肱动脉血流介导的舒张功能与冠心病的相关性

目的：探讨超声评价肱动脉的直径与血流介导的舒张功能与冠心病的关系。方法：依据冠状动脉造影结果将47例胸痛患者分为3组：正常对照组16例（冠状动脉造影阴性），冠心病A组12例（冠状动脉管腔内径减少小于50％），冠心病B组19例（至少一支冠脉狭窄管腔减少大于50％）。超声检测每组受试者肱动脉的基础内径以及血流介导的舒张功能（FMD）。结果：冠心病B组肱动脉内径大于对照组（P〈0．01），冠心病组FMD均明显低于正常对照组（P〈0．01）。所有受试者肱动脉的FMD与基础内径呈负相关（P〈0．05）。结论：肱动脉FMD与冠心病关系密切，应用高分辨率超声检测肱动脉的内径及FMD，对无创性诊断冠心病具有一定的临床意义。     

Restoration of flow-dependent coronary dilation by ACE inhibition improves papaverine-induced maximal coronary blood flow in hypertensive patients: demonstration that large epicardial coronary arteries are more than conductance vessels

Restoration of flow-dependent coronary artery dilation by angiotensin-converting enzyme inhibition (ACEI) has been demonstrated in patients with hypertension. The aim of the present study was to evaluate whether dilation of conductance coronary arteries may alter maximal coronary blood flow (CBFmax) and minimal coronary resistance (CRmin) in hypertensive patients with reversible impairment of flow-dependent coronary artery dilation. Thirteen hypertensive patients with angiographically normal coronary arteries and no other risk factors were studied. Cross-sectional areas (CSAs) of proximal and distal left anterior descending (LAD) coronary arteries were determined by quantitative angiography. Coronary flow velocity was recorded in the distal LAD with an intracoronary Doppler catheter. Estimates of coronary blood flow and resistance were calculated at rest and during maximal increase in blood flow induced by papaverine injected in the midportion of the LAD, both before and after ACEI. Flow-dependent dilation of the proximal LAD, abolished before ACEI, was restored after (26.7 +/- 11.2%; p < 0.001). The increase in CSA of the distal LAD exposed to papaverine was significantly higher after ACEI than before (from 33.4 +/- 20.5% to 51.5 +/- 23.4%; p < 0.001). After restoration of proximal LAD flow-dependent dilation, CBFmax was increased by +21.0 +/- 10.3% (p < 0.001), and CRmin was reduced by 19.3 +/- 9.5% (p < 0.001). Thus, dilation of epicardial coronary arteries participates substantially in the coronary resistance in hypertensive patients. Restoration of flow-dependent coronary artery dilation by ACEI may improve the ability of coronary circulation to deliver its maximal myocardial blood flow in hypertensive patients.     

The relationship between flow-mediated brachial artery vasodilation and coronary vasomotor responses to bradykinin: comparison with those to acetylcholine

Flow-mediated dilation (FMD) of brachial artery provides a noninvasive assessment of coronary endothelial dysfunction. Acetylcholine (ACh) has been used as an agent for estimating coronary endothelial function. In contrast to ACh, there is no evidence for a relationship between FMD and coronary vasodilation to bradykinin (BK). The aim of this study was to compare the flow-mediated vasodilation of brachial artery with coronary vasomotor responses to intracoronary ACh or BK in patients with an angiographically normal left anterior descending coronary artery. Ninety-one patients underwent the cardiac catheterization examination with coronary endothelial function testing and the brachial ultrasound study. BK (0.2, 0.6, 2.0 microg/min) and ACh (3, 10, 30 microg/min) were administered into the left coronary artery in a stepwise manner. Coronary blood flow was evaluated by the Doppler flow velocity measurement. Coronary diameters were measured by the quantitative coronary angiography. The assessment of endothelial function in the brachial artery was made in response to reactive hyperemia with high-resolution ultrasound. Bradykinin induced dose-dependent increases in epicardial coronary diameter and blood flow. There was a significant positive correlation between FMD- and BK-induced vasodilations of epicardial coronary arteries (0.2 microg/min: r = 0.30; 0.6 microg/min: r = 0.42; 2.0 microg/min: r = 0.44, P < 0.01, respectively) and resistance coronary arteries (0.2 microg/min: r = 0.40; 0.6 microg/min: r = 0.56; 2.0 microg/min: r = 0.59, P < 0.0001, respectively). FMD correlated with ACh-induced vasomotions of resistance but not epicardial coronary arteries. No correlation was seen between nitroglycerin-induced brachial artery vasodilation and BK-induced coronary vasodilation. The endothelial dysfunction of peripheral arteries correlated well with that of the coronary arteries especially vasomotor responses to BK.     

