Mean Coronary Vascular Resistance Research Articles

Effect of beta‐adrenergic blockade on coronary blood flow during isometric exercise in older adults (875.7)

The rise in heart rate (HR) and cardiac contractility during exercise is due to activation of myocardial β‐adrenergic receptors. In animals, β‐adrenergic receptors in the coronary vasculature also mediate a parallel increase in coronary blood flow. However, the role of β‐ adrenergic receptors in the human coronary circulation is unknown. We hypothesized that β‐adrenergic blockade with propranolol would attenuate reflex tachycardia and coronary hyperemia in response to isometric handgrip in healthy older adults. Six men (66 ± 2 yrs) performed isometric handgrip exercise at 40% of maximal voluntary contraction for 2 minutes after receiving intravenous propranolol or no treatment. HR and blood pressure were monitored continuously and rate‐pressure product (RPP) was calculated as an index of myocardial oxygen demand. Coronary blood flow velocity (CBV) was measured by transthoracic Doppler echocardiography and coronary vascular resistance (CVR) was calculated. The coronary supply to demand ratio was calculated as CVR/RPP. Propranolol decreased the HR (8 ± 3 vs. 4 ± 1) and RPP (2580 ± 612 vs. 1520 ± 163) responses to exercise but augmented the CVR/RPP response (‐0.24 ± .09 vs. ‐0.49 ± 0.15). Mean arterial pressure, CVR and CBV were unaltered. β‐adrenergic blockade not only decreased myocardial oxygen demand in response to exercise, it also improved oxygen supply.Grant Funding Source: Supported by NIH P01 HL096570 and UL1 TR000127

Cardioprotective effect of orally administered angiotensin-converting enzyme inhibitor against ischemia. Reperfusion injury in the isolated rat heart.

Angiotensin-converting enzyme inhibitors are reported to be cardioprotective against ischemia/reperfusion injury. Few studies have been made, however, on the cardioprotectiveness of orally administered angiotensin-conrerting enzyne inhibitors. Wistar rats were pretreated with oral delapril--30 mg/kg/day in the low-dose group and 90 mg/kg/day in the high-dose group--for one week. Cardiac function recovery was assessed after ischemia/reperfusion in the isolated working heart model. Rat hearts in the high-dose group were also reperfused with a solution containing nitro-L-arginine methyl ester, a nitric-oxide synthase inhibitor. Oral pretreatment of delapril did not affect baseline cardiac function. The percentage of cardiac output recovery for controls was 22 +/- 4.5%, for the low-dose group 44 +/- 6.5% (P < 0.05 versus controls), and for the high-dose group 76 +/- 5.3% (P < 0.001 versus controls and low-dose). Although coronary vascular resistance at the end of reperfusion showed no difference, mean coronary vascular resistance early after reperfusion was significantly lower (P < 0.0001) in both delapril groups than in control. In the high-dose group, reperfusion with L-NAME significantly increased coronary vascular resistance after ischemia/reperfusion and attenuated the cardioprotectiveness of delapril (P < 0.05 versus without nitro-L-arginine methyl ester). We thus found that oral administration of delapril was cardioprotective dose-dependently against ischemia/reperfusion injury. Nitric oxide appeared to be involved in the mechanism behind this cardioprotective effect.

Intraoperative Assessement of Coronary Flow and Coronary Vascular Resistance During Coronary Bypass Surgery

The measurement of coronary graft flow rates is a well-established method of assessing graft function intraoperatively. In order further to understand the dynamics of graft function, the resistance to the flow was considered a desirable measurement intraoperatively. The coronary vascular resistance (CVR) was estimated by applying the Poiseuille-Hagen equation. The CVR was estimated at zero cardiac work (during cardioplegic arrest) using fixed perfusion flow rates and estimating the pressures produced. After going off cardiopulmonary bypass (CPB), the bypass graft flow (F) was estimated by a standard utrasound Doppler technique. The perfusion pressure over the perfused coronary graft was then determined and the CVR in the working heart ascertained. The CVR was studied in 178 vein grafts in 59 patients undergoing coronary bypass surgery. The mean CVR in the cardioplegic heart (c-CVR) varied from 0.81 to 2.3 mmHg/ml/min for various coronary artery diameters and was significantly higher in small diameter arteries compared with larger arteries (p < 0.0002). Consequently significant high flows were found in the large vessels compared with the smaller ones (p

