Coronary Vasomotor Research Articles

Endothelin-1 is not involved in serotonin-induced coronary spasm in a swine model

The role of endothelin-1 (ET-1) in the pathogenesis of coronary artery spasm is not well understood. We aimed to determine if ET-1 is involved in serotonin-induced coronary spasm in the swine model. In 10 miniature pigs, a segment of the left anterior descending coronary artery was denuded and irradiated with X-ray. Three months after endothelial denudation, coronary vasomotion was assessed in vivo by quantitative arteriography. Intracoronary serotonin at 10 micrograms/kg provoked coronary spasm (augmented narrowing of the luminal diameter) at the denuded site (diameter reduction 93 +/- 4%) but not at the non-denuded control site (19 +/- 4%, P < 0.01) associated with ST segment elevation in the region perfused by the denuded artery. Intracoronary administration of ET-1 at 25 ng/kg caused mild vasoconstriction of the denuded (26 +/- 4) and non-denuded site (16 +/- 3%, n.s.), but provoked ST segment elevation in the regions perfused by both the denuded and non-denuded arteries. The treatment with an endothelin antagonist (BQ123 0.1 mg/kg) significantly attenuated coronary vasoconstriction and ST segment elevation evoked with ET-1, but did not alter serotonin-induced vasoconstriction either at the denuded or control site. The results of this study suggest that endogenous ET-1 may not be involved in the pathogenesis of serotonin-induced coronary spasm in our swine model.

Coronary artery response to cold-pressor test is impaired early after operation in heart transplant recipients

Objectives. The aim of the present study was to evaluate the coronary vasomotor response to the cold-pressor test within 3 months after heart transplantation.Background. Normal epicardial coronary arteries dilate in response to sympathetic stimulation evoked by the cold-pressor test. In transplant recipients, abnormal coronary vasomotion has been described shortly after operation.Methods. Fourteen heart transplant recipients were compared 52 ± 15 days (mean ± SD) after operation with 10 control subjects. All had angiographically normal epicardial coronary arteries. Coronary blood flow velocity was measured with a Doppler catheter placed in the proximal left anterior descending coronary artery. Four segments in each patient were analyzed by quantitative coronary angiography to assess the diameter changes during the cold-pressor test and after intracoronary injection of isosorbide dinitrate.Results. Coronary flow velocity increased similarly during the cold-pressor test in control subjects and in transplant recipients, from 7.5 ± 2.3 to 11.0 ± 3.9 cm/s and from 10.3 ± 3.2 to 13.7 ± 4.8 cm/s (both p < 0.01). In control subjects, 39 of 40 segments analyzed dilated during the cold-pressor test. In transplant recipients, 48 of 56 segments analyzed did not change or constricted. The mean epicardial coronary diameter increased significantly during the cold-pressor test in control subjects (+ 13 ± 6%, p < 0.001), whereas it did not change significantly in transplant recipients (−2 ± 9%, p = NS). In transplant recipients, isosorbide dinitrate elicited coronary vasodilation similar to that in control subjects.Conclusions. These data indicate that in human transplanted denervated hearts, coronary vasodilation in response to sympathetic stimulation by cold exposure is impaired shortly after operation.

Effects of L-arginine analogues on vasomotion of isolated porcine coronary arteries.

L-Arginine analogues have been widely used to examine the role of endothelium-derived nitric oxide (NO) in vascular responses; however, the effects of the agents on coronary vasomotion are not fully understood. In this study, we examined the effects of the analogues on vasomotion of isolated porcine coronary arteries. Strips of the porcine coronary artery were suspended for isometric tension recording in Krebs-Henseleit solution. L-Arginine analogues, N omega-nitro-L-arginine methyl ester (L-NAME, 10(-9)-10(-3) M), NG-monomethyl-L-arginine (L-NMMA, 10(-9)-10(-3) M), and NG-nitro-L-arginine (L-NNA, 10(-9)-10(-3) M), caused dose-dependent contractions, which were greater in strips with than in those without endothelium. Those endothelium-dependent contractions were almost abolished by indomethacin (10(-5) M) and FeCl2 (10(-3) M). The latter reduces prostaglandin H2 to 12-heptadecatrienoic acid, which has no vasoconstrictor effect. These results indicate that the L-arginine analogues cause endothelium-dependent contractions that are mediated by prostaglandin endoperoxides and suggest that they have properties other than simple inhibition of NO synthesis in porcine coronary arteries.