Molsidomine improves flow-dependent vasodilation in brachial arteries of patients with coronary artery disease

Flow-mediated vasodilation (FMD) of human blood vessels is essential to adaptation and regulation of peripheral blood flow, and is mediated by endogenously produced nitric oxide. Endothelial function is impaired in many pathologic states, especially in coronary heart disease. We questioned in this study whether exogenous nitric oxide (NO) would restore endothelial dysfunction in peripheral arteries of patients with coronary artery disease (CAD). In a randomized double-blinded case-control assay, we used computerized A-mode ultrasonography to measure diastolic diameters of the brachial artery before and after hyperemia in two groups of 10 patients with CAD. Each group received orally either placebo or 12 mg molsidomine a day for 48 h. In the molsidomine group, FMD was improved with a 60% increase after the first intake of molsidomine, and the same trend was observed after the last intake, although less pronounced. Significant increase in diastolic diameter was observed after the last molsidomine intake, but not after the first one. Thus molsidomine has an early positive effect on FMD in addition to a delayed vasodilator effect. Improvement of endothelial dysfunction by molsidomine in patients with CAD may uncover new therapeutic perceptive in the use of nitrovasodilators.     

Chronic decrease in flow contributes to heart failure-induced endothelial dysfunction in rats

Chronic heart failure (CHF) impairs endothelium-dependent, nitric oxide (NO)-mediated dilation. This decreased dilation may be partly secondary to the chronic decrease in blood flow, but this hypothesis has not yet been tested. Thus, we assessed whether a localized, chronic increase in blood flow in vivo reverses endothelial dysfunction of small arteries in rats with CHF. Two months after coronary artery ligation or sham surgery, second-order side branches of the superior mesenteric artery were ligated in order to obtain persistently elevated blood flow (HF) in the adjacent first-order side branch compared with normal vessels (NF). One month later, responses to acetylcholine and flow-mediated vasodilatation (FMD) were assessed in vitro in an arteriograph. Chronic heart failure induced a decrease in mesenteric blood flow (374 +/- 25 and 305 +/- 27 micro L/min for sham and CHF, respectively; P < 0.05). Neither CHF nor the chronic increase in flow affected the responses to acetylcholine. Chronic heart failure decreased FMD (maximal response in sham and control 34 +/- 6 and 13 +/- 4%, respectively; P < 0.05). Chronic increases in blood flow did not modify FMD in sham, but restored FMD in CHF rats (28 +/- 4%; P < 0.05 vs CHF NF). The restored response was abolished by an inhibitor of NO synthesis (N(G)-nitro-l-arginine). Chronic heart failure did not affect the abundance of mesenteric endothelial NO synthase (eNOS) mRNA. A chronic increase in flow significantly increased the abundance of eNOS mRNA in sham rats, but only moderately and non-significantly in CHF rats. Thus, endothelial dysfunction of small arteries in CHF appears to be largely the consequence of the chronic decrease in flow.     

