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Communications to the Editor |

β-Blockers With Vasodilatory Actions FREE TO VIEW

Suranjan Mukherjee; Saumitra Baksi
Author and Funding Information

Affiliations: Royal Victoria Infirmary, Newcastle-upon-Tyne, UK,  Monklands Hospital, Glasgow, UK,  Marshfield Clinic, Marshfield, WI

Correspondence to: Suranjan Mukherjee, Royal Victoria Infirmary, Queen Victoria Rd, Newcastle-upon-Tyne, NE1 4LP, United Kingdom



Chest. 2003;124(4):1621. doi:10.1378/chest.124.4.1621
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To the Editor:

We have read with interest the article by Dart et al (January 2003)1 and would like to make few comments. The authors have grouped atenolol, labetalol, nebivolol, and doxazosin into a class of β-blockers with additional α-receptor-blocking action. It is known that labetalol, celiprolol, carvedilol, and nebivolol are β-blockers, but they also have an additional arteriolar vasodilating action. The mechanism by which they produce this action is diverse, whereas atenolol does not have any additional vasodilatory property. Labetalol and carvedilol (now called third-generation β-blockers) produce vasodilatation by their α- receptor-blocking effect. Labetalol has a higher affinity for α1 receptors than for β1 and β2 receptors, whereas carvedilol has twofold to threefold selectivity for β1 receptors vs α1 receptors.2 Nebivolol is a racemic mixture of d-enantiomers and l-enantiomers, and d-nebivolol is a highly selective β1-adrenergic receptor antagonist. In addition, nebivolol also produces direct vasorelaxation in humans and animals by endothelial β2-adrenergic receptor ligation with subsequent endothelial nitric oxide (NO) synthase-dependent NO production.4 This effect can be abolished by inhibitors of NO synthase.3

Studies about doxazosin show that it selectively blocks the postjunctional α1-adrenergic receptor, which is the primary mediator of the pressor effects of noradrenaline, thereby producing vasodilatation.5 However, there is also evidence of its interaction with adenosine receptors (adenosine, through its interaction with adenosine receptors, inhibits α1-adrenoceptor responses to various stimuli).,5 Some of the pharmacologic properties of doxazosin cannot be fully explained by its α-blocking effect, and a direct effect on adenosine receptors cannot be excluded.5

Dart, RA, Gollub, S, Lazar, J, et al (2003) Treatment of systemic hypertension in patients with pulmonary disease: COPD and asthma.Chest123,222-243. [CrossRef] [PubMed]
 
Bristow, MR Beta-adrenergic receptor blockade in chronic heart failure.Circulation2000;101,558-569. [CrossRef] [PubMed]
 
Broeders, MA, Doevendans, PA, Bekkers, BC, et al Nebivolol: a third generation beta-blocker that augments vascular nitric oxide release; endothelial beta (2)-adrenergic receptor- mediated nitric oxide production.Circulation2000;102,677-684. [CrossRef] [PubMed]
 
Van de Water, A, Janssens, W, Van Nueten, J, et al Pharmacological and hemodynamic profile of nebivolol, a chemically novel, potent, and selective beta 1-adrenergic antagonist.J Cardiovasc Pharmacol1988;11,552-563. [CrossRef] [PubMed]
 
Varani, K, Manfredini, R, Iannotta, V, et al Effects of doxazosin and propranolol on A2A adenosine receptors in essential hypertension.Hypertension2002;40,909-913. [CrossRef] [PubMed]
 
To the Editor:

Doctors Mukherjee and Baksi make very good points about these classes of antihypertensive medications. However, it was not the intent or design of this review to provide an in-depth commentary about the discrete or specific mechanisms of action of the various drugs. This was a direct result also of marked space limitations for our publication. Nonetheless, their comments are appreciated, although they do not substantively alter the results of our review.


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References

Dart, RA, Gollub, S, Lazar, J, et al (2003) Treatment of systemic hypertension in patients with pulmonary disease: COPD and asthma.Chest123,222-243. [CrossRef] [PubMed]
 
Bristow, MR Beta-adrenergic receptor blockade in chronic heart failure.Circulation2000;101,558-569. [CrossRef] [PubMed]
 
Broeders, MA, Doevendans, PA, Bekkers, BC, et al Nebivolol: a third generation beta-blocker that augments vascular nitric oxide release; endothelial beta (2)-adrenergic receptor- mediated nitric oxide production.Circulation2000;102,677-684. [CrossRef] [PubMed]
 
Van de Water, A, Janssens, W, Van Nueten, J, et al Pharmacological and hemodynamic profile of nebivolol, a chemically novel, potent, and selective beta 1-adrenergic antagonist.J Cardiovasc Pharmacol1988;11,552-563. [CrossRef] [PubMed]
 
Varani, K, Manfredini, R, Iannotta, V, et al Effects of doxazosin and propranolol on A2A adenosine receptors in essential hypertension.Hypertension2002;40,909-913. [CrossRef] [PubMed]
 
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