Coronary vascular and myocardial effects of substance P in hypercholesterolemic rabbits

Age-matched male New Zealand white rabbits (n = 16) were allocated to two groups: group 1 (n = 8) received a standard rabbit diet; group 2 (n = 8) received a 2% cholesterol-enriched diet. After 8 weeks of prescribed diet, hearts were excised and placed on a constant perfusion pressure Langendorff-type apparatus. Coronary flow, left ventricular pressure, and isovolumic dP dt were continuously measured. Baseline recordings were made and then a single 5 nmol bolus dose of substance P was delivered into the coronary perfusate. Mean serum cholesterol levels in group 1 were 53 ± 17 (SEM) mg·dl −1, in group 2 1438 ± 143 mg·dl −1. In group 1, the injection of substance P caused mean coronary flow to increase 39 ± 6%, mean coronary vascular resistance to decrease 28 ± 3%, and mean dP dt to increase 11 ± 4%. In group 2, coronary flow increased 57 ± 13%, coronary vascular resistance decreased 33 ± 5%, and dP dt increased 17 ± 4%. Within groups, values changed significantly from baseline but these changes were not significantly different between groups. The duration of coronary flow response was 113 ± 20 s in group 1 and 63 ± 8 s in group 2. Substance P is a potent dilator of coronary resistance vessels and has positive inotropic effects in the rabbit. High levels of cholesterol exposure do not alter the magnitude of substance P-induced vasodilation, but the duration of the response is shortened.

Transmural heterogeneity of postjunctional alpha 2 adrenergic coronary vasoconstriction in hypoperfused cat left ventricle.

The aim was to analyse the influence of coronary postjunctional alpha 1 and alpha 2 adrenergic vasoconstriction in hypoperfused myocardium with special emphasis on transmural distribution of blood flow. The left coronary artery was hypoperfused by means of a clamped shunt line. Sequential selective postjunctional alpha 1 (doxazosin) and alpha 2 (SK&F 104078) adrenergic antagonism was established following beta adrenergic antagonism with propranolol. Regional myocardial blood flow was measured with radiolabelled microspheres during equal coronary perfusion pressures. Experimental subjects were nine pentobarbitone anaesthetised open chest cats. Left coronary hypoperfusion decreased endocardial blood flow, whereas epicardial flow was unaltered. In this situation alpha 1 adrenergic antagonism did not affect myocardial blood flow. Subsequent alpha 2 antagonism impaired endocardial blood flow, whereas epicardial blood flow was augmented. Mean coronary vascular resistance declined following combined alpha 1 and alpha 2 adrenergic antagonism. Coronary alpha adrenergic vasoconstriction is localised mainly epicardially in hypoperfused myocardium and counteracts endocardial hypoperfusion distal to a fixed coronary stenosis. Furthermore, this vasoconstriction is of the postjunctional alpha 2 adrenergic subtype.

Myocardial ischaemia and ventricular arrhythmias precipitated by physiological concentrations of adrenaline in patients with coronary heart disease.

The clinical and haemodynamic effects of adrenaline infusion (30 ng kg-1 min-1) producing plasma adrenaline concentrations in the range seen during acute myocardial infarction and of placebo were investigated in a crossover design in 14 patients with stable coronary heart disease. Adrenaline infusion resulted in electrocardiographic evidence of myocardial ischaemia (greater than or equal to 1 mm (0.1 mV) horizontal or downsloping ST segment depression) in 10 patients and angina in four, although the mean (SEM) increase in heart rate was modest (14 (2) beats/min) and mean coronary vascular resistance fell from 1.56 (0.21) to 1.16 (0.14) mm Hg min ml-1 (p less than 0.005). New or increasingly frequent or complex ventricular arrhythmias occurred in five patients. Placebo infusion had no effect on the variables measured. Supine bicycle exercise during infusion of the saline placebo was associated with a similar degree of ST segment depression (0.9 (0.2) mm) as adrenaline infusion at rest (0.9 (0.1) mm) but exercise performed during adrenaline infusion (10 patients) resulted in more pronounced ST segment depression (1.9 (0.3) mm) (p less than 0.005) than either intervention alone. Angina occurred in three of 11 patients during control exercise and in six of 10 during the combination of adrenaline infusion and exercise. Such potentially adverse consequences of low dose adrenaline infusion in patients with stable coronary heart disease are consistent with the suggestion that adrenal activation is detrimental during acute myocardial infarction, being both arrhythmogenic and proischaemic.