Cholinergic and α-adrenergic coronary constriction with increasing ischemia-reperfusion injury

Pages H886–H894: T. Ehring, M. Krajcar, D. Baumgart, S. Kompa, M. Hümmelgen, and G. Heusch. “Cholinergic and agr-adrenergic coronary constriction with increasing ischemia-reperfusion injury.” The title of this paper was incorrectly printed and should appear as the following. Cholinergic and agr-adrenergic coronary vasomotion with increasing ischemia-reperfusion injury.

Heterogeneity of vasomotor response to acetylcholine along the human coronary artery

In view of the segmental occurrence of coronary atherosclerosis, we postulated that acetylcholine may cause heterogeneous vasomotion, depending on the extent of vessel analyzed, criteria for change in vessel caliber and dose of drug administered. Previous studies have reported that acetylcholine causes constriction of atherosclerotic arteries. This dysfunction of endothelium-dependent dilation may be seen without angiographically detectable disease. We developed algorithms to quantitate the dimensions of a single coronary artery over virtually its entire length during a control state and during graded doses of intracoronary acetylcholine. On the basis of triplicate control angiograms, the limit of detection of a change from control diameter was 0.31 mm (> or = 2 SD). Analysis of multiple segments (each 5.6 +/- 1.1 [mean +/- SD] mm) along a single coronary artery revealed a heterogeneous response to acetylcholine in 27 of 31 patients at the 10(-4) mol/liter dose and in 29 of 31 patients when responses at 10(-6), 10(-5) and 10(-4) mol/liter doses were combined; in this latter analysis, constriction and dilation in the same vessel occurred in 45% of the patients. With acetylcholine, most of 349 segments demonstrated no change, but the greatest frequency of vasoconstriction (24.6%) and vasodilation (6.9%) was seen at the 10(-4) mol/liter dose. Inducible vasomotion was observed as far distally as 7.3 cm from the site of acetylcholine infusion. Response to intracoronary acetylcholine with mild coronary disease is heterogeneous; disparate dimensional responses may occur in different segments of the same vessel. Inclusion of all analyzable regions of a coronary artery and the use of a reproducibility limit for quantitative angiography are optimal for assessment of segmental coronary vasomotion.

Neurocardiology update: role of the nervous system in coronary vasomotion

Journal Article Neurocardiology update: role of the nervous system in coronary vasomotion Get access Douglas L Cordero, Douglas L Cordero aDepartment of Neurosciences, Graduate School of Biomedical Sciences, University of Medicine and Dentistry of New Jersey, 88 Ross St, East Orange, NJ 07019, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Norman A Cagin, Norman A Cagin bDepartment of Neurosciences, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, 88 Ross St, East Orange, NJ 07019, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Benjamin H Natelson Benjamin H Natelson * aDepartment of Neurosciences, Graduate School of Biomedical Sciences, University of Medicine and Dentistry of New Jersey, 88 Ross St, East Orange, NJ 07019, USA *Correspondence to Dr Natelson. Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 29, Issue 3, March 1995, Pages 319–328, https://doi.org/10.1016/S0008-6363(96)88587-7 Published: 01 March 1995 Article history Received: 11 March 1994 Accepted: 31 October 1994 Published: 01 March 1995

Neurocardiology update: role of the nervous system in coronary vasomotion

Neurocardiology update: role of the nervous system in coronary vasomotion

Reduction in Serum Cholesterol With Pravastatin Improves Endothelium-Dependent Coronary Vasomotion in Patients With Hypercholesterolemia

Reduction in Serum Cholesterol With Pravastatin Improves Endothelium-Dependent Coronary Vasomotion in Patients With Hypercholesterolemia

Management of vasospastic angina--role of nicorandil.

