Beta-adrenergic receptor blockade impairs NO-dependent dilation of large coronary arteries during exercise.
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 beta-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 beta-adrenergic receptor activation are required to cause CD dilation during exercise. Suppression of beta-adrenergic receptor activation leads to impaired shear stress-dependent NO formation and allows alpha-adrenergic constriction to become dominant.
Okajima
Masaki
M
Institut de Cardiologie de Montréal and Department of Physiology, Faculty of Medicine, Université de Montréal, Québec, Canada H1T 1C8.
Takamura
Masayuki
M
Véquaud
Philippe
P
Parent
Robert
R
Lavallée
Michel
M
D000241:Adenosine / Q000008:administration & dosage / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D001158:Arteries; D003331:Coronary Vessels / Q000502:physiology*; D004285:Dogs; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects; D007269:Injections, Intra-Arterial; D009043:Motor Activity / Q000502:physiology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D019335:Nitroarginine / Q000494:pharmacology; D005996:Nitroglycerin / Q000008:administration & dosage / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology*
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D004791:Enzyme Inhibitors; D019335:Nitroarginine; D009569:Nitric Oxide; D011433:Propranolol; D005996:Nitroglycerin; D000241:Adenosine; D019331:NG-Nitroarginine Methyl Ester