Doxazosin

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, nehivolol, and doxazosin into a class of [beta]-blockers with additional [alpha]-receptor-blocking action. It is known that labetalol, celiprolol, carvedilol, and nebivolol are [beta]-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 [beta]-blockers) produce vasodilatation by their [alpha]receptor-blocking effect. Labetalol has a higher affinity for [[alpha].sub.1] receptors than for [[beta].sub.1] and [[beta].sub.2] receptors, whereas carvedilol has twofold to threefold selectivity for [[beta].sub.1] receptors vs [[alpha].sub.1] receptors. (2) Nebivolol is a racemic mixture of d-enantiomers and l-enantiomers, and d-nebivolol is a highly selective [[beta].sub.1]-adrenergic receptor antagonist. In addition, nebivolol also produces direct vasorelaxation in humans and animals by endothelial [[beta].sub.2]-adrenergic receptor ligation with subsequent endothelial nitric oxide (NO) synthase-dependent NO production. (3,4) This effect can be abolished by inhibitors of NO synthase. (3)

Studies about doxazosin show that it selectively blocks the postjunctional [[alpha].sub.1]-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 [[alpha].sub.1]-adrenoceptor responses to various stimuli). (5) Some of the pharmacologic properties of doxazosin cannot be fully explained by its [alpha]-blocking effect, and a direct effect on adenosine receptors cannot be excluded. (5)

Suranjan Mukherjee

Royal Victoria Infirmary

Newcastle-upon-Tyne, UK

Saumitra Baksi

Monklands Hospital

Glasgow, UK

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

REFERENCES

(1) Dart RA, Gollub S, Lazar J, et al. Treatment of systemic hypertension in patients with pulmonary disease: COPD and asthma. Chest 2003; 123:222-243

(2) Bristow MR. Beta-adrenergic receptor blockade in chromic heart failure. Circulation 2000; 101:558-569

(3) 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. Circulation 2000: 102: 677-684

(4) 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 Cardiovase Pharmacol 1988; 11:552-563

(5) Varani K, Manfredini R, Iannotta V, et al. Effects of doxazosin and propranolol on A2A adenosine receptors in essential hypertension. Hypertension 2002; 40:909-913

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 or our review.

Richard A. Dart, MD, FCCP

Steve Gollub, MD, FCCP

Jason Lazar, MD, FCCP

Chandra Nair, MD, FCCP

David Schroeder, MD

Steven H. Woolf, MD

Marshfield Clinic

Marshfield, WI

Correspondence to: Richard A. Dart. MD, FCCP. Department of Nephralogy and Hypertension, Marshfield Clinic, 1000 North Oaks Ave. Marshfield, WI 54449-5777; e-mail dart.richard@ marshfieldclinic.org

COPYRIGHT 2003 American College of Chest Physicians
COPYRIGHT 2003 Gale Group