Clinical and experimental observations have confirmed that an episodic increase in the vasomotor tone of a major coronary artery may play a pathogenetic role not only in "variant angina" but also in other, more common anginal syndromes. In chronic stable angina, dynamic changes of vascular smooth muscle tone at the site of eccentric atheromatous plaques are responsible for "mixed angina." Abnormal coronary vasomotion contributes to myocardial ischemia in acute coronary syndromes as well. Studies have shown that a "primary" reduction of coronary blood flow, usually associated with plaque fissuring and thrombus formation, causes infarction and unstable angina. Abnormal vasoconstriction associated with the release of vasoactive substances by platelets and other constituents of the thrombus can contribute to coronary flow reduction in patients with unstable angina and myocardial infarction. Better understanding of the complex interactions among atherosclerotic coronary obstructions, the vascular smooth muscle, and the vascular endothelium has resulted in novel therapeutic approaches and has stimulated the search for more efficacious and safer coronary vasodilators. Recently interest has focused on vasodilator agents such as nicorandil that influence coronary arterial tone by acting through potassium channel activation. Nicorandil appears to be effective for treatment of vasospastic angina, as suggested by studies in Japan and Europe. In addition to its "antivasospastic" properties, nicorandil dilates coronary artery stenoses in patients with stable angina pectoris.(ABSTRACT TRUNCATED AT 250 WORDS)

Cholinergic and alpha-adrenergic coronary vasomotion [corrected] with increasing ischemia-reperfusion injury.

Ischemia-reperfusion-induced injury of the coronary vasculature could result in an attenuated vasodilator or increased vasoconstrictor tone that might impact on myocardial recovery and viability. In 30 open-chest dogs the left circumflex coronary artery was occluded for 15 or 60 min and then reperfused, and responses to intracoronary acetylcholine, the alpha 1-adrenergic agonist methoxamine, and the alpha 2-adrenergic agonist BHT-933 (n = 10 each) were measured. In the experiments with 60 min of occlusion, triphenyltetrazolium chloride (TTC) staining was used to distinguish reversibly (TTC+) and irreversibly (TTC-) injured myocardium. After 15 min of occlusion, the vasodilator response to acetylcholine was not altered but was significantly reduced in TTC+ subendocardium and midmyocardium after 60 min of occlusion and was further reduced in TTC- subendocardium, midmyocardium, and also in subepicardium. The vasoconstrictor responses to methoxamine and BHT-933 were not altered after 15 or 60 min of occlusion in both TTC+ and TTC- myocardium. Posterior wall thickening was not affected by acetylcholine, methoxamine, or BHT-933. Thus, in reversibly injured myocardium after 15 min of occlusion, cholinergic and alpha-adrenergic coronary vasomotor responses are unchanged. With increasing duration of ischemia, reversibly and even more so irreversibly injured reperfused myocardium are characterized by an impaired cholinergic coronary vasodilation but not an enhanced alpha-adrenergic coronary vaso-constriction.

Improvement of Coronary Vasomotion With Eicosapentaenoic Acid Does Not Inhibit Acetylcholine-Induced Coronary Vasospasm in Patients With Variant Angina.

Impaired function of the endothelium may be a mechanism of the coronary vasospasm induced by acetylcholine. We examined whether purified eicosapentaenoic acid (EPA), a major component of fish oil, improves the coronary vasomotion in response to acetylcholine, and the effect of purified EPA on acetylcholine (ACh)-induced coronary vasospasm in 22 patients with variant angina. ACh was infused into the coronary artery both before and after 4 months of EPA treatment (EPA 1.8 g/day, n = 12). In the control group (n = 10) that did not receive EPA, the response of the coronary diameter to ACh did not change over time. In the EPA-treated group, the cholinergic response in non-spastic sites changed from vasoconstriction to vasodilation, while ACh-induced coronary vasospasm persisted at the spastic sites. Therefore, EPA treatment improved the coronary vasomotor responsiveness to ACh, but did not inhibit ACh-induced coronary vasospasm.