Effect of arginine vasopressin on coronary and systemic hemodynamics in man

Arginine vasopressin is a potent constrictor of isolated arterial segments in vitro. However, it is disputed whether, in vivo, arginine vasopressin acts as either a systemic or coronary vasoconstrictor. The purpose of this study was to determine the effect of arginine vasopressin on coronary and systemic vascular tone in man. Six patients undergoing routine diagnostic cardiac catheterization were studied. At angiography, all patients were found to have severe coronary artery disease. Cardiac and systemic pressures and coronary blood flow as well as serum arginine vasopressin and osmolality levels were measured before and after administration of hypertonic contrast dye and then following intravenous injection of an analog inhibitor of arginine vasopressin. At baseline, serum arginine vasopressin levels were within the normal range in all patients, but, following infusion of contrast dye, rose above physiological levels in 5 patients. In these latter patients, there were no significant changes in coronary and systemic hemodynamics between baseline (condition 1), following administration of contrast dye (condition 2) and 10 minutes after injection of arginine vasopressin inhibitor (condition 3). Mean coronary sinus blood flow (ml/min) and mean coronary vascular resistance (dyne·sec·cm −5) were 184±49 and 41,235±8275 during condition 1, 204±62 and 39,442±8781 during condition 2, and 192±75 and 44,930±11455 during condition 3. Mean arterial pressure (mm Hg) and mean systemic vascular resistance (dyne·sec·cm −5) during conditions 1, 2 and 3 were 105 ± 12 and 1454 ± 174, 114 ± 21 and 1432 ± 210, and 114 ± 15 and 1436 ± 147, respectively. These data suggest that arginine vasopressin has no effect on coronary or systemic vascular tone in patients with coronary artery disease.

The effect of coronary artery occlusion on the cardiovascular response to an aversive stress.

The cardiovascular response to a controlled aversive stress was investigated both before and during acute myocardial ischemia. Classical aversive conditioning (a 30-s tone reinforced with a 1-s shock) served as the model of stress while anterior wall myocardial ischemia was induced by the occlusion (hydraulic occluder) of the left anterior descending coronary artery. The conditional response consisted of significant increases (P less than 0.01) in mean arterial pressure (AP, 13.8 +/- 1.9 mm Hg, 14.3%), left ventricular (LV) dP/dtmax (1300 +/- 324 mm Hg/s, 34.7%) and heart rate (HR, 44 +/- 4 beats/min, 46.8%). Mean coronary vascular resistance significantly (P less than 0.01) increased first (CVR, 0.52 +/- 0.18 mm Hg/ml/min, 17.2%), then decreased (0.77 +/- 0.14 mm Hg/ml/min, 25.5%). In contrast, during acute myocardial ischemia both the HR and d(LVP)/dtmax conditional response were significantly reduced (P less than 0.01) by 58 and 54%, respectively (HR, 20.7 +/- 3.8 beats/min, d(LVP)/dt, 756 +/- 226 mm Hg/s). In addition, the initial CVR increase was virtually eliminated (0.13 +/- 0.10 mm Hg/ml/min, 74.0% reduction) while the CVR decrease was significantly reduced (P less than 0.01) by 48% (0.40 +/- 0.15 mm Hg/ml/min) during the coronary occlusion. The mean AP response, however, was not affected by myocardial ischemia. The pre-conditional stimulus cardiovascular variables were similarly unaffected by the coronary artery occlusion. Thus, coronary artery occlusion attenuated both the coronary and cardiac response elicited by an aversive stress. The mechanism mediating this inhibition of the conditional response remains to be determined but may involve the activation of vagal depressor reflexes during the acute ischemia.

Myocardial blood flow in left ventricular hypertrophy developing in young and adult dogs.

