic subjects (n = 13) were higher than those in non-diabetic subjects (n = 81). Plasma levels of oxLDL correlated with body mass index (BMI). Bradykinin at doses of 0.2, 0.6, and 2.0 μg/min caused dose-dependent increases in diameter and CBF in the LAD coronary artery. By a univariate analysis, oxLDL levels significantly correlated with epicardial (r = −0.30, p < 0.0001) and resistant (r = −0.36, p = 0.003) coronary vasodilator responses to BK at 2.0 μg/min, whereas total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides were not associated with these coronary responses. In a stepwise multivariate analysis, oxLDL levels were significantly correlated with epicardial and resistant coronary vasomotor responses to BK, independent of age, gender, smoking status, other lipid levels, BMI, hypertension, and diabetes. ConclusionsThe plasma level of oxLDL is an appropriate surrogate for assessing coronary endothelial-dependent vasomotor function as estimated by responses to BK compared with conventional risk factors for atherosclerosis.

Abnormal coronary vasomotion as a prognostic indicator of cardiovascular events in women: Results from the National Heart, Lung, and Blood Institute–sponsored Women's Ischemia Syndrome Evaluation (WISE)

Abnormal coronary vasomotion as a prognostic indicator of cardiovascular events in women: Results from the National Heart, Lung, and Blood Institute–sponsored Women's Ischemia Syndrome Evaluation (WISE)

Abnormal coronary vasomotion as a prognostic indicator of cardiovascular events in women: results from the National Heart, Lung, and Blood Institute-Sponsored Women's Ischemia Syndrome Evaluation (WISE).

Coronary vascular dysfunction has been linked to atherosclerosis and adverse cardiovascular outcomes in men, but these relationships have not been firmly established in women. As part of the Women's Ischemia Syndrome Evaluation (WISE) sponsored by the National Heart, Lung, and Blood Institute, 163 women referred for clinically indicated coronary angiography underwent coronary reactivity assessment with quantitative coronary angiography and intracoronary Doppler flow before and after intracoronary administration of acetylcholine, adenosine, and nitroglycerin and were then followed up for clinical outcomes. History of hypertension was present in 61%, dyslipidemia in 54%, diabetes in 26%, and current tobacco use in 21% of women enrolled. Seventy-five percent had no or only mild epicardial coronary artery disease (CAD). Over a median follow-up of 48 months, events occurred in 58 women. On bivariate analysis, women with an event had significantly less change in coronary cross-sectional area (DeltaCSA) in response to acetylcholine (P=0.0006) and nitroglycerin (P=0.04). In addition, women with abnormal coronary dilator response to acetylcholine had less time free from cardiovascular events (P=0.004). In multivariable analysis, after controlling for age, hypertension, diabetes, dyslipidemia, tobacco use, and CAD severity, %DeltaCSA with acetylcholine (P=0.001) independently predicted events. When the outcome was restricted to only death, myocardial infarction, congestive heart failure, and stroke, %DeltaCSA with acetylcholine remained a significant predictor (P=0.006). In women in this study, impaired coronary vasomotor response to acetylcholine was independently linked to adverse cardiovascular outcomes regardless of CAD severity.

Correlation of angiographic morphology immediately after coronary balloon angioplasty with coronary vasomotion late after angioplasty

Background: Various vasomotor responses to acetylcholine have been observed after coronary angioplasty. However, the relationship between the grade of vascular injury due to balloon angioplasty and vasomotor response to acetylcholine in the chronic stage is unknown. In this study we examined the correlation between the morphology immediately after coronary angioplasty and the vasomotor response to acetylcholine 1 year after angioplasty. Methods: Thirty nine patients with a total of 45 coronary lesions without restenosis 1 year after angioplasty were studied. The 45 lesions were divided into two groups according to the morphology immediately after angioplasty. Group A comprised smooth-walled dilation and smooth-walled dilation with intraluminal haziness which were considered to be related to injury limited to the intima or the surface of the media. Group B comprised intraluminal and extraluminal haziness and extraluminal type dissection which were considered to be related to extensive medial injury. In the 39 patients, acetylcholine provocation test was performed. Results: Transient total occlusion of angioplasty site was induced by acetylcholine in four lesions only in Group A. Percent change in coronary diameter after acetylcholine injection relative to that after injection of isosorbide dinitrate at the angioplasty site was larger in Group A than that of Group B. Conclusion: In the chronic stage, vessels with minor vascular injury exhibited a large vasomotor response to acetylcholine; conversely, the response was low in vessels with severe vascular injury by angioplasty. These observations suggest that severe vascular injury by balloon angioplasty may control coronary vasomotion in the chronic stage.