Coronary vasomotion of the stunned myocardium.

The term “stunned” moycardium describes a dysfunction of the myocardium which may persist for hours, days or even weeks after restoration of coronary blood flow following thrombolysis, percutaneous transluminal coronary angioplasty (PTCA) or aorto-coronary bypass grafting (7, 9). The “stunned” myocardium is characterized — despite marked dyskinesis — by near normal levels of myocardial perfusion and normal or even enhanced oxygen consumption (2), probably due to higher oxygen requirements of the contractile elements. Thus, a mismatch between function and flow exists which has been recognized to be a characteristic finding of the “stunned” myocardium. However, coronary reperfusion may result in an attenuation of the endothelial response to coronary vasodilators such as acetylcholine, bradykinin, etc. (3). It is well established that prolonged myocardial ischemia is associated with irreversible myocardial damage and profound structural and functional derangements of the coronary microvasculature which may persist even if perfusion is restored (1). Local vasoactive substances such as the endothelium-dependent relaxing factor (EDRF) also play an important role in the regulation of myocardial perfusion. EDRF is a potent vasodilator which is released from the coronary endothelium but is reduced in patients with atherosclerotic plaques or hypercholesterolemia (= endothelial dysfunction). Since there are shear-stress dependent flow receptors, EDRF is released proportionally to coronary flow, i.e., the higher the flow the larger the artery and vice versa. However, flow regulation is dependent on several factors such as perfusion pressure, peripheral resistance, sympathetic activation, oxygen saturation, metabolic factors etc. EDRF is synthetized in the endothelial cells and is rapidly broken down during ischemia by superoxide radicals which inactivate EDRF and, thus, decrease flow-induced vasodilation (6). Neutrophil aggregation may further contribute to this process by the release of proteolytic enzymes which can convert oxygen to superoxide anions, i.e., oxygen free radicals. These radicals may injure the endothelium when generated in large amounts such as during ischemia (4) and may sensitize the smooth vasculature to contraction by alpha-adrenergic mechanisms (8).

Coronary vasoconstriction in response to acetylcholine after balloon angioplasty: possible role of endothelial dysfunction.

Abnormal endothelium-dependent vasomotion has frequently been observed early after coronary angioplasty. The aim of this study was to investigate endothelium-mediated coronary vasomotion caused by increasing intracoronary infusions of acetylcholine into epicardial coronary arteries 3-6 months after coronary angioplasty in patients without restenosis (50% luminal diameter reduction). Intracoronary acetylcholine was infused during follow-up coronary angiography followed by an intracoronary bolus of 250 g nitroglycerin in 18 patients who had undergone successful angioplasty of 21 isolated coronary artery lesions. Using an automated edge-detection program, coronary artery measurements were performed in the proximal reference segment, in the proximal part of the angioplasty site, at the site of previous maximal stenosis, in the distal part of the angioplasty site, and in the distal reference segment. In the segments of the coronary artery not manipulated by balloon catheter, acetylcholine did not produce significant luminal diameter changes (+2 +/- 23% in the proximal segment and -3 +/- 27% in the distal segment at 10(-4) mol/l). All the angioplasty vessel segments, excluding the proximal reference segments, showed an abnormal dose-related reactivity to the acetylcholine. Maximal vasoconstriction was observed at 10(-4) mol/l and was 4.9 +/- 11.1% in the proximal reference segment, 9.3 +/- 19.1% in the proximal angioplasty site (P = 0.0314), 20.3 +/- 24.1% at the site of previous maximal stenosis (P = 0.0005), 10.7 +/- 16.8% at the distal angioplasty site (P = 0.0098), and 9.3 +/- 14.1% in the distal reference segment (P = 0.0032). The maximal response of the angioplasty site to acetylcholine and to nitroglycerin did not correlate either with the time to follow-up or with the follow-up stenosis. Nitroglycerin-induced vasodilation was significant in all segments, but was lower in the lesion-related segments. Acetylcholine evoked the same effect on both the vessels that were manipulated and those that were not. Three to 6 months after coronary angioplasty, endothelium-dependent vasodilation was impaired not only at the site of previous maximal stenosis, but also in segments directly injured by balloon inflation. In contrast, endothelium-independent vasodilation by nitroglycerin is maintained in all segments. These observations suggest that the endothelium is still functionally impaired in the area of balloon dilation.

