alpha-Adrenergic control of oxygen delivery to myocardium during exercise in conscious dogs

Heyndrickx, Guy R.; Muylaert, P.; Pannier, Jean

doi:10.1152/ajpheart.1982.242.5.h805

Cited by 44 publications

(51 citation statements)

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“…␣-Adrenoceptor-mediated coronary vasoconstriction can compete with local metabolic vasodilation, as has been shown in a number of studies in dogs, limiting the coronary vascular response during sympathetic activation, e.g., exercise (4,7,9,19), norepinephrine infusion, or carotid sinus reflex (18). The role of ␣-adrenoceptor-mediated coronary vasoconstriction has also been investigated during maximal vasodilation to overcome the confounding influence of autoregulation.…”

Section: Discussionmentioning

confidence: 99%

Systemic nitric oxide synthase inhibition improves coronary flow reserve to adenosine in patients with significant stenoses

Kaufmann

Rimoldi

Gnecchi‐Ruscone

et al. 2007

American Journal of Physiology-Heart and Circulatory Physiology

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Kaufmann PA, Rimoldi OE, Gnecchi-Ruscone T, Luscher TF, Camici PG. Systemic nitric oxide synthase inhibition improves coronary flow reserve to adenosine in patients with significant stenoses. Am J Physiol Heart Circ Physiol 293: H2178-H2182, 2007. First published July 27, 2007; doi:10.1152/ajpheart.01292.2006.-We studied the impact of systemic infusion of the nitric oxide synthase (NOS) inhibitor N G -monomethyl-L-arginine (L-NMMA) on coronary flow reserve (CFR) in patients with coronary artery disease (CAD). We have previously demonstrated that CFR to adenosine was significantly increased after systemic infusion of L-NMMA in normal volunteers but not in recently transplanted denervated hearts. At baseline, myocardial blood flow (MBF; ml ⅐ min Ϫ1 ⅐ g Ϫ1 ) was measured at rest and during intravenous administration of adenosine (140 g ⅐ kg Ϫ1 ⅐ min Ϫ1 ) in 10 controls (47 Ϯ 5 yr) and 10 CAD patients (58 Ϯ 8 yr; P Ͻ 0.01 vs. controls) using positron emission tomography and 15 O-labeled water. Both MBF measurements were repeated during intravenous infusion of 10 mg/kg L-NMMA. CFR was calculated as the ratio of MBF during adenosine to MBF at rest. CFR was significantly higher in healthy volunteers than in CAD patients and increased significantly after L-NMMA in controls (4.00 Ϯ 1.10 to 6.15 Ϯ 1.35; P Ͻ 0.0001) and in patients, both in territories subtended by stenotic coronary arteries (Ͼ70% luminal diameter; 2.06 Ϯ 1.13 to 3.21 Ϯ 1.07; P Ͻ 0.01) and in remote segments (3.20 Ϯ 1.23 to 3.92 Ϯ 1.62; P Ͻ 0.05). In conclusion, CFR can be significantly increased in CAD by a systemic infusion of L-NMMA. Similarly to our previous findings in normal volunteers, this suggests that adenosine-induced hyperemia in CAD patients is constrained by a mechanism that can be relieved by systemic NOS inhibition with L-NMMA. coronary circulation; autonomic nervous system; ischemic heart disease; cardiac imaging; positron emission tomography IT IS WELL ESTABLISHED THAT myocardial ischemia is a powerful stimulus for vasodilatation of coronary resistive vessels. The vasodilator response is reported to be near maximal for ischemic times of up to 15-20 s, while no further changes are observed for longer ischemic times (16).Experimental studies in animals have proven that intracoronary or intravenous infusion of adenosine achieves a degree of coronary vasodilatation comparable to that obtained after a period of ischemia of 15-20 s. In normal humans, intravenous infusion of 140 g/kg adenosine produces an increase in myocardial blood flow (MBF) approximately fourfold above the resting value with no further increase at higher adenosine doses (12,29).In a recent study in normal volunteers (15), we demonstrated that hyperemic MBF measured during the combined intravenous infusion of adenosine (140 g/kg) and the nitric oxide synthase (NOS) inhibitor N G -monomethyl-L-arginine (L-NMMA; 10 mg/ kg) was 53% higher than that during infusion of adenosine alone. This effect seems to necessitate an intact cardiac innervation, since no increase in MBF during ...