Forearm endothelial response in smokeless tobacco users compared with cigarette smokers and nonusers of tobacco

STUDY OBJECTIVE: To compare brachial artery flow-mediated dilation (FMD) in subjects who use smokeless tobacco, smoke cigarettes, or do not use any tobacco product. DESIGN: Cross-sectional study. SETTING: University-affiliated outpatient clinic. SUBJECTS: Seventeen apparently healthy volunteers who for more than 1 year smoked at least 10 cigarettes/day, used at least two containers of smokeless tobacco/week, or did not use any tobacco product. MEASUREMENTS AND MAIN RESULTS: Baseline characteristics of subjects were similar among the three groups except for mean age and serum cotinine level. Baseline brachial artery diameter, endothelium-dependent FMD induced by reactive hyperemia, and endothelium-independent dilation induced by administration of sublingual nitroglycerin were measured. Mean FMD over baseline was 4.1% +/- 0.7% in subjects who used smokeless tobacco, 3.9% +/- 5.1% in cigarettes smokers, and 12.2% +/- 5.7% in nonusers of tobacco (p=0.01). Endothelium-independent dilation induced by nitroglycerin was not statistically different among the three groups. CONCLUSION: Brachial artery FMD, a surrogate for endothelial dysfunction, was significantly impaired in smokeless tobacco users and cigarette smokers compared with nonusers of tobacco.     

奥利司他对肥胖合并高血压患者内皮依赖性血管舒张功能的影响

目的 观察肥胖合并高血压患者服用奥利司他治疗前后血压和超声肱动脉内皮依赖性血管舒张功能的变化。方法 30例肥胖合并轻度高血压患者(肥胖高血压组)服用脂肪酶抑制剂——奥利司他120 mg,每日3次,共12周,服药前后诊所测量身高、体重、腰围及血压,并行肱动脉超声检查,测定血流介导的血管舒张功能(FMD)。15例非肥胖的高血压患者作为对照组。结果 肥胖高血压组治疗前加压反应性充血后肱动脉内径平均增加9.6％,增加幅度显著低于对照组(P<0.01);而奥利司他治疗12周后,加压反应性充血后肱动脉内径增加达14.2％、流速增加达56.7％,FMD较治疗前显著改善(均P<0.01)。肥胖高血压组患者治疗后平均减重5.3 kg,腰围减少6.3 cm,收缩压/舒张压平均下降13.3/5.7 mmHg(1mmHg=0.133kPa),与治疗前比较有显著性差异(均P<0.05)。结论 奥利司他能降低肥胖合并高血压患者的体重及收缩压和舒张压,并能改善血流介导的内皮依赖性动脉舒张功能。     

Is impaired flow-mediated dilatation of the brachial artery a cardiovascular risk factor?

Endothelial dysfunction is thought to be an important factor in the development of atherosclerosis. Over the past decade, a non-invasive technique has evolved to evaluate flow-mediated vasodilation ([FMD), an endothelium-dependent function, in the brachial artery. FMD decreases with increasing age and subjects with diabetes mellitus, hypercholesterolemia, smokers and hypertension have decreased FMD. There are a few concise studies reporting that FMD predicts cardiovascular events. However, the assumption that focal measurement of brachial artery FMD predicts coronary artery disease deserves further investigation.     

Continuous therapy with nitroglycerin impairs endothelium-dependent vasodilation but does not cause tolerance in conductance arteries: a human in vivo study

We investigated in healthy humans whether continuous therapy with organic nitrates impairs conduit artery responses to nitroglycerin (GTN) as well as its effects on endothelium-dependent vasodilation. Sixteen young male volunteers were randomized to continuous treatment with either transdermal GTN (0.6 mg/h/24 hrs for 6 days) or no therapy. Endothelium-dependent (flow-mediated) dilatation (FMD) and endothelium-independent (GTN-mediated) dilatation (GMD) of the brachial artery were evaluated before randomization (session 1), after six days of transdermal GTN treatment (session 2), and three hours after withdrawal of transdermal GTN (session 3). In the GTN group, on session 1, 0.4 mg sublingual GTN increased resting brachial artery diameter from 0.40 +/- 0.03 to 0.45 +/- 0.03 cm (P < 0.01). At the time of session 2, this GTN-mediated vasodilation remained unchanged at baseline (0.47 +/- 0.04 cm), with no further significant dilatation in response to either stimulus. On session 3, three hours after patch removal, baseline brachial artery diameter and GMD returned to pretreatment values, but FMD remained blunted (session 1: 8.7 +/- 2.5; session 3: 4.1 +/- 1.7%, P < 0.05). There was no change in these variables in the control group. Our data demonstrate that continuous GTN therapy impairs endothelium-dependent vasodilation in conduit arteries yet does not induce nitrate tolerance.     