Coronary artery vasoconstriction after successful single angioplasty of the left anterior descending artery

Percutaneous transluminal coronary angioplasty is associated with spontaneous transient vasoconstriction. The mechanisms by which coronary vasoconstriction occurs distally to a successful dilated stenosis after coronary artery angioplasty are still unknown. The present study was planned to investigate the effect of successful coronary artery angioplasty on coronary vasomotion distal to a dilated stenosis and in the control vessel and the role of α-adrenergic receptors on coronary vasomotion after successful coronary artery angioplasty. We prospectively studied 32 consecutive patients scheduled for elective single coronary artery angioplasty of the left anterior descending coronary artery. Only aspirin, 325 mg, or nitroglycerin was allowed in the week before the study; no premedication with diazepam or other drugs was given. In group 1 (control patients, n = 20), quantitative coronary angiography was pertormed in the control state; 5 and 15 minutes after coronary artery angioplasty; and after intracoronary nitroglycerin infusion, 300 μg. In group 2 ( n = 12), intracoronary phentolamine, 2 mg, was infused regionally through the balloon catheter before the coronary artery angioplasty, and coronary angiography was pertormed at baseline, 15 minutes after balloon deflation, and after nitroglycerin infusion. In group 1, constriction of the coronary segment distal to a dilated stenosis (2.4 ± 0.8 to 2.1 ± 0.6 mm, −14.6% vs baseline; p < 0.05) and of the circumflex coronary artery segment (2.8 ± 0.7 to 2.5 ± 0.6 mm, −10.7% vs baseline, p < 0.05) occurred 15 minutes after coronary artery angioplasty. The degree of vasoconstriction was not correlated with the lesion severity before coronary artery angioplasty. In group 2, nonselective α-adrenergic blockade prevented distal vasoconstriction after coronary artery angioplasty (2.1 ± 0.4 vs 2.2 ± 0.4 mm; difference not significant), whereas significant vasoconstriction was observed in the control circumflex segments (2.7 ± 0.6 vs 2.4 ± 0.7 mm; p < 0.05). After successful coronary artery angioplasty of the left anterior descending coronary artery, constriction of the coronary segment distal to the site of balloon dilation and of the control segment in the circumflex coronary artery was observed. The degree of vasoconstriction of the segment distal to the stenosis was not correlated with lesion severity before coronary artery angioplasty. Pretreatment with regional α-adrenoceptor blockade abolished the coronary vasoconstriction. Therefore a generalized mechanism and α-adrenergic-mediated constriction may participate in the abnormal vasomotor changes after successful angioplasty. These findings may provide insight into the mechanisms of coronary vasoconstriction after coronary artery angioplasty.

Vasomotor response to ergonovine of epicardial and resistance coronary arteries in the nonspastic vascular bed in patients with vasospastic angina