This study was performed to test the hypothesis that growth of coronary vasculature would be facilitated if myocardial hypertrophy occurred during the period of normal body growth rather than in mature adult animals. Left ventricular hypertrophy was produced by banding the ascending aorta in eight young dogs 7 wk of age and in nine adult dogs. Adult dogs were studied 2 mo after aortic banding, whereas young dogs were allowed to grow to adulthood before study. Left ventricular weight-to-body weight ratios were increased to 6.88 +/- 0.36 g/kg in the young dogs and 6.64 +/- 0.47 in adult dogs; both were significantly greater than seven normal control animals (4.32 +/- 0.05; each P less than 0.01). Myocardial blood flow per gram measured with microspheres during quiet resting conditions was significantly higher in young dogs with left ventricular hypertrophy than in normal dogs. Myocardial blood flow rates during maximum coronary vasodilation with adenosine (4 mumol X kg-1 X min-1 iv) were similar in all three groups. However, since mean coronary perfusion pressure was higher in the dogs with aortic banding, minimum coronary vascular resistance per gram of myocardium was significantly higher in both young (21.1 +/- 3.1 mmHg X ml-1 X min X g) and adult dogs with left ventricular hypertrophy (21.8 +/- 2.2) than in the normal dogs (16.8 +/- 3.1; each P less than 0.01). Mean coronary vascular resistance for the total left ventricle was similar in all three groups of animals, suggesting that growth of coronary vasculature did not occur as the myocardium underwent hypertrophy.(ABSTRACT TRUNCATED AT 250 WORDS)

THE EFFECT OF THE CORONARY VASCULAR WALL ON THE CHANGES IN THE CORONARY VASCULAR RESISTANCE DURING A SUDDEN REDUCTION AND RECOVERY OF THE AORTIC BLOOD PRESSURE

To demonstrate the effect of elastic and myogenic properties of the vessel wall on the mean coronary vascular resistance during ventricular diastole (m.d.c.r.), this resistance was assessed in twenty dogs anaesthetized with sodium pentobarbitone during a 10 s period of arterial haemorrhage and 20 s of recovery from this haemorrhage. In a first stage of the study ten dogs were investigated following sectioning of the vagal nerves in the neck, beta-blockade, and ligation of the carotid arteries. During haemorrhage and reduction in aortic blood pressure (A.B.P.) in these dogs, there was an initial rise (at 2 s after the start of the haemorrhage) in m.d.c.r. which quickly decreased to a value similar to that obtained during the control period. After the abrupt cessation of haemorrhage, and a rise in A.B.P., there was an initial decrease in m.d.c.r. which eventually increased to the control levels. In the second stage of study identical patterns of changes were obtained in a group of five dogs in which the cervical vagi were not sectioned and beta-blocking agents not given. In another group of five dogs, during infusion of dipyridamole to force maximal coronary vasodilation, the increase in m.d.c.r. was maintained throughout the period of haemorrhage and reduction in A.B.P., and m.d.c.r. did not decrease below the control values following the abrupt cessation of haemorrhage and a rise in A.B.P. The findings in the dogs without dipyridamole infusion suggested that the pattern of changes in m.d.c.r. was due to changes in the perfusion pressure and their effect on the elasticity and myogenic properties of the coronary vascular wall. This suggestion was supported in the second stage of the study, when the reductions in m.d.c.r. were abolished by forcing coronary vasodilation using the infusion of dipyridamole.

Regulation of the right coronary circulation during a controlled behavioral stress in the conscious dog

Right coronary blood flow (CBF) was measured in 11 mongrel dogs during classical aversive conditioning (a 30 s tone followed by a 1 s 2–6 mA electrical shock). The cardiovascular response consisted of significant ( P < 0.01) increases in: (a) mean arterial pressure (12.9%), (b) systolic right ventricular pressure (RVP, 31.8%), (c) d(RVP)/ dt (49.9%) and heart rate (56.2%). The coronary vascular response to behavioral stress consisted of an immediate and significant increase in mean CBF (56.9%) coupled with a significant decrease in mean coronary vascular resistance (CVR, −28.5%). The mean CVR decrease was reduced by cardioselective β-blockade (CBB) or cardiac pacing and eliminated by right stellectomy (RSGx). The combination of CBB with cardiac pacing resulted in a significant increase in mean CVR. α-adrenergic blockade with either phentolamine or prazosin, RSGx, and cardiac pacing significantly reduced the control mean CVR values. Thus, these data suggest that the right coronary response to stress is primarily mediated by the release of metabolic factors secondarily to an increased inotropic or chronotropic state. However, when these metabolic effects were controlled, mean coronary resistance no longer decreased but, rather, increased in response to the aversive stress. This increase could be eliminated by the addition of an α-adrenergic antagonist. These data further suggest that the coronary response to behavioral stress activates an α-adrenergic vasoconstriction.