Intracoronary collagen: effects on coronary collateral circulation and the role of thromboxane

This study investigated the effects of intravascular collagen on coronary collateral blood flow. Collateral vessel growth was stimulated in 11 dogs by embolizing the left anterior descending (LAD) coronary artery with a hollow stainless steel plug. Experiments were performed 41 +/- 7 days after coronary embolization when collateral vessels were moderately well developed. Under alpha-chloralose anesthesia, the LAD was cannulated, and retrograde blood flow was used as a measure of collateral flow. Collagen (10-100 microg/kg) injected into the left main coronary artery caused a decrease of coronary collateral blood flow that became maximal at 3 min after injection and subsided within 9 min. At peak effect intracoronary collagen decreased retrograde flow by 53 +/- 6% from 32.7 +/- 8.2 to 16.8 +/- 3.7 ml/min (p < 0.05) with no change in systemic hemodynamics. Selective thromboxane A2 (TxA2)-receptor blockade with SQ30,741 had no effect on collateral blood flow during basal conditions but attenuated the collateral constriction in response to collagen. Thus, after SQ30,741, collagen caused only a nonsignificant decrease retrograde flow from 35.9 +/- 9.0 to 31.7 +/- 9.62 ml/min. The findings indicate that intravascular collagen exerts a potent vasoconstrictor effect on coronary collateral vessels. Attenuation of this response by TxA2-receptor blockade suggests that thromboxane released by activated platelets is the principal mediator of this response.     

Improvement in endothelial dysfunction in patients with hypoalphalipoproteinemia and coronary artery disease treated with bezafibrate

Isolated low high-density lipoprotein cholesterol (HDLc) is a well-known risk factor for cardiovascular disease and is associated with arterial endothelium dysfunction. Several studies have shown that cholesterol lowering in patients with hypercholesterolemia improves endothelial function, but the effect of treating low HDLc levels remains unknown. We studied the effect of increasing HDLc on endothelial function in patients with coronary artery disease (CAD) and isolated low HDLc (HDLc) <0.91 mM, low-density lipoprotein cholesterol (LDLc) <4.1 mM, and triglycerides <2.8 mM. Flow-mediated endothelium-dependent dilatation (FMD) in response to reactive hyperemia was measured by brachial ultrasound, before and after bezafibrate treatment (400 mg daily for 6 months) in 16 patients with CAD and impaired FMD (<10%). After bezafibrate therapy, HDLc increased from 0.79-1.0 mM (p = 0.0008) at the expense of both HDL2 and HDL3 subfractions, apolipoprotein A-I increased from 1.04-1.19 g/l (p = 0.0012), and fibrinogen decreased from 4.45-3.39 g/l (p = 0.0007). The impaired FMD increased after bezafibrate treatment from a median of 2.5-12.3% (p = 0.0004). Endothelial function was normalized in eight patients (50%), improved in four (25%), and did not change in four (25%). These observations indicate that in patients with isolated low HDLc and CAD, bezafibrate treatment improves endothelial function of brachial arteries, increases HDLc and apolipoprotein A-I, and lowers fibrinogen concentrations.     

Perfusion with non-oxygenated Tyrode solution causes maximal coronary vasodilation in canine hearts