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Section: Discussionmentioning

confidence: 99%

Systemic nitric oxide synthase inhibition improves coronary flow reserve to adenosine in patients with significant stenoses

Kaufmann

Rimoldi

Gnecchi‐Ruscone

et al. 2007

American Journal of Physiology-Heart and Circulatory Physiology

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“…The close coupling of coronary blood flow and myocardial O 2 demand has been proposed to depend primarily on messengers released from the myocardium and endothelium but is also modulated by the autononomic nervous system. 1,2 Thus, in dogs, the treadmill exercise-induced increases in coronary blood flow and, hence, O 2 delivery do not fully match the increase in myocardial O 2 demand, so that even at mild to moderate levels of exercise (Ͻ70% of maximum heart rate), myocardial O 2 extraction increases [3][4][5][6][7] and cvPO 2 decreases. 5,[7][8][9] The decrease in cvPO 2 may represent a metabolic error signal needed for a negative-feedback control mechanism 1,10 but is at least in part due to ␣-adrenergic vasoconstriction of coronary resistance vessels.…”

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confidence: 99%

“…1,2 Thus, in dogs, the treadmill exercise-induced increases in coronary blood flow and, hence, O 2 delivery do not fully match the increase in myocardial O 2 demand, so that even at mild to moderate levels of exercise (Ͻ70% of maximum heart rate), myocardial O 2 extraction increases [3][4][5][6][7] and cvPO 2 decreases. 5,[7][8][9] The decrease in cvPO 2 may represent a metabolic error signal needed for a negative-feedback control mechanism 1,10 but is at least in part due to ␣-adrenergic vasoconstriction of coronary resistance vessels. 7,9,11 Conversely, the increase in sympathetic nerve activity during exercise also results in ␤-adrenergic coronary vasodilation, 5,12 which acts in a "feed-forward control" manner (ie, an open-loop control system that does not require an error signal 13,14 ) to blunt the ␣-adrenergic vasoconstriction in dogs.…”

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confidence: 99%

“…5,[7][8][9] The decrease in cvPO 2 may represent a metabolic error signal needed for a negative-feedback control mechanism 1,10 but is at least in part due to ␣-adrenergic vasoconstriction of coronary resistance vessels. 7,9,11 Conversely, the increase in sympathetic nerve activity during exercise also results in ␤-adrenergic coronary vasodilation, 5,12 which acts in a "feed-forward control" manner (ie, an open-loop control system that does not require an error signal 13,14 ) to blunt the ␣-adrenergic vasoconstriction in dogs.…”

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Autonomic Control of Vasomotion in the Porcine Coronary Circulation During Treadmill Exercise

