β-Adrenergic receptor blockade impairs NO-dependent dilation of large coronary arteries during exercise

2003 ◽  
Vol 284 (2) ◽  
pp. H501-H510 ◽  
Author(s):  
Masaki Okajima ◽  
Masayuki Takamura ◽  
Philippe Véquaud ◽  
Robert Parent ◽  
Michel Lavallée
Keyword(s):  
Shear Stress ◽  
Coronary Arteries ◽  
Adrenergic Receptor ◽  
Receptor Activation ◽  
Receptor Blockade ◽  
External Diameter ◽  
No Formation ◽  
Exercise Induced ◽  
Stress Dependent ◽  
Adrenergic Receptor Blockade

Shear stress-dependent nitric oxide (NO) formation prevents immoderate vascular constriction. We examined whether shear stress-dependent NO formation limits exercise-induced coronary artery constriction after β-adrenergic receptor blockade in dogs. Control exercise led to increases ( P < 0.01) in coronary blood flow (CBF) by 38 ± 5 ml/min from 41 ± 5 ml/min and in the external diameter of epicardial coronary arteries (CD) by 0.24 ± 0.03 mm from 3.33 ± 0.20 mm. CD and shear stress were linearly related. After propranolol, CD fell ( P < 0.01) during exercise (0.08 ± 0.03 from 3.23 ± 0.19 mm), and the slope of the relationship between CD and shear stress was reduced ( P< 0.01). This slope was not further altered by the additional blockade of NO formation. In propranolol-treated resting dogs, flow-dependent effects of intracoronary adenosine to mimic exercise-induced increases in shear stress (after propranolol) led to increases ( P< 0.01) in CD (0.09 ± 0.02 from 3.68 ± 0.27 mm). Thus both shear stress-dependent NO formation and β-adrenergic receptor activation are required to cause CD dilation during exercise. Suppression of β-adrenergic receptor activation leads to impaired shear stress-dependent NO formation and allows α-adrenergic constriction to become dominant.

Enhanced contribution of NO to exercise-induced coronary responses after α-adrenergic receptor blockade

2002 ◽  
Vol 282 (2) ◽  
pp. H508-H515 ◽  
Author(s):  
Masayuki Takamura ◽  
Robert Parent ◽  
Michel Lavallée
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Methyl Ester ◽  
Adrenergic Receptors ◽  
Adrenergic Receptor ◽  
Receptor Blockade ◽  
No Formation ◽  
Exercise Induced ◽  
Adrenergic Effects ◽  
Adrenergic Receptor Blockade

We hypothesized that nitric oxide (NO), in addition to β-adrenergic effects, may contribute to exercise-induced coronary responses after α-adrenergic receptor blockade. Data were analyzed as relationships between coronary sinus (CS) O2 saturation (CS O2sat) or coronary blood flow (CBF) and myocardial O2 consumption (MV˙o 2). As MV˙o 2 increased, CS O2sat fell more ( P < 0.05) after N ω-nitro-l-arginine methyl ester (l-NAME; slope = −2.9 ± 0.4 × 10−2 %saturation · μl O2 · min−1 · g−1) than before (slope = −2.1 ± 0.3 × 10−2%saturation · μl O2 · min−1 · g−1). The slope of CBF versus MV˙o 2 was not altered. After blockade of α-adrenergic receptors alone (phentolamine), CS O2sat failed to decrease as MV˙o 2 increased (slope = −0.1 ± 0.5 × 10−2 %saturation · μl O2 · min−1 · g−1).l-NAME given after phentolamine led to substantial decreases in CS O2sat ( P < 0.01) as MV˙o 2 increased (slope = −2.1 ± 0.4 × 10−2 percent saturation · μl O2 −1 · min−1 · g−1). CBF responses to exercise were smaller ( P < 0.01) after phentolamine + l-NAME (slope = 6.1 ± 0.1 × 10−3 ml/μl O2) than after phentolamine alone (slope = 6.9 ± 0.2 × 10−3 ml/μl O2). Thus a significant portion of exercise-induced coronary responses after α-adrenergic receptor blockade involves NO formation.

Beta 2-adrenergic dilation of conductance coronary arteries involves flow-dependent NO formation in conscious dogs

1996 ◽  
Vol 271 (5) ◽  
pp. H1926-H1937 ◽  
Author(s):  
N. Hamdad ◽  
Z. Ming ◽  
R. Parent ◽  
M. Lavallee
Keyword(s):  
Coronary Arteries ◽  
Adrenergic Receptor ◽  
Receptor Activation ◽  
Conscious Dogs ◽  
Adrenergic Blockade ◽  
Adrenergic Stimulation ◽  
No Formation ◽  
Beta 2 ◽  
Arterial Constriction ◽  
Adrenergic Activation

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.

Contribution of endogenous endothelin to large epicardial coronary artery tone in dogs and humans

1999 ◽  
Vol 277 (2) ◽  
pp. H524-H532 ◽  
Author(s):  
Éric Thorin ◽  
Robert Parent ◽  
Zhi Ming ◽  
Michel Lavallée
Keyword(s):  
Coronary Artery ◽  
Coronary Arteries ◽  
Receptor Activation ◽  
Receptor Blockade ◽  
Circumflex Coronary Artery ◽  
No Formation ◽  
Inhibitory Feedback ◽  
Coronary Artery Diameter

Nitric oxide (NO) may normally impair endothelin (ET) activity in epicardial coronary arteries. Lifting this inhibitory feedback could reveal ET-dependent effects involving ETA- and/or ETB-receptor activation. In conscious dogs, the blockade of ETA receptors (intracoronary Ro-61–1790) increased external circumflex coronary artery diameter (CD) (sonomicrometry) by 0.10 ± 0.01 from 3.04 ± 0.12 mm ( P < 0.01) without altering coronary blood flow (Doppler). Similarly, CD increased (0.09 ± 0.01 from 2.91 ± 0.14 mm; P < 0.01) when Ro-61–1790 was given after blockade of NO formation with intracoronary N ω-nitro-l-arginine methyl ester (l-NAME). In contrast, ETB-receptor blockade (intracoronary Ro-46–8443) did not influence baseline CD with and without l-NAME. In vitro, increases in tension caused by N ω-nitro-l-arginine (l-NNA) or PGF2α in arterial rings were reduced by ETA- but not ETB-receptor blockade. ETA-receptor blockade also reduced the increase in tension caused byl-NNA in human coronary arterial rings. Thus ETA receptors, but not ETB receptors, account for ET-dependent constriction in canine epicardial coronary arteries in vivo. ET-dependent effects were independent of the level of NO formation in vitro and in vivo. In human epicardial coronary arterial rings, ETA-receptor blockade also caused significant relaxation.

Effect of β-Adrenergic Receptor Blockade on Blood Flow to Collateral-Dependent Myocardium During Exercise

Circulation ◽  
1995 ◽  
Vol 91 (5) ◽  
pp. 1560-1567 ◽  
Author(s):  
Jay H. Traverse ◽  
John D. Altman ◽  
James Kinn ◽  
Dirk J. Duncker ◽  
Robert J. Bache
Keyword(s):  
Blood Flow ◽  
Adrenergic Receptor ◽  
Receptor Blockade ◽  
Adrenergic Receptor Blockade
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