The action of prazosin and propylene glycol on methoxamine‐induced bronchoconstriction in asthmatic subjects.

Abstract

The effect of 1 mg inhaled prazosin on bronchoconstriction induced by methoxamine was investigated in seven asthmatic subjects. Prazosin caused significant inhibition of the methoxamine‐induced bronchoconstriction in six of the seven patients. These findings suggest that methoxamine produces bronchoconstriction in asthmatic subjects via stimulation of alpha‐adrenoceptors. In previous studies propylene glycol has been used as a vehicle for delivery of prazosin. This substance was found to cause significant inhibition of methoxamine effects and to shift the dose response curve to histamine to the right in four of seven patients.

Adrenergic airway vascular smooth muscle responsiveness in healthy and asthmatic subjects

“…␣ 1 -Adrenergic responsiveness. Our study showed airway vascular hyperresponsiveness to methoxamine in asthmatic subjects, similar to the previously demonstrated airway hyperresponsiveness to ␣-adrenergic agonists (7,23). The mechanisms responsible for the asthma-associated smooth muscle hyperresponsiveness are not known.…”

“…There appear to be differences in the adrenergic responsiveness of airway smooth muscle between healthy and asthmatic subjects. For example, several investigators have reported that inhaled ␣ 1 -adrenergic agonists cause airflow obstruction in patients with asthma but not in healthy subjects (7,23). Conversely, ␤ 2 -adrenergic agonist-induced bronchodilation may be blunted in some patients with asthma, although the clinical significance of this defect has been called into question (4,6,16,24,25).…”

Inhibition of methoxamine‐induced bronchoconstriction by ipratropium bromide and disodium cromoglycate in asthmatic subjects.

“…All subjects visited the laboratory on two to three occasions at the same time of day within a 2 week period. On the first occasion a methoxamine challenge was carried out as has been previously described (Black et al, 1982(Black et al, , 1984 following placebo pretreatment of 0.9% w/v saline. Briefly, resting forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) were measured using a dry vitalograph spirometer and following this, 2 ml of 0.9% w/v saline were administered over approximately 10 min using a Hudson's nebulizer with a flow rate of 6-7 /min.…”

“…All subjects visited the laboratory on two to three occasions at the same time of day within a 2 week period. On the first occasion a methoxamine challenge was carried out as has been previously described (Black et al, 1982(Black et al, , 1984 been recorded, the methoxamine challenge was commenced. On the third day 2 ml of DSCG (20 mg) was administered via a Hudson's nebulizer before the methoxamine challenge.…”

“…Prazosin an a-adrenoceptor agonist, produces broncho-significantly antagonized the effects of methoconstriction in asthmatic subjects (Black et xamine, providing evidence that the responses al., 1982). Since there have been reports of were in fact mediated via a-adrenoceptors methoxamine possessing R-adrenoceptor (Black et al, 1984). antagonist properties (Karim, 1965) it was possIt is still not known however, where these aible that methoxamine-induced bronchocon-adrenoceptors are situated.…”