Coronary flow during exercise after selective alpha 1- and alpha 2-adrenergic blockade

Dai, Xue-Zheng; Sublett, E.; Lindstrom, Paul; Schwartz, J. Sanford; Homans, D. C.; Bache, Robert J.

doi:10.1152/ajpheart.1989.256.4.h1148

Cited by 20 publications

(21 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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“…This point is illustrated in Figure 26 wherein a significant increase in the slope of the relationship between coronary blood flow and MVO 2 is observed following α-adrenoceptor inhibition, which is accompanied by a flattening (decrease) in the slope of the coronary venous PO 2 versus MVO 2 relationship (389). Although both α 1 - and α 2 -adrenoceptors can produce coronary vasoconstriction, adrenergic constriction appears to primarily involve α 1 adrenoceptors (215, 888). In contrast, minimal changes in coronary blood flow or coronary venous PO 2 are observed following α-adrenoceptor blockade in exercising swine (280, 840).…”

Section: Neural Controlmentioning

confidence: 99%

Regulation of Coronary Blood Flow

Goodwill

Dick

Kiel

et al. 2017

Comprehensive Physiology

221

248

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The heart is uniquely responsible for providing its own blood supply through the coronary circulation. Regulation of coronary blood flow is quite complex and, after over 100 years of dedicated research, is understood to be dictated through multiple mechanisms that include extravascular compressive forces (tissue pressure), coronary perfusion pressure, myogenic, local metabolic, endothelial as well as neural and hormonal influences. While each of these determinants can have profound influence over myocardial perfusion, largely through effects on end-effector ion channels, these mechanisms collectively modulate coronary vascular resistance and act to ensure that the myocardial requirements for oxygen and substrates are adequately provided by the coronary circulation. The purpose of this series of Comprehensive Physiology is to highlight current knowledge regarding the physiologic regulation of coronary blood flow, with emphasis on functional anatomy and the interplay between the physical and biological determinants of myocardial oxygen delivery.

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“…In the latter study, systemic AT 1 blockade was associated with an increase in heart rate suggestive of baroreflex-mediated activation of sympathetic activity. Because in the dog norepinephrine produces coronary vasoconstriction via ␣-adrenoceptors (4,11), the direct coronary vasodilation produced by AT 1 receptor blockade may have been masked by an increased ␣-adrenergic vasoconstrictor influence. Fig.…”

Section: Effect Of Endogenous Angiotensin II On Coronary Vasomotor Tomentioning

confidence: 99%

Coronary vasoconstrictor influence of angiotensin II is reduced in remodeled myocardium after myocardial infarction

Merkus¹,

Haitsma²,

Sorop³

et al. 2006

American Journal of Physiology-Heart and Circulatory Physiology

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The renin-angiotensin system plays an important role in cardiovascular homeostasis by contributing to the regulation of blood volume, blood pressure, and vascular tone. Because AT(1) receptors have been described in the coronary microcirculation, we investigated whether ANG II contributes to the regulation of coronary vascular tone and whether its contribution is altered during exercise. Since the renin-angiotensin system is activated after myocardial infarction, resulting in an increase in circulating ANG II, we also investigated whether the contribution of ANG II to the regulation of vasomotor tone is altered after infarction. Twenty-six chronically instrumented swine were studied at rest and while running on a treadmill at 1-4 km/h. In 13 swine, myocardial infarction was induced by ligation of the left circumflex coronary artery. Blockade of AT(1) receptors (irbesartan, 1 mg/kg iv) had no effect on myocardial O(2) consumption but resulted in an increase in coronary venous O(2) tension and saturation both at rest and during exercise, reflecting coronary vasodilation. Despite increased plasma levels of ANG II after infarction and maintained coronary arteriolar AT(1) receptor levels, the vasodilation evoked by irbesartan was significantly reduced both at rest and during exercise. In conclusion, despite elevated plasma levels, the vasoconstrictor influence of ANG II on the coronary circulation in vivo is reduced after myocardial infarction. This reduction in ANG II-induced coronary vasoconstriction may serve to maintain perfusion of the remodeled myocardium.

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Coronary flow during exercise after selective alpha 1- and alpha 2-adrenergic blockade

Cited by 20 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

Regulation of Coronary Blood Flow

Coronary vasoconstrictor influence of angiotensin II is reduced in remodeled myocardium after myocardial infarction

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