1. Coronary vasodilator effects of non-ischaemic hypoxia (perfusion with non-oxygenated Tyrode solution) and ischaemic hypoxia (coronary occlusion) were compared. 2. The left anterior descending coronary artery (LAD) of six in situ canine hearts was perfused selectively at controlled pressure with normal arterial blood or with non-oxygenated Tyrode solution. LAD flow was measured continuously with an electromagnetic flowmeter. Reactive hyperaemic blood flow responses following 3 min Tyrode perfusion were compared with responses following 3 min complete coronary occlusion. 3. Control LAD blood flow was 26.9 +/- 4.6 ml/min. A 3 min period of Tyrode perfusion caused a peak reactive hyperaemic blood flow of 151 +/- 31 ml/min, which was not significantly different from that caused by 3 min occlusion, 123 +/- 17 ml/min. The duration and total volume of reactive hyperaemia flow following Tyrode perfusion were smaller than values following occlusion. 4. The present findings demonstrate that myocardial hypoxia per se is a sufficient vasodilatory stimulus to account for the peak reactive hyperaemic flow following 3 min occlusion, but that the prolonged reactive hyperaemic response depends on vasodilator metabolites which accumulate in ischaemic myocardium.     

Influence of cinepazide, a vasoactive substance, on canine coronary circulation after acute constriction of the left anterior descending coronary artery.

The left anterior descending coronary artery was variably constricted mechanically in nine dogs. Blood flow in the left anterior descending (LAD) and circumflex coronary arteries (CCA), aortic pressure and peripheral, i.e. post-stenotic coronary pressure were measured. Myocardial perfusion was determined from the clearance of radioactive xenon injected at a depth of 7 mm into the underperfused area supplied by the LAD artery. The vasoactive drug 1-(pyrrolidinyl-1-carbonyl)-methyl-4-(3,4,5-tri-methoxycinnamoyl)piperazine-maleate (cinepazide) was given at doses of 5-10 mg/kg by i.v. route. 1. Blood flow in the LAD was decreased stepwise to 50% of its initial value. There was practically no more coronary reserve. After drug injection, diastolic aortic pressure, that normally falls, was kept constant by clamping. Heart rate, perfusion pressure, post-stenotic pressure, and blood flow and resistance in the LAD showed practically no change. In the CCA, blood flow increased significantly (p less than 0.005) and flow resistance decreased (p less than 0.001). 133Xe clearance showed an increased myocardial perfusion (p less than 0.02) in the territory supplied by the LAD artery. 2. The lumen of the LAD was narrowed by 53%, i.e., coronary reserve was decreased. This constriction was followed by no haemodynamic reaction. After injection of cinepazide, mean and diastolic aortic pressure (p less than 0.02) and post-stenotic coronary pressure (p less than 0.005) decreased. Blood flow increased by 41% in the CCA and by 31% in the LAD. Coronary resistance in these vessels decreased (p less than 0.001 and 0.005, respectively). Here, too, the 133Xe clearance curve showed an increase in myocardial perfusion in the territory supplied by the LAD artery (+78%).     

The acute effect of orlistat on endothelial function in young obese women

Recent studies indicate that abdominal fat accumulation is related to impaired endothelial function in young healthy volunteers. The aim of this study was to determine the acute effect of gastrointestinal lipase inhibitor on brachial flow-mediated vasodilatation and hemodynamic parameters in young obese women. The study population was composed of 42 female obese patients (mean age 29 +/- 4 years, age range between 18 and 34 years). Flow-mediated endothelial-dependent vasodilatation was assessed in the brachial artery in response to reactive hyperemia using high-resolution ultrasound. Brachial artery diameter (3.46 +/- 0.72 mm to 3.82 +/- 0.84 mm) and flow-mediated vasodilation (7.6 +/- 0.8% to 9.8 +/- 1.6%) changed significantly after 12 weeks of therapy (p < 0.001). Brachial artery flow was not changed (124 +/- 92 ml/min to 148 +/- 14 ml/min, p > 0.05). The results of this study demonstrate that orlistat improved endothelial function, weight, body mass index and systolic and diastolic blood pressure in young women.     

