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

Abstract

Okajima, Masaki, Masayuki Takamura, Philippe Vé -quaud, Robert Parent, and Michel Lavallé e. ␤-Adrenergic receptor blockade impairs NO-dependent dilation of large coronary arteries during exercise. Am J Physiol Heart Circ Physiol 284: H501-H510, 2003. First published October 3, 2002 10.1152/ajpheart.00419.2002-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 ␤-adrenergic receptor blockade in dogs. Control exercise led to increases (P Ͻ 0.01) in coronary blood flow (CBF) by 38 Ϯ 5 ml/min from 41 Ϯ 5 ml/min and in the external diameter of epicardial coronary arteries (CD) by 0.24 Ϯ 0.03 mm from 3.33 Ϯ 0.20 mm. CD and shear stress were linearly related. After propranolol, CD fell (P Ͻ 0.01) during exercise (0.08 Ϯ 0.03 from 3.23 Ϯ 0.19 mm), and the slope of the relationship between CD and shear stress was reduced (P Ͻ 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 Ͻ 0.01) in CD (0.09 Ϯ 0.02 from 3.68 Ϯ 0.27 mm). Thus both shear stress-dependent NO formation and ␤-adrenergic receptor activation are required to cause CD dilation during exercise. Suppression of ␤-adrenergic receptor activation leads to impaired shear stress-dependent NO formation and allows ␣-adrenergic constriction to become dominant. nitric oxide; adrenergic receptors; endothelium; shear stress; coronary vessels NITRIC OXIDE (NO) and ␤-adrenergic receptor activation are the major determinants of large epicardial coronary artery dilation during exercise. In those vessels, endothelium-derived NO formation during exercise is a flow-dependent process, secondary to increases in shear stress (20). Preventing the rise in coronary blood flow (CBF) (20), endothelial denudation (3), or blockade of NO formation (27) blunts large epicardial coronary dilation. Therefore, NO-dependent dilation of conductance coronary arteries during exercise may be considered as a secondary phenomenon triggered by the dilation of resistance coronary vessels. In addition to NO, ␤-adrenergic receptors directly contribute to conductance vessel dilation during exercise, because their blockade leads to a paradoxical constriction sensitive to ␣-adrenergic receptor blockade (2). In resistance vessels, ␤-adrenergic receptor activation causes dilator responses during exercise and serves as a feedforward mechanism (10, 11). In contrast, NO is not essential for increasing CBF and ensuring a close match between myocardial oxygen supply and demand during exercise (1,4,24,25).One intriguing observation is the complete failure of the large epicardial coronary artery to dilate during exercise performed after ␤-adrenergic receptor blockade (2). Despite the elevated shear stress caused by the decrease in large epicardial coro...

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