The hypothesis that a coronary vasomotion disorder may exist in the entire coronary artery tree in patients with vasospastic angina was investigated by examining the coronary responses to atrial pacing (130 beats/min) before and after the administration of ergonovine (16 μg) into nonspastic coronary arteries. Seven patients with angiographically normal coronary arteries and focal spasm in the right coronary artery and 7 control patients with atypical chest pain and angiographically normal coronary arteries without spasm were studied. Great cardiac vein flow (GCVF) and left anterior descending coronary artery diameters (CDs) were measured by the thermodilution method and quantitative arteriography, respectively. Although the CDs before ergonovine were similar in the 2 groups, the pacing-induced increase in GCVF before ergonovine administration was smaller in patients with vasospastic angina than in control patients (22 ± 4% vs 49 ± 11%, respectively; p <0.05). After ergonovine administration, pacing both increased GCVF and decreased anterior regional coronary resistance (ACR) to a lesser extent in patients with vasospastic angina than in control patients (GCVF, 16 ± 4% vs 47 ± 8%, respectively [p <0.01]; ACR, −12 ± 3% vs −29 ± 3%, respectively [p <0.01]). The decreases in CDs in patients with vasospastic angina observed after ergonovine administration were greater than those in control patients (−18 ± 2% vs −9 ± 2%, respectively; p <0.05). Thus, not only epicardial, but also resistance coronary arteries are affected by the coronary vasomotion disorder in the nonspastic vascular bed in patients with vasospastic angina.

Pathophysiology of Angina Pectoris--Coronary Anatomy and Vasomotion

Journal Article Pathophysiology of Angina Pectoris—Coronary Anatomy and Vasomotion Get access European Heart Journal, Volume 15, Issue suppl_3, September 1994, Pages 320–322, https://doi.org/10.1093/eurheartj/15.suppl_3.320 Published: 12 September 1994

Coronary artery constriction caused by the cold pressor test in human hypertension.

Hypertensive patients with angiographically normal coronary arteries may have myocardial ischemia when metabolic demand increases. Abnormal epicardial coronary artery vasomotion in response to sympathetic stimulation may contribute to ischemia in such patients. We studied the vasomotor response of smooth coronary arteries to a cold pressor test in 10 hypertensive patients without other risk factors and in 9 control subjects. Vessel dimensions were measured by quantitative angiography, and blood flow was calculated using an intracoronary Doppler catheter in the left anterior descending coronary artery. In response to cold pressor stimulation, arteries of control subjects dilated 13.0 +/- 5.9% (P < .001), and they constricted 8.2 +/- 8.5% in hypertensive patients (P < .001). Rate-pressure product increased from 9466 +/- 1677 to 12,547 +/- 2367 beats per minute (bpm).mm Hg in control subjects (P < .001) and from 13,720 +/- 1823 to 17,353 +/- 2037 bpm.mm Hg in hypertensive patients (P < .001). Coronary blood flow velocity and blood flow increased 51 +/- 26% (P < .05) and 87 +/- 27% (P < .001), respectively, in control subjects and 68 +/- 52% (P < .05) and 36 +/- 33% (P < .01) in hypertensive patients. At peak cold pressor test, despite a significant higher rate-pressure product in hypertensive patients, blood flow was similar in both groups, suggesting an uncoupling between myocardial metabolic demand and supply. Thus, hypertension impairs the vasodilator response of angiographically normal coronary arteries to a cold pressor test. This abnormal response may be due to enhanced catecholamine reactivity and/or impairment of endothelial flow-mediated vasodilator response.

Role of vascular endothelium in exercise-induced dilation of large epicardial coronary arteries in conscious dogs.

The role of vascular endothelium in the control of epicardial coronary artery vasomotion during treadmill exercise remains unclear. Therefore, we examined the consequences of in vivo balloon endothelial denudation on external coronary diameter of the left circumflex artery during exercise in conscious dogs. Seven dogs instrumented for the measurement of arterial blood pressure, external coronary artery diameter, and coronary blood flow were studied during exercise before and up to 21 days after balloon endothelial denudation of the proximal left circumflex artery. Endothelial denudation was confirmed by abolition of the epicardial coronary artery dilation induced by acetylcholine (0.3 microgram/kg IV) and reactive hyperemia. Epicardial coronary vasodilation was observed in the control state during treadmill exercise (+5.2 +/- 1.0%). In contrast, a marked vasoconstriction was observed 3 (-4.6 +/- 0.6%) and up to 6 days after endothelial denudation. Complete epicardial coronary artery dilation in response to acetylcholine and exercise was restored 9 days after endothelial denudation. In addition, epicardial coronary artery vasomotor responses to acetylcholine and treadmill exercise were closely correlated (r = .82, P < .001). Reactive dilation was not completely restored 21 days after endothelial denudation, but reactive hyperemia and exercise vasomotor responses during the 21 days follow-up were correlated (r = .70, P < .001). Vasodilation induced by nitroglycerin (1 microgram/kg IV) was reduced by 25% (P < .01) 3 days after endothelial denudation and returned to its corresponding control level 3 days later. Prazosin (50 micrograms/kg IV) significantly attenuated the exercise-induced coronary artery constriction after endothelial denudation (+1.5 +/- 1.4% versus -4.6 +/- 1.0%). These data demonstrate that endothelium is essential for the mediation of epicardial coronary dilation during exercise and may protect these vessels against the vasoconstrictor effect of endogenous catecholamines.

