Effect of Inhaled Racemic and (R)-Albuterol on Airway Vascular Smooth Muscle Tone in Healthy and Asthmatic Subjects

Abstract

Although the relative effect of racemic and (R)-albuterol on airway smooth muscle tone have been investigated in patients with airflow obstruction, the comparative effectiveness of these drugs in relaxing airway vascular smooth muscle is unknown. Therefore, we determined the actions of inhaled racemic and (R)-albuterol on airway mucosal blood flow (Qaw) normalized for anatomic dead space as an index of airway vascular smooth muscle tone in 11 healthy subjects and 10 subjects with mild asthma. We also monitored the forced expiratory volume in 1 second (FEV1) as an index of airway smooth muscle tone. Mean +/- SE baseline Qaw was 43.1 +/- 1.5 microl x min(-1) x ml(-1) in healthy subjects and 53.4 +/- 2.1 microl x min(-1) x ml(-1) in asthmatic subjects (p < 0.01). The corresponding values for FEV1 were 95.6 +/- 1.4 and 86.8 +/- 2.5% respectively, of predicted (p = 0.01). Racemic and (R)-albuterol caused a transient, dose-dependent increase of Qaw in healthy, but not in asthmatic subjects; the responses were not different between the two drugs. The FEV1 tended to increase more in asthmatics than in healthy subjects, again without a difference between the two drugs. These results show that racemic and (R)-albuterol have comparable effects on airway vascular smooth muscle and suggest that the blunted airway vascular smooth muscle response to albuterol in asthmatics is not related to (S)-albuterol.

Rapid corticosteroid effect on β2-adrenergic airway and airway vascular reactivity in patients with mild asthma

“…[21][22][23] The study also showed that albuterol responsiveness is blunted in asthmatic patients, which is again in keeping with similar previous findings. 22 The increase and abnormal adrenergic responsiveness of Q aw have been related to airway inflammation, supported by the finding that long-term treatment with an inhaled glucocorticoid or with an oral leukotriene modifier can reduce Q aw values and that long-term glucocorticoid administration can restore albuterol responsiveness in these patients.…”

Inhaled corticosteroids: effects on the airway vasculature in bronchial asthma

“…Whereas the b 2 -adrenoreceptor-mediated airway vasodilation is blunted in corticosteroid-naive asthmatics [94,106], the vasodilator effect of inhaled albuterol was present in asthmatic patients on inhaled corticosteroid therapy [5].…”

“…Although b 2 -adrenergic agonists cause vasodilation in the bronchial circulation predominantly through increased synthesis of endothelial NO [104,105], recent studies disclosed blunted b 2 -adrenoreceptor-mediated airway vasodilation in asthmatics [94,106]. In addition to impaired signal transduction or decreased expression of b-adrenergic receptors [102], the attenuation of the b 2 -adrenergic agonist-induced vasodilation might be due to maximal vasodilation reached in response to airway inflammation [5].…”

Inhaled Levosalbutamol Versus Inhaled Salbutamol in Acute Exacerbation of Asthma

“…Different clinical studies especially in children have shown that levosalbutamol has a similar bronchodilator ability as racemic salbutamol even if given at one-half or one-fourth the dose. [6][7][8][9][10][11] It is shown in different studies that salbutamol given by nebulizer or pressurised metered dose inhaler with spacer produces same effect. 12…”