Endothelial Release of Nitric Oxide Contributes to the Vasodilator Effect of Adenosine in Humans

Smits, P.; Williams, Stephen B.; Lipson, D.; Banitt, Peter F.; Rongen, Gerard A.; Creager, Mark A.

doi:10.1161/01.cir.92.8.2135

Cited by 212 publications

(158 citation statements)

References 44 publications

(9 reference statements)

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“…33,34 However, we did not detect any diminution of coronary flow reserve with L-NMMA. CBF estimation was based on the assumption that adenosine does not significantly affect conduit vessel dimensions within the 15 to 20 seconds taken for maximum vasodilation.…”

Section: Response To Adenosinecontrasting

confidence: 63%

Contribution of Vasodilator Prostanoids and Nitric Oxide to Resting Flow, Metabolic Vasodilation, and Flow-Mediated Dilation in Human Coronary Circulation

et al. 1999

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Background-Endothelial dysfunction is associated with atherosclerosis and may contribute to ischemic syndromes. We assessed the contribution of endothelium-derived nitric oxide (NO) and vasodilator prostanoids to resting blood flow, metabolic vasodilation, and flow reserve in the human coronary circulation. Methods and Results-Coronary hemodynamics were assessed before and after inhibition of vasodilator prostanoids and NO with intracoronary aspirin (acetylsalicylic acid [ASA]) and N

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Section: Response To Adenosinecontrasting

confidence: 63%

Contribution of Vasodilator Prostanoids and Nitric Oxide to Resting Flow, Metabolic Vasodilation, and Flow-Mediated Dilation in Human Coronary Circulation

et al. 1999

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“…Animal studies are in disagreement about the ability of adenosine to induce NO release; studies in favor and against have been reported, and this may depend on the vascular bed and species studied. In the human forearm, adenosine-induced vasodilation was attenuated in the presence of the NOS inhibitor L-NMMA in one study 29 but not in another. 30 Adenosine-induced coronary vasodilation is believed to be independent of NO release in humans, 31 and intracoronary adenosine is routinely used as an indicator of endothelium-independent coronary vasodilation.…”

Section: Discussionmentioning

confidence: 86%

Blockade of Nucleoside Transport Is Required for Delivery of Intraarterial Adenosine Into the Interstitium

et al. 2003

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Background-Adenosine, a known mediator of preconditioning, has been infused into the coronary circulation to induce therapeutic preconditioning, eg, in preparation for angioplasty. However, results have been disappointing. We tested the hypothesis that endothelial nucleoside transporter acts as a barrier impeding the delivery of intravascular adenosine into the underlying myocardium and that this can be overcome with dipyridamole, a nucleoside transporter blocker. Methods and Results-We infused saline or adenosine (0.125 and 0.5 mg/min) into the brachial artery while monitoring forearm blood flow (FBF) and interstitial adenosine levels with microdialysis probes implanted in the flexor digitorum superficialis of the forearm in 7 healthy volunteers during intravenous administration of saline or dipyridamole (loading dose, 0.142 mg/kg per min for 5 minutes followed by 0.004 mg/kg per min). Adenosine produced near maximal forearm vasodilation, increasing FBF from 4.0Ϯ0.7 to 10.4Ϯ1.9 and 13.1Ϯ1.6 mL/100 mL per min for the low and high doses, respectively, but did not increase muscle dialysate adenosine concentration (from 88Ϯ21 to 65Ϯ23 and 85Ϯ26 nmol/L). Intravenous dipyridamole enhanced resting muscle dialysate adenosine (from 77Ϯ25 to 147Ϯ50 nmol/L), adenosineinduced increase in FBF (from 4.1Ϯ0.8 to 12.6Ϯ3 and 15.1Ϯ3 mL/100 mL per min for the low and high dose, respectively), and the delivery of adenosine into the interstitium (to 290Ϯ80 and 299Ϯ143 nmol/L for the low and high dose, respectively, Pϭ0.04). Key Words: adenosine Ⅲ ischemia Ⅲ endothelium Ⅲ blood flow A denosine is an intermediate product in the breakdown of ATP and accumulates in the interstitium of metabolically active tissues when oxygen demands exceed supply, eg, during ischemia. 1,2 Adenosine is considered a retaliatory autacoid, whose main function is to protect tissues against ischemia-related injury. Many of its actions are indeed consistent with such a role. Adenosine contributes to reactive hyperemia and produces maximal coronary vasodilation, inhibits norepinephrine and renin release, and inhibits neutrophil activation and platelet aggregation. Conclusions-IntravascularAdenosine is also considered an important mediator of ischemic preconditioning, a phenomenon by which an initial brief period of ischemia protects the tissue from the damage produced by a subsequent more intense ischemic episode. It is believed that during transient coronary occlusion, adenosine and other mediators are released and initiate a cascade of intracellular events involving protein kinase C activation that are responsible for the protective effect to subsequent ischemia. [3][4][5][6] There has been interest, therefore, in replicating ischemic preconditioning by infusing adenosine and using this pharmacological preconditioning as a therapeutic approach for cardiac protection. A situation where this approach may be of practical relevance is angioplasty, where ischemia may be induced transiently during the procedure. Indeed, adenosine has been infused into the coronary ...

