Beta 2-adrenergic dilation of conductance coronary arteries involves flow-dependent NO formation in conscious dogs.
The contribution of nitric oxide (NO) formation to the dilation of large epicardial coronary arteries to beta 1- and beta 2-adrenergic receptor stimulation was investigated in conscious dogs. After beta 1-adrenergic blockade (atenolol, 1.0 mg/kg iv), selective beta 2-adrenergic receptor activation with intracoronary bolus injections of pirbuterol (50 ng/kg) increased coronary blood flow (CBF) by 95 +/- 19% from 48.5 +/- 8.4 ml/min and external epicardial coronary diameter (CD) by 0.14 +/- 0.03 from 3.23 +/- 0.31 mm. After intracoronary N omega-nitro-L-arginine methyl ester (L-NAME, 50 micrograms.kg-1.min-1 x 12 min) was administered, baseline CD decreased but CBF was not altered. After L-NAME, bolus injections of pirbuterol resulted in smaller (P < 0.01) CBF responses (40 +/- 12%), and increases in CD were abolished. When pirbuterol (500 ng.kg-1.min-1) was given as a continuous infusion, CBF increased by 36 +/- 5% from 55.4 +/- 5.8 ml/min and CD by 0.16 +/- 0.03 mm from 3.44 +/- 0.16 mm. L-NAME abolished CD increases and limited (P < 0.01) CBF responses to 9 +/- 3%. When increases in CBF caused by pirbuterol before L-NAME were prevented by arterial constriction, CD increases were suppressed. In contrast, CBF and CD responses to beta 1-adrenergic stimulation were maintained after L-NAME. Thus beta 2-adrenergic dilation of epicardial conductance arteries is primarily a flow-dependent process involving NO formation. In contrast, beta 1-adrenergic activation produces epicardial coronary dilation independent of an L-NAME-sensitive mechanism.
Hamdad
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Department of Physiology, Faculty of Medicine, Université de Montréal, Québec, Canada.
Ming
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Parent
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Lavallée
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D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001158:Arteries / Q000502:physiology; D003326:Coronary Circulation / Q000187:drug effects / Q000502:physiology*; D003327:Coronary Disease / Q000503:physiopathology; D003331:Coronary Vessels / Q000502:physiology*; D004285:Dogs; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006706:Homeostasis; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis*; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D014664:Vasodilation / Q000502:physiology*
D000319:Adrenergic beta-Antagonists; D004791:Enzyme Inhibitors; D011943:Receptors, Adrenergic, beta; D009569:Nitric Oxide; D019331:NG-Nitroarginine Methyl Ester