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Communications to the Editor |

α1-Adrenoreceptors and Pulmonary Hypertension FREE TO VIEW

François Chabot, MD; Francine Schrijen, MD, FCCP; Claude Saunier, MD
Author and Funding Information

Affiliations: Universitaire de Nancy Vandoeuvre-les-Nancy, France,  University of Southampton Southampton, United Kingdom

Correspondence to: François Chabot, MD, Service des Maladies Respiratoires et Réanimation Respiratoire, CHU Nancy-Brabois, rue du Morvan, 54511 Vandoeuvre-les-Nancy, France



Chest. 2000;117(5):1523-1524. doi:10.1378/chest.117.5.1523
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To the Editor:

We read with interest the article by Salvi (June 1999),1 who suggests that α1-adrenoreceptors present in the pulmonary vasculature play an important role in regulating physiologic responses, such as hypoxic pulmonary vasoconstriction (HPV). Several studies have demonstrated thatα 1-blockers either abolish or attenuate HPV, whereas other studies have demonstrated no effect (see Salvi,1for review). Considering these conflicting results, we investigated the effects of urapidil, an α1-blocker, in vivo, on the pulmonary vascular tone.2

As HPV predominates in the small pulmonary arterioles, we studied not only the pulmonary vascular resistance but also the pressure/flow relationship in a peripheral portion of the lung during normoxia and hypoxia in anesthetized intact dogs.3 We used a double-lumen catheter wedged in a distal pulmonary artery, where pressure could be increased by hypoxia or pharmacologically modified without influencing the rest of the circulation.3In this preparation, most of the conduit arteries were excluded because HPV predominates in the small vessels and segmental differences in vasomotor reactivity have been well documented in the pulmonary vasculature.4

In nine anesthetized spontaneously breathing dogs, mixed venous blood was infused at known flows in 15 wedged areas (vascular volume about 0.7 mL) to study the pressure/flow relation and to compute the peripheral pulmonary vascular resistance (PPVR). The pressure/flow curves were determined during local infusion of isotonic glucose followed by increasing concentrations of urapidil (1 nmol/L, 0.1μ mol/L, and 10 μmol/L), mixed with the blood infusion. The dogs breathed alternately air or a hypoxic mixture (fraction of inspired oxygen, 10%; fraction of inspired carbon dioxide, 3%). During normoxia or acute normocapnic hypoxia, urapidil induced no change in PPVR. These results show that, in our preparation, at the concentrations studied, urapidil had no effect on the peripheral pulmonary vascular tone. Higher concentrations (1 mmol/L) would have led to systemic hypotension.

In conclusion, our results do not support the hypothesis thatα 1-adrenoreceptors present in the pulmonary vasculature play an important role in regulating HPV.

References

Salvi, SS (1999) α1-Adrenergic hypothesis for pulmonary hypertension.Chest115,1708-1719. [CrossRef] [PubMed]
 
Chabot, F, Schrijen, F, Saunier, C, et al Effect of urapidil on peripheral pulmonary vascular resistance in anesthetized dogs [abstract]. Am J Respir Crit Care Med. 1996;;153 ,.:A586
 
Schrijen, F, Saunier, C, Chabot, F Peripheral pulmonary vascular resistance.J Appl Physiol1993;74,613-616. [PubMed]
 
Kemp, BK, Smolich, JJ, Cocks, TM Evidence for specific regional patterns of responses to different vasoconstrictors and vasodilators in sheep isolated pulmonary arteries and veins.Br J Pharmacol1997;121,441-450. [CrossRef] [PubMed]
 
To the Editor:

I am grateful to Dr. Francois Chabot and colleagues for their kind letter, in which they suggest thatα 1-adrenoreceptors do not play an important role in mediating hypoxic pulmonary vasoconstriction. They have based this view on their previous work, in which they demonstrated that urapidil had no effect on peripheral pulmonary vascular resistance in anesthetized dogs exposed to hypoxia.

I would like to raise the following points in response to their comments:

1. Although the dogs were exposed to hypoxia, they do not mention the amount of decrease in peripheral pulmonary vascular resistance produced by hypoxia. Although this work was presented as an abstract at the American Thoracic Society Meeting in 1996, it has not been formally published since. The methodology and study design published in the abstract is inadequate to determine the validity of their work. It would have been useful if their work was published in a peer-reviewed journal.

2. A vast amount of literature has clearly shown convincing evidence for the role of α1-adrenergic receptors in mediating hypoxic vasoconstriction (reviewed in detail in my published hypothesis).1

3. Urapidil is clearly effective in lowering pulmonary artery pressure in patients with hypoxia-induced pulmonary hypertension.23

4. Unresponsiveness of dog peripheral pulmonary vascular resistance to urapidil does not in any way suggest no effect ofα 1-adrenoreceptors in mediating hypoxic pulmonary vasoconstriction. Urapidil is a specific α1-adrenergic antagonist. Indirect evidence from several published studies suggest that α1B adrenergic receptors are likely involved in mediating this response. Use of prazosin by Chabot et al, in their study, would have helped solve this issue. In addition, there is a wide interspecies variation in the pulmonary vascular response to hypoxia, as well as in the affinities of various drugs acting onα 1-adrenergic receptors.

References
Salvi, SS α1-Adrenergic hypothesis for pulmonary hypertension.Chest1999;115,1708-1719. [CrossRef] [PubMed]
 
Adnot, S, Andrivet, P, Piquet, J, et al The effects of urapidil therapy on hemodynamics and gas exchange in exercising patients with chronic obstructive pulmonary disease and pulmonary hypertension.Am Rev Respir Dis1988;137,1068-1074. [PubMed]
 
Spah, F, Kottman, R, Schmidt, U Effects of single intravenous administration of urapidil and diltiazem in patients with nonfixed pulmonary hypertension secondary to chronic obstructive lung disease.J Cardiovasc Pharmacol1994;23,517-524. [CrossRef] [PubMed]
 

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References

Salvi, SS (1999) α1-Adrenergic hypothesis for pulmonary hypertension.Chest115,1708-1719. [CrossRef] [PubMed]
 
Chabot, F, Schrijen, F, Saunier, C, et al Effect of urapidil on peripheral pulmonary vascular resistance in anesthetized dogs [abstract]. Am J Respir Crit Care Med. 1996;;153 ,.:A586
 
Schrijen, F, Saunier, C, Chabot, F Peripheral pulmonary vascular resistance.J Appl Physiol1993;74,613-616. [PubMed]
 
Kemp, BK, Smolich, JJ, Cocks, TM Evidence for specific regional patterns of responses to different vasoconstrictors and vasodilators in sheep isolated pulmonary arteries and veins.Br J Pharmacol1997;121,441-450. [CrossRef] [PubMed]
 
Salvi, SS α1-Adrenergic hypothesis for pulmonary hypertension.Chest1999;115,1708-1719. [CrossRef] [PubMed]
 
Adnot, S, Andrivet, P, Piquet, J, et al The effects of urapidil therapy on hemodynamics and gas exchange in exercising patients with chronic obstructive pulmonary disease and pulmonary hypertension.Am Rev Respir Dis1988;137,1068-1074. [PubMed]
 
Spah, F, Kottman, R, Schmidt, U Effects of single intravenous administration of urapidil and diltiazem in patients with nonfixed pulmonary hypertension secondary to chronic obstructive lung disease.J Cardiovasc Pharmacol1994;23,517-524. [CrossRef] [PubMed]
 
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