Duncker

Stubenitsky

Verdouw

1998

Circulation Research

110

159

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Abstract-To date, no studies have investigated coronary vasomotor control of myocardial O 2 delivery (MDO 2 ) and its modulation by the autonomic nervous system in the porcine heart during treadmill exercise. We studied 8 chronically instrumented swine under resting conditions and during graded treadmill exercise. Exercise up to 85% to 90% of maximum heart rate produced an increase in myocardial O 2 consumption (MV O 2 ) from 163Ϯ16 mol/min (meanϮSE) at rest to 423Ϯ75 mol/min (PՅ0.05), which was paralleled by an increase in MDO 2 , so that myocardial O 2 extraction (79Ϯ1% at rest) and coronary venous O 2 tension (cvPO 2 , 23.7Ϯ1.0 mm Hg at rest) were maintained. ␤-Adrenoceptor blockade blunted the exercise-induced increase of MDO 2 out of proportion compared with the attenuation of the exercise-induced increase in MV O 2 , so that O 2 extraction rose from 78Ϯ1% at rest to 83Ϯ1% during exercise and cvPO 2 fell from 23.5Ϯ0.9 to 19.6Ϯ1.1 mm Hg (both PՅ0.05). In contrast, ␣-adrenoceptor blockade, either in the absence or presence of ␤-adrenoceptor blockade, had no effect on myocardial O 2 extraction or cvPO 2 at rest or during exercise. Muscarinic receptor blockade resulted in a decreased O 2 extraction and an increase in cvPO 2 at rest, an effect that waned during exercise. The vasodilation produced by muscarinic receptor blockade was likely due to an increased ␤-adrenoceptor activity, since combined muscarinic and ␤-adrenoceptor blockade produced similar changes in O 2 extraction and cvPO 2 , as did ␤-adrenoceptor blockade alone. In conclusion, in swine myocardium, MV O 2 and MDO 2 are matched during exercise, which is the result of feed-forward ␤-adrenergic vasodilation in conjunction with minimal ␣-adrenergic vasoconstriction. ␤-Adrenergic vasodilation is due to an increase in sympathetic activity but may also be supported by withdrawal of muscarinic receptor-mediated inhibition of ␤-adrenergic coronary vasodilation. The observation that cvPO 2 levels are maintained even during heavy exercise suggests that a decrease in cvPO 2 is not essential for coronary vasodilation during exercise. (Circ Res. 1998;82:1312-1322.)

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“…SYMPATHETIC coronary vasoconstriction has been observed in a number of laboratories (Szentivanyi and Juhasz-Nagy, 1959;Berne et al, 1965;Granata et al, 1965;Feigl, 1967;Ross, 1976), is of the areceptor type (Feigl, 1967;Pitt et al, 1967;McRaven et al, 1971;Gewirtz et al, 1982;Gwirtz and Stone, 1982;Macho et al, 1982), and is capable of competing with metabolic vasodilation (Mohrman and Feigl, 1978;Murray and Vatner, 1979;Gwirtz and Stone, 1982;Heyndrickx et al, 1982).…”

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Effect of coronary artery pressure on transmural distribution of adrenergic coronary vasoconstriction in the dog.

Buffington¹,

Feigl²

1983

Circulation Research

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SUMMARY. The transmural distribution of a-receptor coronary vasoconstriction was studied in 14 closed-chest, morphine-and chloralose-anesthesized dogs. The a-receptor-blocking agent, phenoxybenzamine (0.25 mg/kg), was infused into either the anterior or circumflex coronary artery while collection of coronary sinus blood mimimized recirculation. The left main coronary artery was cannulated and perfused at constant pressure. Myocardial lactate extraction and blood flow (9 nm radioactive microspheres) were measured during adrenergic activation with intracoronary norepinephrine (2 jig/min) at coronary artery pressures of 100, 70, 50, and 38 mm Hg. Flow was 15-25% less in the control region (a-receptors intact) than in the a-receptor-blocked region, in all layers of the left ventricular wall, at coronary pressures of 100 and 70 mm Hg. When coronary pressure was 50 mm Hg, lactate production resulted (-4% extraction) and significant a-receptor vasoconstriction was observed in the outer layer, but was marginal (P = 0.043) in the inner layer, of the left ventricle. Flows were not different in control and a-receptorblocked regions at a coronary pressure of 38 mm Hg (lactate extraction -49%). These data indicate a uniform transmural a-receptor vasoconstriction at normal coronary artery pressures that diminished as the heart was progressively underperfused. (Circ Res 53: 613-621, 1983)

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alpha-Adrenergic control of oxygen delivery to myocardium during exercise in conscious dogs

Cited by 44 publications

References 0 publications

Systemic nitric oxide synthase inhibition improves coronary flow reserve to adenosine in patients with significant stenoses

Systemic nitric oxide synthase inhibition improves coronary flow reserve to adenosine in patients with significant stenoses

Autonomic Control of Vasomotion in the Porcine Coronary Circulation During Treadmill Exercise

Effect of coronary artery pressure on transmural distribution of adrenergic coronary vasoconstriction in the dog.

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