Effects of intravenous dobutamineon coronary vasomotion in humans

ObjectivesWe sought to investigate the vascular mechanisms of dobutamine-induced myocardial ischemia. BackgroundDobutamine stress is often used as a surrogate for exercise. The effects of dobutamine on the epicardial arteries are incompletely understood and possibly different from those of physical exercise. MethodsIntravenous (IV) dobutamine (40 μg/kg per min) was administered in 19 patients with normal, 23 patients with mildly atherosclerotic, and 12 patients with stenotic coronary arteries. In another two groups of patients with stenotic arteries, IV dobutamine was preceded by 1) an intracoronary (IC) bolus of the alpha-adrenergic blocker phentolamine (12 μg/kg, n = 12); and 2) an IC infusion of the nitric oxide substrate l-arginine (150 μmol/l per min for 20 min, n = 11). Intravenous saline instead of dobutamine was infused into eight patients with normal arteries. After dobutamine (or saline), an IC bolus of isosorbide dinitrate (ISDN, 0.2 mg) was given. Coronary vasomotion was evaluated by quantitative coronary angiography on angiograms obtained after each dose of dobutamine, saline, phentolamine, l-arginine, and ISDN. ResultsDobutamine increased the rate–pressure product and heart rate similarly in all patients except those who received saline. Dobutamine induced vasodilation in normal (change in luminal diameter [ΔLD] vs. baseline: 19 ± 2%) and in mildly atherosclerotic arteries (ΔLD: 8 ± 2%, p < 0.05 vs. normal). In stenotic arteries, dobutamine did not induce significant vasomotion (ΔLD: −3 ± 3%); the latter was improved by l-arginine (ΔLD: 10 ± 3%, p < 0.05 vs. stenotic arteries) and fully restored by phentolamine (ΔLD: 19 ± 3%, p < 0.05 vs. stenotic arteries). ConclusionsEndothelial dysfunction and enhanced alpha-adrenergic tone contribute to the loss of dobutamine-induced vasodilation in coronary atherosclerosis. In contrast to physical exercise, dobutamine does not induce “paradoxical vasoconstriction” of atherosclerotic coronary arteries.

Testing endothelial vasomotor function: nitric oxide, a multipotent molecule.

The initial description in 1980 by Furchgott and Zawadzki1 of endothelium-derived vasodilator factor has stimulated more than 2 decades of intense research to delineate the basic biology of the endothelium and its importance in the clinical setting.2 Endothelium-derived vasodilator factor has been identified as nitric oxide (NO).2 It is formed in endothelial cells from the amino acid l-arginine by endothelial isoform of NO synthase (eNOS), which is the product of the NOS3 gene.2,3 In addition to producing NO constitutively, the enzyme may be stimulated to increase NO synthesis by a variety of physiological agonists, shear stress, and pharmacological agents. Although discovered as a vasodilator, NO mediates many of the protective functions of the endothelium.4 It limits vascular recruitment of leukocytes by inhibiting the expression of proinflammatory cytokines, chemokines, and leukocyte adhesion molecules.2,4 It inhibits vascular smooth muscle proliferation and platelet adhesion and aggregation.2,4 NO also inhibits the production of tissue factor, a molecule that plays a critical role in the propensity of disrupted atherosclerotic plaques to cause intravascular thrombosis.5 In the setting of risk factors and experimental atherosclerosis, loss of the biological activity of endothelium-derived NO is accompanied by other alterations in endothelial phenotype that further increase the propensity for vasoconstriction, thrombosis, inflammation, and cellular proliferation in the vascular wall.6 Thus, endothelial dysfunction has the potential to contribute to key events in the course of human atherosclerosis. The experimental observations of Furchgott and others have stimulated translational research to elucidate the importance of endothelium-dependent vasodilation in human coronary atherosclerosis. Accordingly, Ludmer and colleagues7 administered the endothelium-dependent dilator acetylcholine into the coronary arteries of subjects undergoing cardiac catheterization. Acetylcholine induced dilation of normal epicardial coronary arteries but induced abnormal vasoconstriction, indicative of endothelial dysfunction, in patients with angiographic evidence of …