Systemic plasma levels of nitrite/nitrate (NOx) reflect brachial flow-mediated dilation responses in young men and women

1. The aim of the present study was to determine the relationship between plasma levels of nitrite/nitrite (NO(x)) and brachial flow-mediated dilation (FMD) in healthy young men and women. 2. Brachial artery FMD was assessed non-invasively using high-resolution ultrasound in 36 young men and women (21 +/- 3 years; 18 men and 18 women). Blood samples for NO(x) assays were collected from an indwelling venous catheter in the forearm following an overnight fast and a 36 h low-nitrate diet. 3. Plasma levels of NO(x) were related to peak brachial FMD% (r = 0.53; P = 0.001). The relationship was maintained when the brachial dilation was expressed as absolute diameter change (Deltamm; r = 0.51; P = 0.002) and when it was normalized (/s) to the mean shear rate (r = 0.50; P = 0.002). 4. The present study demonstrates a relationship between peak FMD in the brachial artery and plasma levels of NO(x) in young men and women. This relationship suggests that brachial FMD and/or plasma NO(x) may be used as markers of peripheral endothelial function.     

Vasodilator responses of coronary conduit and resistance arteries to continuous nitroglycerin infusion in humans: a Doppler guide wire study

To examine the responses of coronary conduit and resistance arteries to the continuous i.v. administration of nitroglycerin in 15 patients with atypical chest pain, we measured coronary blood flow velocity in the left anterior descending coronary artery using a Doppler guide wire and the lumen diameter and cross-sectional area by quantitative coronary angiography. Systolic flow, diastolic flow, total coronary flow, and coronary vascular resistance were calculated. Stepwise increases in dose of nitroglycerin resulted in significant dose-dependent decrease in mean aortic pressure (p < 0.01) and increase in lumen diameter (p < 0.05). After nitroglycerin administration of 0.5 microg/kg/min, systolic flow decreased significantly by 89.9+/-15.7% (p < 0.01), and diastolic flow increased significantly by 74.2+/-37.1% (p < 0.05). Total coronary flow did not change significantly with the various doses of nitroglycerin. However, coronary vascular resistance decreased significantly at concentrations greater than 0.5 microg/kg/min nitroglycerin. Continuous nitroglycerin infusion did not reduce either diastolic or total coronary blood flow despite a significant reduction in coronary perfusion pressure. These results indicate that subendocardial blood flow might be maintained during continuous i.v. infusion of nitroglycerin within the clinical dose range.     

氨氯地平对原发性高血压患者血管内皮功能及胰岛素抵抗的影响

目的探讨氨氯地平对原发性高血压患者内皮功能及胰岛素抵抗的影响。方法选择42例原发性高血压患者为治疗组,血压正常的健康人30例为对照组。治疗组口服氨氯地平8周,并在治疗前后采取静脉血测定空腹血糖及胰岛素,计算胰岛素敏感性指数（ISI）;采用血管外超声法检测治疗前后肱动脉内皮依赖性血管舒张功能（FDM）,并观察肱动脉内径基础值（D0）变化。结果治疗组治疗前收缩压、舒张压、空腹血糖、空腹胰岛素均明显高于对照组,且D0、ISI、FMD均低于对照组,差异均有统计学意义（P〈0.01）;治疗8周后患者收缩压、舒张压、空腹胰岛素水平降低,ISI升高,D0及血流介导的FDM明显改善,与治疗前比较差异均有统计学意义（P〈0.01）。结论氨氯地平在有效降压的同时,能改善原发性高血压患者胰岛素抵抗及肱动脉内皮依赖性血管舒张功能。     

中老年糖耐量减低患者早期动脉硬化的危险因素

目的:探讨影响中老年糖耐量减低(IGT)患者早期动脉硬化(AS)的危险因素.方法:选取中老年IGT患者(IGT组)及正常对照(NGT组)各50例,采用高分辨率多普勒超声检测2组颈动脉内-中膜厚度(IMT)值和肱动脉血流介导的血管扩张功能(FMD),用肱动脉舒张内径的变化率(D%)表示;检测身高、体质量、腰围、臀围、血压,测定空腹(FPG)及糖负荷后2 h血浆血糖(2 hPG)、空腹胰岛素(FINS)、三酰甘油(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、高敏C反应蛋白(hs-CRP)、一氧化氮(NO),并计算体质量指数(BMI)、腰臀比(WHR)、胰岛素抵抗指数(HOMA-IR).分析上述指标与颈动脉IMT的相关性及影响颈动脉IMT的危险因素.结果:IGT组BMI、WHR、2 hPG、TG、LDL-C、hs-CRP、HNS、HOMA-IR和颈动脉IMT均较NGT组增高,但NO及D%较NGT组减低,差别均有统计学意义(P＜0.05或P＜0.01);IGT组颈动脉IMT与年龄、BMI、WHR、2hPG、TC、LDL-C、ks-CRP及HOMA-IR均呈正相关(P＜0.05或P＜0.01),与D%呈负相关(P＜0.01);年龄、WHR、HOMA-IR及D%是颈动脉IMT的影响因素.结论:年龄、中心型肥胖、胰岛素抵抗、内皮功能异常是影响中老年IGT患者发生早期AS的因素.     