Reduction in serum cholesterol with pravastatin improves endothelium-dependent coronary vasomotion in patients with hypercholesterolemia.

This study aimed to determine if cholesterol-lowering therapy improves endothelium-dependent coronary vasomotion in patients with hypercholesterolemia. Nine patients with hypercholesterolemia were studied before and after cholesterol-lowering therapy with pravastatin (an inhibitor of HMG-CoA reductase) for 6 +/- 3 months, which lowered serum cholesterol from 272 +/- 8 to 187 +/- 16 mg/dL (P < .01). Control patients with serum cholesterol of 218 +/- 23 mg/dL also were studied twice in a similar interval (8 +/- 2 months) with no cholesterol-lowering drugs. Acetylcholine (the endothelium-dependent vasodilator) and papaverine and nitrate (endothelium-independent vasodilators) were infused into the study coronary artery. Changes in the diameter of the epicardial coronary artery and coronary blood flow were assessed by quantitative coronary arteriography and an intracoronary Doppler catheter. In patients with hypercholesterolemia, acetylcholine-induced vasoconstriction of the epicardial artery was less (P < .05) and the acetylcholine-induced increases in coronary blood flow were greater (P < .001) after than before pravastatin. In control patients, responses of the epicardial coronary artery and coronary blood flow to acetylcholine did not change over the follow-up period. The vasomotor responses to papaverine or nitrate were similar between the two groups, and no interval changes in their responses were noted in either group. These results suggest that cholesterol-lowering therapy with pravastatin may improve endothelium-dependent coronary vasomotion, which may possibly contribute to the improvement of myocardial perfusion as well as the regression of coronary atherosclerosis.

The role of ATP-sensitive potassium channels in regulating coronary microcirculation.

The ATP-sensitive potassium channel (K+ATP channel) is known to exist in blood vessels and to regulate vascular tone. We examined the role of this channel in coronary arteriolar vasomotion during coronary autoregulation, ischemia, reactive hyperemia and endothelium-dependent response by acetylcholine in vivo. Experiments were performed with anesthetized open-chest dogs. Coronary arterioles were directly observed in situ by means of a floating objective system or a stroboscopic epi-illumination system synchronized with cardiac motion. Small arterioles less than 100 microns in internal diameter dilated in response to reduction in perfusion pressure (perfusion pressure: 60, 40, 25 mm Hg). Glibenclamide, a selective blocker of the K+ATP channel, reversed the dilation. Reactive hyperemia produced by 20-second occlusion of the left anterior descending coronary artery resulted in arteriolar dilation, the magnitude of which was greater in smaller arterioles than in larger ones. Glibenclamide significantly inhibited the dilation in both large and small arterioles. Acetylcholine (ACh) produced dilation in arterioles of all sizes. NG-monomethyl L-arginine, a competitive inhibitor of nitric oxide synthesis, abolished the dilation of large arterioles, but failed to abolish the dilation in small arterioles. Glibenclamide, however, did not have any additional inhibitory effect on ACh-induced arteriolar dilation. Thus, we conclude that the K+ATP channel plays an important role in coronary microvascular vasomotion during autoregulation, ischemia and reactive hyperemia, but not during endothelium-dependent vasodilation induced by ACh in vivo.