Endothelial release of nitric oxide contributes to the vasodilator effect of adenosine in humans

Paul Smits, Stephen Williams, Deborah E. Lipson, Peter Banitt, Gerard A. Rongen, Mark A. Creager

Research output: Contribution to journalArticle

Abstract

Background: The endogenous nucleoside adenosine plays an important role in the regulation of vascular tone, especially during ischemia. Experimental data derived from animal models suggest that nitric oxide (NO) contributes to the vasodilator effect of adenosine. The primary purpose of this investigation was to determine whether the endothelial release of NO contributes to adenosine-induced vasodilation in humans. Methods and Results: Venous occlusion plethysmography was used to assess the forearm blood flow (FBF) responses to graded intra-arterial infusions of adenosine (1.5 to 500 μg/min). Dose-response curves were constructed before and during intra- arterial infusion of the NO synthase inhibitor N(G)-monomethyl-L-arginine (L- NMMA) (2 mg/min, n=6) or vehicle (n=6). Before infusion of L-NMMA, adenosine caused a dose-dependent increase in FBF from 2.3 to 15.9 mL · min-1 · dL-1. During concurrent infusion of L-NMMA, adenosine increased FBF from 1.7 to 10.0 mL · min-1 · dL-1, and this change from baseline was significantly reduced compared with that before L-NMMA (P-1 · dL-1 before L-NMMA and from 1.3 to 13.6 mL · min- 1 · dL-1 during L-NMMA; n=6, P=NS). The second objective of this study was to determine whether the adenosine-induced release of NO is mediated by activation of endothelial potassium channels, putatively coupled to adenosine receptors. Thus, the FBF response to adenosine was measured before and during infusion of the ATP-dependent potassium channel blocker tolbutamide (1 mg/min, n=6), or the potassium channel blocker quinidine (0.5 mg/min, n=6). The adenosine-mediated increments in FBF were not attenuated by either potassium channel blocker. Conclusions: Adenosine-induced vasodilation in humans is mediated, at least in part, by endothelial release of NO. The transducing mechanism of this phenomenon is not known, but it does not appear to involve the activation of either ATP-dependent or quinidine-sensitive potassium channels.

Original languageEnglish (US)
Pages (from-to)2135-2141
Number of pages7
JournalCirculation
Volume92
Issue number8
StatePublished - Oct 15 1995
Externally publishedYes

Fingerprint

Vasodilator Agents
Adenosine
Nitric Oxide
omega-N-Methylarginine
Forearm
Potassium Channel Blockers
Intra Arterial Infusions
Quinidine
Potassium Channels
Vasodilation
Adenosine Triphosphate
Tolbutamide
Purinergic P1 Receptors
Plethysmography
Nucleosides
Nitric Oxide Synthase
Blood Vessels
Arginine
Ischemia
Animal Models

Keywords

  • adenosine
  • endothelium
  • nitric oxide
  • vasodilation

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Smits, P., Williams, S., Lipson, D. E., Banitt, P., Rongen, G. A., & Creager, M. A. (1995). Endothelial release of nitric oxide contributes to the vasodilator effect of adenosine in humans. Circulation, 92(8), 2135-2141.

Endothelial release of nitric oxide contributes to the vasodilator effect of adenosine in humans. / Smits, Paul; Williams, Stephen; Lipson, Deborah E.; Banitt, Peter; Rongen, Gerard A.; Creager, Mark A.

In: Circulation, Vol. 92, No. 8, 15.10.1995, p. 2135-2141.

Research output: Contribution to journalArticle

Smits, P, Williams, S, Lipson, DE, Banitt, P, Rongen, GA & Creager, MA 1995, 'Endothelial release of nitric oxide contributes to the vasodilator effect of adenosine in humans', Circulation, vol. 92, no. 8, pp. 2135-2141.
Smits P, Williams S, Lipson DE, Banitt P, Rongen GA, Creager MA. Endothelial release of nitric oxide contributes to the vasodilator effect of adenosine in humans. Circulation. 1995 Oct 15;92(8):2135-2141.
Smits, Paul ; Williams, Stephen ; Lipson, Deborah E. ; Banitt, Peter ; Rongen, Gerard A. ; Creager, Mark A. / Endothelial release of nitric oxide contributes to the vasodilator effect of adenosine in humans. In: Circulation. 1995 ; Vol. 92, No. 8. pp. 2135-2141.
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abstract = "Background: The endogenous nucleoside adenosine plays an important role in the regulation of vascular tone, especially during ischemia. Experimental data derived from animal models suggest that nitric oxide (NO) contributes to the vasodilator effect of adenosine. The primary purpose of this investigation was to determine whether the endothelial release of NO contributes to adenosine-induced vasodilation in humans. Methods and Results: Venous occlusion plethysmography was used to assess the forearm blood flow (FBF) responses to graded intra-arterial infusions of adenosine (1.5 to 500 μg/min). Dose-response curves were constructed before and during intra- arterial infusion of the NO synthase inhibitor N(G)-monomethyl-L-arginine (L- NMMA) (2 mg/min, n=6) or vehicle (n=6). Before infusion of L-NMMA, adenosine caused a dose-dependent increase in FBF from 2.3 to 15.9 mL · min-1 · dL-1. During concurrent infusion of L-NMMA, adenosine increased FBF from 1.7 to 10.0 mL · min-1 · dL-1, and this change from baseline was significantly reduced compared with that before L-NMMA (P-1 · dL-1 before L-NMMA and from 1.3 to 13.6 mL · min- 1 · dL-1 during L-NMMA; n=6, P=NS). The second objective of this study was to determine whether the adenosine-induced release of NO is mediated by activation of endothelial potassium channels, putatively coupled to adenosine receptors. Thus, the FBF response to adenosine was measured before and during infusion of the ATP-dependent potassium channel blocker tolbutamide (1 mg/min, n=6), or the potassium channel blocker quinidine (0.5 mg/min, n=6). The adenosine-mediated increments in FBF were not attenuated by either potassium channel blocker. Conclusions: Adenosine-induced vasodilation in humans is mediated, at least in part, by endothelial release of NO. The transducing mechanism of this phenomenon is not known, but it does not appear to involve the activation of either ATP-dependent or quinidine-sensitive potassium channels.",
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AU - Smits, Paul