The effect of the carotid sinus reflex on large coronary artery diameter in anaesthetized dogs

1. The diameter of, and blood flow in, the left circumflex coronary artery was measured in anaesthetized dogs and the carotid sinus reflex was stimulated by bilateral occlusion of the carotid arteries (BCO) for 2 min. 2. The effect of BCO on coronary artery diameter and late diastolic coronary resistance was examined: (a) after bilateral vagotomy; (b) after vagotomy plus antagonism of beta-adrenoceptors with propranolol (1 mg/kg, i.v.); and (c) after vagotomy, antagonism of beta-adrenoceptors and antagonism of alpha-adrenoceptors with phentolamine (0.5 mg/kg, i.v.). 3. After vagotomy BCO increased mean arterial pressure (delta = 72 +/- 7 mmHg), heart rate (16 +/- 3 beats/min), coronary blood flow (37 +/- 11 ml/min) and coronary artery diameter (0.14 +/- 0.04 mm). Late diastolic coronary resistance initially fell (-0.26 +/- 0.13 mmHg min/ml at 30 s) but at the end of the 2 min occlusion it had returned to the baseline level (delta = 0.04 +/- 0.08 mmHg min/ml). 4. In the presence of propranolol BCO increased arterial pressure (28 +/- 12 mmHg), but did not alter heart rate (0.6 +/- 0.4 beats/min) or coronary blood flow (2 +/- 2 ml/min). There was a significant decrease in large artery diameter (-0.24 +/- 0.07 mm) and an increase in late diastolic coronary resistance (0.46 +/- 0.12 mmHg min/ml). A mechanical increase in afterload did not affect large coronary artery diameter or coronary resistance. 5. Antagonism of alpha-adrenoceptors abolished the reflex-induced constriction of the large coronary artery (delta = -0.02 +/- 0.02 mm) and the coronary resistance vessels (delta LDCR = -0.02 +/- 0.03 mmHg min ml).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of the long-term administration of nicorandil on vascular endothelial function and the progression of arteriosclerosis

This study compared the effects of long-term administration of nicorandil and isosorbide dinitrate (ISDN) on vascular endothelial function and the progression of arteriosclerosis. Forty-two patients with ischemic heart disease were randomly allocated to receive nicorandil (N group; 15 mg/d) or ISDN (I group, 40 mg/d). Twelve normal subjects served as controls. Vascular endothelial function and the progression of arteriosclerosis (intima-media thickness, IMT), as determined by carotid vascular ultrasound, were assessed 1 week before and 3 months after drug administration. Reactive hyperemia was induced in the forearm for 5 minutes, and the percentage change in the diameter of the brachial artery (% change in flow-mediated dilation, %FMD) was calculated. FMD was significantly lower in CAD groups than in controls. The %FMD significantly decreased (7.2 +/- 1.9 to 4.2 +/- 2.8) in the I group, while rising from 6.8 +/- 1.6 to 8.0 +/- 2.0 in the N group. IMT increased by 0.036 +/- 0.015 mm in the I group but showed no significant change in the N group (-0.01 +/- 0.012 mm). Thus, ISDN deteriorates IMT and FMD, whereas a beneficial effect of nicorandil is seen on FMD with no effect on IMT. Long-term treatment with nicorandil may be desirable for prevention of cardiovascular events.