Rapid Effect of 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Inhibition on Coronary Endothelial Function

Treatment with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) decreases cardiovascular event rates in hypercholesterolemic patients. Whether statins exert effects within 24 hours on the coronary vasculature in patients with endothelial dysfunction has not been elucidated. Twenty-seven patients with stable angina pectoris and average low-density lipoprotein cholesterol concentrations of 138+/-9 mg/dL at baseline were allocated to treatment with placebo (14 patients) or 40 mg/d pravastatin (13 patients) in a randomized, double-blind, prospective trial. Coronary endothelial function was assessed before and 24 hours after single treatment by quantitative coronary angiography during intracoronary infusion of nitroglycerin or increasing concentrations of acetylcholine (0.01, 0.1, and 1 micromol/L). Coronary blood flow reserve was measured by Doppler velocimetry during adenosine infusion. Intracoronary acetylcholine infusion induced abnormal vasoconstriction in both groups before treatment, indicating coronary endothelial dysfunction. Treatment with a single oral 40-mg dose of pravastatin significantly attenuated acetylcholine-mediated vasoconstriction after 24 hours (mean+/-SE decrease in luminal diameter before and after treatment: 0.01 micromol/L, 6.1+/-2.2% versus 3.0+/-1.2%; 0.1 micromol/L, 15.6+/-2.6% versus 7.4+/-1.8%; P<0.05; 1 micromol/L, 22.9+/-2.9% versus 13.2+/-2.6%; P<0.05). There was no significant difference in the response to acetylcholine in the placebo group (8.1+/-2.4% versus 9.7+/-2.4%, 16.1+/-2.9% versus 16.8+/-3.2%, and 21.4+/-3.9% versus 23.3+/-4.2%). The response to nitroglycerin infusion was not altered in both groups. Increase in coronary blood flow in response to adenosine and coronary flow reserve remained unchanged during placebo and statin treatment. Serum concentrations of blood lipids and high-sensitive C-reactive protein were not significantly altered after 24 hours in response to placebo or pravastatin therapy. Statin treatment improves endothelium-dependent coronary vasomotion within 24 hours in the absence of significant cholesterol reduction. The full text of this article is available online at http://www.circresaha.org.

Absence of Kir6.1/KCNJ8 mutations in Italian patients with abnormal coronary vasomotion

The disturbances in coronary vasomotor tone have been extensively analyzed, but the exact molecular mechanisms underlying abnormal coronary vasomotion remain to be elucidated. It has been suggested that impaired coronary vasoreactivity can be the expression of a defect in vascular smooth muscle cells. A mouse model of human variant (vasospastic) angina has been recently obtained by disruption of Kir6.1/Kcnj8, a gene coding for a small pore-forming inward rectifier potassium channel. A phenotype resembling variant angina was also reported in mice lacking Sur2, the partner protein of Kir6.1. To better define the role of the smooth muscular ATP-sensitive potassium channels in the pathogenesis of abnormal coronary vasomotion, a complete mutational analysis of Kir6.1/KCNJ8 gene was performed in a series of 18 Italian patients with impaired coronary vasomotility. Polymerase chain reaction and direct sequencing of PCR products were done. No mutations were detected in the sample analyzed, thus suggesting that Kir6.1/KCNJ8 aberrations are not a common cause of abnormal coronary vasomotion in Italians. To the best of our knowledge, this study represents the first mutational analysis of Kir6.1/KCNJ8 gene in humans. Since major racial differences in the prevalence of abnormal coronary vasomotion have been described, further mutation screenings of Kir6.1/KCNJ8 gene are required to assess its role in the pathogenesis of impaired coronary vasomotility among various ethnic groups.

Vasomotor effects of iodinated contrast media: just side effects?

Routinely used iodinated contrast media have complex vasomotor effects on several arterial districts. All classes of iodinated radiographic contrast media are vasoactive, with iso-osmolar dimers inducing the smallest changes in vascular tone. The mechanisms responsible for contrast-induced vasomotor changes are not fully elucidated and are likely to be multifactorial. Although contrast-induced vasomotility is usually considered as an unwanted "side effect", recent findings suggest that it might indeed be useful in exploring the functional integrity of the vessel wall. We found that atherosclerosis has an impact on the type of the contrast-induced coronary vasomotor reaction. In fact, angiographically normal coronary segments show divergent vasomotor reactions to iodixanol or iopromide according to the presence/absence of, and distance from, a coronary atherosclerotic lesion located in their proximity. The mechanism responsible for this vasomotor effect does not apparently involve flow-mediated vasodilatation or endothelial nitric oxide synthesis. On the other hand, a cyclooxygenase product may be, at least in part, responsible for the vasodilating effect of non-ionic agents on epicardial coronary arteries, since contrast-induced vasodilatation is strongly inhibited in the presence of indomethacin. These findings have potential clinical implications, since the analysis of contrast-induced coronary vasomotion might result in a new test capable of evaluating vascular functional integrity. Such a test might be alternative or complementary to the tests based on muscarinic agonists (acetylcholine) or serotonin, which are known to evaluate the nitric oxide pathway.