Effect of activation of the H1 receptor on coronary hemodynamics in man.

We evaluated the effects of selective activation of H1 receptors on coronary hemodynamics in 16 patients divided into two groups: group A, 11 patients with atypical angina or valvular heart disease and normal coronary arteries, and group B, five patients with spontaneous angina, four of whom had significant (greater than 70% stenosis) coronary artery disease and one with normal coronaries. Selective H1 receptor stimulation was achieved by infusing 0.5 microgram/kg/min of histamine intravenously for 5 min after pretreatment with cimetidine (25 mg/kg). Heart rate was maintained constant (100 beats/min) by coronary sinus pacing and coronary blood flow (CBF) was measured by thermodilution. In group A, during histamine infusion mean aortic pressure fell from 99 +/- 5 to 77 +/- 4 mm Hg (mean +/- SEM, p less than .001), coronary vascular resistance (CVR) decreased from 1.07 +/- 0.17 to 0.82 +/- 0.14 mm Hg/ml/min (p less than .02), and CBF and myocardial oxygen consumption remained unchanged. None of the patients in this subgroup developed angina during histamine infusion. In group B, while no significant average changes in mean arterial pressure, CVR, or CBF were observed, two of the five patients (40%) developed angina during histamine infusion, accompanied by ST-T elevation, a decrease in CBF, and an increase in CVR. In one of these two patients circumflex coronary arterial spasm was angiographically demonstrated during histamine-induced angina. Our results suggest that stimulation of the H1 receptor induces a reduction of CVR, probably resulting from vasodilation of small coronary resistance vessels.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary and Systemic Hemodynamic Effects of Tetramethylpyrazine in the Dog

The hemodynamic effects of tetramethylpyrazine were examined in 27 anesthetized open chest dogs with electromagnetic flowmeter probes on the left circumflex coronary artery and ascending aorta. Tetramethylpyrazine, 2-15 mg/kg i.v., caused prominent systemic and coronary vasodilation, with a maximum reduction of mean aortic pressure from 92 +/- 5 mm Hg during control conditions to 62 +/- 7 mm Hg (p less than 0.01), a peak increase in cardiac output from 3.0 +/- 0.4 to 4.1 +/- 0.7 L/min (p less than 0.05), and a peak reduction of systemic vascular resistance from 2,450 +/- 400 to 1,210 +/- 329 dyne X s X cm-5 (p less than 0.01). Simultaneously, heart rate increased from 143 +/- 9 to 174 +/- 8 beats/min (p less than 0.01), and maximum left ventricular dP/dt increased from 2,410 +/- 120 to 4,020 +/- 60 mm Hg/s (p less than 0.01). Dose-related increases of coronary blood flow occurred from 37.3 +/- 3.7 to a maximum of 74.1 +/- 6.6 ml/min (p less than 0.01), while mean coronary vascular resistance decreased from 1,770 +/- 240 to 700 +/- 260 dyne X s X cm-3 (p less than 0.01). Myocardial oxygen consumption increased in proportion to the increase in coronary blood flow. Following beta-adrenergic blockade with propranolol (1 mg/kg, i.v.), ganglionic blockade with hexamethonium, or catecholamine depletion with reserpine (1.0 mg/kg, i.p.), the systemic and coronary vasodilator effects of tetramethylpyrazine persisted, but the increases in heart rate, maximum left ventricular dP/dt, and myocardial oxygen consumption were markedly attenuated.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary blood flow in experimental canine left ventricular hypertrophy.

To determine whether left ventricular hypertrophy [LVH] altered total and regional coronary blood flow, we inflated a balloon around the ascending aorta of nine dogs; six acute and six sham-operated dogs were controls. After 6 weeks, all dogs were studied with an open chest under anesthesia; the balloons were deflated. There was moderate LVH as shown by increased left ventricular weight and fiber diameter. At rest there were no major differences of coronary flow or resistance per gram of muscle. With maximal coronary vasodilation due to adenosine or carbochrome, mean coronary vascular resistance was 84% higher in LVH than in normal hearts; with isoproterenol, resistance was 54% higher in LVH. These changes were similar in right and left ventricles. Minimal coronary resistance at end diastole also was higher in LVH--64% and 94% for the two sets of vasodilators, respectively. There were no significant differences in capillary or large vessel proportional volumes in LVH and control dogs, but arterial capacity could not be estimated. The raised minimal coronary resistance suggests the possibility that, with stress, coronary flow, especially to subendocardial muscle, might be inappropriate and perhaps cause ischemic damage. However, the changes noted might have been due to coronary arterial responses to raised coronary pressures rather than to hypertrophy itself.