AU - Williams, Stephen

AU - Lipson, Deborah E.

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AU - Rongen, Gerard A.

AU - Creager, Mark A.

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N2 - Background: The endogenous nucleoside adenosine plays an important role in the regulation of vascular tone, especially during ischemia. Experimental data derived from animal models suggest that nitric oxide (NO) contributes to the vasodilator effect of adenosine. The primary purpose of this investigation was to determine whether the endothelial release of NO contributes to adenosine-induced vasodilation in humans. Methods and Results: Venous occlusion plethysmography was used to assess the forearm blood flow (FBF) responses to graded intra-arterial infusions of adenosine (1.5 to 500 μg/min). Dose-response curves were constructed before and during intra- arterial infusion of the NO synthase inhibitor N(G)-monomethyl-L-arginine (L- NMMA) (2 mg/min, n=6) or vehicle (n=6). Before infusion of L-NMMA, adenosine caused a dose-dependent increase in FBF from 2.3 to 15.9 mL · min-1 · dL-1. During concurrent infusion of L-NMMA, adenosine increased FBF from 1.7 to 10.0 mL · min-1 · dL-1, and this change from baseline was significantly reduced compared with that before L-NMMA (P-1 · dL-1 before L-NMMA and from 1.3 to 13.6 mL · min- 1 · dL-1 during L-NMMA; n=6, P=NS). The second objective of this study was to determine whether the adenosine-induced release of NO is mediated by activation of endothelial potassium channels, putatively coupled to adenosine receptors. Thus, the FBF response to adenosine was measured before and during infusion of the ATP-dependent potassium channel blocker tolbutamide (1 mg/min, n=6), or the potassium channel blocker quinidine (0.5 mg/min, n=6). The adenosine-mediated increments in FBF were not attenuated by either potassium channel blocker. Conclusions: Adenosine-induced vasodilation in humans is mediated, at least in part, by endothelial release of NO. The transducing mechanism of this phenomenon is not known, but it does not appear to involve the activation of either ATP-dependent or quinidine-sensitive potassium channels.

AB - Background: The endogenous nucleoside adenosine plays an important role in the regulation of vascular tone, especially during ischemia. Experimental data derived from animal models suggest that nitric oxide (NO) contributes to the vasodilator effect of adenosine. The primary purpose of this investigation was to determine whether the endothelial release of NO contributes to adenosine-induced vasodilation in humans. Methods and Results: Venous occlusion plethysmography was used to assess the forearm blood flow (FBF) responses to graded intra-arterial infusions of adenosine (1.5 to 500 μg/min). Dose-response curves were constructed before and during intra- arterial infusion of the NO synthase inhibitor N(G)-monomethyl-L-arginine (L- NMMA) (2 mg/min, n=6) or vehicle (n=6). Before infusion of L-NMMA, adenosine caused a dose-dependent increase in FBF from 2.3 to 15.9 mL · min-1 · dL-1. During concurrent infusion of L-NMMA, adenosine increased FBF from 1.7 to 10.0 mL · min-1 · dL-1, and this change from baseline was significantly reduced compared with that before L-NMMA (P-1 · dL-1 before L-NMMA and from 1.3 to 13.6 mL · min- 1 · dL-1 during L-NMMA; n=6, P=NS). The second objective of this study was to determine whether the adenosine-induced release of NO is mediated by activation of endothelial potassium channels, putatively coupled to adenosine receptors. Thus, the FBF response to adenosine was measured before and during infusion of the ATP-dependent potassium channel blocker tolbutamide (1 mg/min, n=6), or the potassium channel blocker quinidine (0.5 mg/min, n=6). The adenosine-mediated increments in FBF were not attenuated by either potassium channel blocker. Conclusions: Adenosine-induced vasodilation in humans is mediated, at least in part, by endothelial release of NO. The transducing mechanism of this phenomenon is not known, but it does not appear to involve the activation of either ATP-dependent or quinidine-sensitive potassium channels.

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