Coronary vasoregulation in patients with various risk factors in response to cold pressor testing: Contrasting myocardial blood flow responses to short- and long-term vitamin C administration

ObjectivesWe sought to determine whether abnormal myocardial blood flow (MBF) responses to the cold pressor test (CPT) in patients with various risk factors may involve different mechanisms that could lead to varying responses of short- and long-term administration of antioxidants. BackgroundThere is a growing body of evidence that increased vascular production of reactive oxygen species markedly reduces the bioavailability of endothelium-derived nitric oxide, leading to impaired vasodilator function. It is unknown whether increased oxidative stress is the prevalent mechanism underlying endothelial dysfunction in patients with different coronary risk factors. MethodsFifty patients with normal coronary angiograms were studied. The MBF responses to CPT was determined by means of positron emission tomography before and after intravenous infusion of 3 g vitamin C or saline (placebo), as well as after 3 months and 2 years of 2 g vitamin C or placebo supplementation daily. ResultsIn hypertensive patients, the change in MBF (ΔMBF) was not modified significantly by short-term vitamin C administration challenges (0.20 ± 0.20 ml/g/min; p = NS) but was significantly increased after three months and two years of treatment with vitamin C versus baseline (0.58 ± 0.27 and 0.63 ± 0.17 vs. 0.14 ± 0.18 ml/g/min; both p ≤ 0.001). In smokers, ΔMBF in response to CPT was significantly increased after short-term vitamin C infusion and long-term vitamin C treatment (0.52 ± 0.10, 0.54 ± 0.13, 0.50 ± 0.07 vs. −0.08 ± 0.10 ml/g/min; all p ≤ 0.001). In hypercholesterolemic patients, no improvement in ΔMBF during CPT was observed after short- and long-term vitamin C treatment (0.05 ± 0.14, 0.08 ± 0.18, 0.02 ± 0.19 vs. 0.08 ± 0.16 ml/g/min; p = NS). The CPT-induced ΔMBF in hypertensive patients and smokers after follow-up was significant as compared with placebo and control subjects (p ≤ 0.001). ConclusionsThe present study revealed marked heterogeneous responses in MBF changes to short- and long-term vitamin C treatment in patients with various risk factors, which highlights the quite complex nature underlying abnormal coronary vasomotion.

Diadenosine polyphosphates: postulated mechanisms mediating the cardiac effects.

Diadenosine polyphosphates (Ap(n)A) are naturally occurring molecules which have been identified in human and guinea-pig cardiac tissue and whose physiological role is being established. They are stored in platelet dense granules in a metabolically inactive form. Ap(n)A form a class of dinucleotides, including diadenosine triphosphate (Ap3A), diadenosine tetraphosphate (Ap4A), diadenosine pentaphosphate (Ap5A) and diadenosine hexaphosphate (Ap6A) which have vasopressor actions in some tissues and vasodilator actions in others. Ap(n)A have been reported to interact with receptors distinct from P1 and P2-purinoceptors, and the presence of a unique Ap4A receptor has been demonstrated in isolated ventricular myocytes. Despite the identification of this receptor, other studies suggest that some of the cardiovascular effects are mediated by purinoceptors. Ap(n)A are released from platelet dense granules into the circulation during the platelet release reaction where they can reduce heart rate. The existence of Ap(n)A in myocardial tissue and platelet granules as well as their effects on coronary artery tone and myocardial function suggests a regulatory role for these compounds in the heart. This review describes the effects of Ap(n)A in terms of their coronary vasomotor and cardiac electrophysiological effects. The mechanism responsible for these effects is reviewed; including the involvement of purinergic receptors, the effects of alterations in extracellular pH and the contribution of nitric oxide and prostanoids. Potential pro-arrhythmogenic effects of diadenosine polyphosphates during myocardial ischaemia are also discussed as these compounds could contribute to inhomogeneities of repolarization in ischaemic myocardium.