Effects of morphine on coronary and left ventricular dynamics in conscious dogs.

We studied the effects of i.v. 2 mg/kg morphine sulfate (MS) on coronary blood flow and resistance, left ventricular (LV) diameter and pressure (P), rate of change of pressure (dP/dt), and dP/dt/P in conscious dogs. An initial transient reduction in coronary vascular resistance, associated with increases in heart rate, dP/dt, dP/dt/P, and reductions in LV end-diastolic and end-systolic size were observed. This was followed by a prolonged increase in mean coronary vascular resistance, lasting from 5 to 30 min, while heart rate, arterial pressure, and LV end-diastolic diameter returned to control levels and dP/dt/P remained slightly but significantly above control. At 10 min, late diastolic coronary flow had fallen from 44 plus or minus 3 ml/min to a minimum level of 25 plus or minus 3 ml/min, while late diastolic coronary resistance had risen from 1.68 plus or minus 0.10 to 3.04 plus or minus 0.28 mm Hg/ml/min. Morphine also induced substantial coronary vasoconstriction when heart rate was held constant. Neither the MS-induced coronary vasoconstriction nor the positive inotropic response was abolished by bilateral adrenalectomy. The positive inotropic response of MS was reversed after beta blockade, but not the coronary vasoconstriction. Alpha receptor blockade abolished the late coronary vasoconstriction effects of morphine, and only dilatation occurred. In anesthetized dogs MS failed to produce late coronary vasoconstriction. Coronary after a respiratory-depressant dose of morphine, 10 mg/kg i.v. Smaller doses of MS, 0.25 mg/kg every 15 min, produced significant coronary vasoconstriction after a total dose of 0.75 mg/kg in the conscious dogs. The effects of morphine may differ in the normal dog and man and may vary depending upon the presence or absence of coronary artery disease. However, in the normal conscious dog, MS elicits a mild beta adrenergic increase in contractility and an important coronary vasoconstrictor effect, which is mediated through alpha adrenergic receptors.

Effects of norepinephrine on coronary circulation and left ventricular dynamics in the conscious dog.

The effects of norepinephrine (0.1 and 1.0 µg/kg, iv) on coronary blood flow and resistance, left ventricular pressure and diameter, dP/dt, (dP/dt)/P, and the velocity (V ISO ) of myocardial fiber shortening were studied in conscious dogs. When the heart rate was held constant, norepinephrine caused an initial reduction in coronary vascular resistance which was associated with increases in mean arterial blood pressure, systolic left ventricular pressure, end-diastolic diameter, dP/dt, (dP/dt)/P, and V ISO . After this brief coronary vasodilator response, a sustained increase occurred in mean coronary vascular resistance (+0.55 ± 0.07 mm Hg/ml min -1 ), and increases persisted in mean arterial blood pressure (+67 ± 7 mm Hg), left ventricular systolic pressure (+74 ± 6 mm Hg), left ventricular end-diastolic pressure (+4 ± 1 mm Hg), left ventricular internal diameter (+1.3 ± 0.3 mm), peak dP/dt (+1660 mm Hg/sec), (dP/dt)/P (+15 ± 2 sec -1 ), and V ISO (+11 ± 2 mm/sec); coronary sinus Po 2 decreased. Beta-receptor blockade prevented the inotropic effects of norepinephrine, attenuated the early coronary vasodilator effects, and increased the late vasoconstrictor effects. Alpha-receptor blockade abolished the late coronary vasoconstrictor effects of norepinephrine; only dilatation occurred. In contrast to the effects of norepinephrine in conscious dogs without autonomic blockade , norepinephrine (1.0 µg/kg, iv) failed to produce late coronary vasoconstriction in anesthetized, open-chest dogs; only dilatation occurred. Thus, in the normal, conscious dog, norepinephrine exerts an important coronary vasoconstrictor effect which is sufficiently intense to counteract completely the simultaneous tendency toward metabolic vasodilatation.