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“…Flow-mediated dilation has been proposed to represent a functional bioassay for endothelium-derived NO bioavailability in humans 6 , as vasodilation occurs via NO release from the endothelium in response to increased shear rate 1,3 . Thus, a higher FMD normalized to peak shear rate represents an endothelium that has increased sensitivity a given increase in shear rate.…”

Section: Discussionmentioning

confidence: 99%

“…There are numerous molecules released from the endothelium that result in modulation of blood vessel diameter. Among these molecules, nitric oxide (NO), appears to be the primary vasodilatory molecule released from the vascular endothelium in response to stimulation (e.g., insulin, acetylcholine, or changes in shear stress) 1 . In the vascular endothelium, NO is produced by the enzyme endothelial NO synthase (eNOS) and is subsequently released from endothelial cells 2 .…”

Section: Introductionmentioning

confidence: 99%

Ultrasound Assessment of Flow-Mediated Dilation of the Brachial and Superficial Femoral Arteries in Rats

Machin

Leary

et al. 2016

JoVE

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Arterial vasodilation to increases in wall shear rate is indicative of vascular endothelial function. In humans, the non-invasive measurement of endothelial function can be achieved by employing the flow-mediated dilation technique, typically performed in the brachial or superficial femoral artery. Briefly, a blood pressure cuff placed distal to an ultrasound probe is inflated to a suprasystolic pressure, which results in limb ischemia. After 5 min of occlusion the cuff is deflated, resulting in reactive hyperemia and increases in wall shear rate that signal vasodilatory molecules to be released from the endothelium eliciting vasodilation. Despite the thousands of studies performing flow-mediated dilation in humans, surprisingly, no studies have performed this technique non-invasively in living rats. Considering the recent shift in focus to translational research, the establishment of guidelines for non-invasive measurement of flow-mediated dilation in rats and other rodents would be extremely valuable. In the following article, a protocol is presented for the non-invasive measurement of flow-mediated dilation in brachial and superficial femoral arteries of rats, as those sites are most commonly measured in humans. Video LinkThe video component of this article can be found at

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Endothelial Release of Nitric Oxide Contributes to the Vasodilator Effect of Adenosine in Humans

Cited by 212 publications

References 44 publications

Contribution of Vasodilator Prostanoids and Nitric Oxide to Resting Flow, Metabolic Vasodilation, and Flow-Mediated Dilation in Human Coronary Circulation

Contribution of Vasodilator Prostanoids and Nitric Oxide to Resting Flow, Metabolic Vasodilation, and Flow-Mediated Dilation in Human Coronary Circulation

Blockade of Nucleoside Transport Is Required for Delivery of Intraarterial Adenosine Into the Interstitium

Ultrasound Assessment of Flow-Mediated Dilation of the Brachial and Superficial Femoral Arteries in Rats

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