Cigarette smoking and coronary blood flow

Cigarette smoking is associated with an increased risk for vascular disease. The effects of smoking and nicotine on coronary and peripheral arterial function have been probed with various invasive and noninvasive techniques. The current review provides a brief summary of the available techniques for measuring coronary or peripheral arterial function and discusses the determinants of myocardial blood flow at rest and during stress. Finally, it summarizes research addressing the effects of smoking on coronary and peripheral arterial function. Acute and chronic smoking does not appear to alter substantially endothelium independent coronary vasodilatory capacity. In contrast, active and passive smoking alters coronary and peripheral arterial vasomotion in patients with and individuals without coronary artery disease (CAD). Therefore, the site of the damaging effects of smoking appears to be the coronary endothelium. The smoking history is correlated with the degree of vasomotor abnormalities. Further, the degree of smoking-induced endothelial dysfunction appears to increase with the severity of CAD. Finally, the coronary endothelial and peripheral arterial vasomotor dysfunction observed in active and passive healthy smokers appear to be to some degree reversible. Copyright 2003, Elsevier Science (USA). All rights reserved.

745 Coronary vasomotion during dobutamine stress testing in patients with coronary artery disease

745 Coronary vasomotion during dobutamine stress testing in patients with coronary artery disease

Home-based versus hospital-based exercise programs in patients with coronary artery disease: Effects on coronary vasomotion

Background In a randomized study, we recently documented that a vigorous, hospital-based exercise training (ET) program improves coronary endothelial function in coronary artery disease. The aim of this consecutive study was to assess whether a home-based exercise program with reduced average training duration can sustain previously achieved effects on coronary endothelial function. Methods Nineteen patients with coronary endothelial dysfunction documented by acetylcholine-induced vasoconstriction were randomly assigned to a training group (n = 10) or a control group (n = 9). After 4 weeks of inhospital training (60 min of bicycle ergometry per day), all training patients were enrolled in a 5-month home-based program of 20 minutes' ergometry training per day and 1 group training session per week. At baseline, after 4 weeks and 6 months, endothelium-mediated vasodilation was assessed by quantitative coronary angiography after intracoronary infusions of acetylcholine. Average peak velocity (APV) was measured with a Doppler wire. Coronary blood flow (CBF) was calculated by multiplying vascular cross-sectional area and APV. Results CBF increased in response to 7.2 μg/min acetylcholine, from 27% ± 11% at the beginning of the study to 110% ± 24% after 4 weeks ( P < .01 vs control group). After 6 months, the increase in CBF was lower versus inhospital training (67% ± 18%, P < .05 vs 4 weeks). Changes in APV between 1 and 6 months correlated with daily training durations ( r = 0.65, P = .03). Conclusions Home-based ET sustained part of the effects of hospital-based ET on endothelium-dependent vasodilation in coronary artery disease. However, acetylcholine-induced increases in CBF were lower after home-based ET, suggesting a relation between daily training duration and improvement of coronary vasomotion. (Am Heart J 2003;145:e3.)

Angiotensin Converting Enzyme and Angiotensin II Type 1 Receptor Polymorphisms in Patients with Coronary Aneurysms

BackgroundConflicting results have been reported regarding the association of gene polymorphisms in the renin-angiotensin system (RAS) with different aspects of coronary artery disease (CAD), such as myocardial infarction, neointimal hyperplasia or coronary artery vasomotion. Since previous studies have linked angiotensin II to aneurysmal disease, our study hypothesis was that RAS gene polymorphisms may be associated with aneurysm remodeling in response to CAD.MethodsThe study population was selected from a series of 3862 consecutive patients who underwent coronary angiography in our institution. One hundred and thirteen consecutive patients with at least one coronary aneurysm (CA) were compared to 226 randomized control patients without CA. DNA was extracted from white blood cells. The angiotensin-converting enzyme (ACE) I/D and angiotensin type 1 receptor (AT1-R) A/C polymorphisms were detected using previously published techniques.ResultsThe distributions of the three ACE genotypes were similar in both groups: CA: 13%, 46%, and 41% for II, ID, and DD respectively; controls: 18%, 41%, and 41% for II, ID, and DD respectively, p = 0.45. The distributions of the three AT1-R genotypes were also similar in both groups: CA: 54%, 41%, and 5% for AA, AC, and CC respectively; controls: 55%, 33%, and 12%, for AA, AC, and CC respectively, p = 0.08.ConclusionOur results provide further information on the role of RAS polymorphisms on specific mechanisms implicated in CAD. Although an activated RAS may theoretically promote aneurysm formation, the 2 RAS polymorphisms analyzed in this study are not associated with this process in coronary arteries.

Cardiovascular effects of androgens.

In the process of atherosclerosis sex steroids play a complex role in the vascular vessel wall system. Although a number of experimental studies have clearly documented an atheroprotective effect of estrogens, in recent clinical studies, estrogen replacement therapy has failed to reduce cardiovascular mortality. The effects of androgens on the cardiovascular system and cardiovascular diseases are even more controversial. Whereas in the past, androgens were mainly believed to exert adverse effects on the cardiovascular system, recent studies in men have documented a number of beneficial actions of testosterone in the arterial vascular system. Androgens affect lipid metabolism (e.g., LDL and HDL cholesterol, Lp(a)) and hemostasis (e.g., platelet aggregation and fibrinolytic activity). In addition, several other physiological and pathophysiological processes in the arterial vessel wall are influenced by androgens. Acute hemodynamic effects of testosterone on coronary vasomotion and stress-test-induced ischemia were reported. Additionally, recent animal and in vitro studies have further documented an inhibitory effect of androgens on neointimal plaque formation. This review discusses different and, in part, contradictory effects of androgens on the cardiovascular system including potential signal transduction pathways in androgen target cells.

Blockade of angiotensin II type 1 receptors suppressed free radical production and preserved coronary endothelial function in the rabbit heart after myocardial infarction.

The hypothesis that blockade of angiotensin II type 1 (AT1) receptors after myocardial infarction prevents coronary endothelial vasomotor dysfunction by suppressing oxygen free radical production was examined. Rabbits underwent coronary ligation or a sham operation with or without infusion of valsartan, an AT 1 receptor blocker. Two weeks after the operation, the heart was isolated from each rabbit and perfused with buffer in the Langendorff mode, and coronary flow responses to acetylcholine and sodium nitroprusside were assessed. The ratio of heart weight to body weight and the lipid peroxide level in the myocardium were increased by 30 and 50%, respectively, 2 weeks after infarction. The coronary flow response to acetylcholine (10(-8) to 10(-5) M) was reduced by 50% in the hearts with infarction compared with the sham controls, although coronary flow responses to sodium nitroprusside were similar. The coronary flow response to acetylcholine in the hearts with infarction was restored by concurrent infusion of N -2-mercaptopropionyl-glycine, a free radical scavenger. Valsartan (10 mg/kg/d) infused after infarction prevented both ventricular remodeling and elevation of the tissue lipid peroxide level and preserved coronary flow response to acetylcholine. In conclusion, long-term AT1 receptor blockade after infarction protects the coronary arteries from endothelial vasomotor dysfunction through suppression of free radical production.

Decrease in coronary blood flow reserve during hyperlipidemia is secondary to an increase in blood viscosity.

During maximal hyperemia, capillaries provide the greatest resistance to flow. A major determinant of capillary resistance is viscosity. We, therefore, hypothesized that abnormal coronary blood flow (CBF) reserve observed during hyperlipidemia is secondary to increased blood viscosity and not abnormal coronary vasomotion. Maximal hyperemia was induced in 9 dogs using adenosine. Serum triglyceride levels were increased by incremental doses of Intralipid. A good correlation was noted between serum triglyceride levels and blood viscosity (r=0.82). Neither total coronary blood volume nor myocardial blood volume changed with increasing serum triglyceride levels, indicating lack of vasomotion. Myocardial vascular resistance (MVR) increased with increasing triglyceride levels (r=0.84), while hyperemic myocardial blood flow (MBF) decreased (r=-0.64). The decrease in hyperemic MBF was associated with a decrease in blood velocity (r=-0.56). These findings were confirmed with direct intravital microscopic observations in the mice cremaster muscle. Increasing lipid levels in a fully dilated normal coronary bed causes no change in large or small vessel dimensions. Instead, the increase in blood viscosity causes capillary resistance to rise, which attenuates hyperemic CBF. Therefore, the abnormal CBF reserve associated with hyperlipidemia is due to increase blood viscosity and not abnormal vascular function.