Adrenergic airway vascular smooth muscle responsiveness in healthy and asthmatic subjects

Abstract

The purpose of the present study was to determine the responsiveness of airway vascular smooth muscle (AVSM) as assessed by airway mucosal blood flow (Qaw) to inhaled methoxamine (alpha(1)-agonist; 0.6-2.3 mg) and albuterol (beta(2)-agonist; 0.2-1.2 mg) in healthy [n = 11; forced expiratory volume in 1 s, 92 +/- 4 (SE) % of predicted] and asthmatic (n = 11, mean forced expiratory volume in 1 s, 81 +/- 5%) adults. Mean baseline values for Qaw were 43.8 +/- 0.7 and 54.3 +/- 0.8 microl. min(-1). ml(-1) of anatomic dead space in healthy and asthmatic subjects, respectively (P < 0.05). After methoxamine inhalation, the maximal mean change in Qaw was -13.5 +/- 1.0 microl. min(-1). ml(-1) in asthmatic and -7.1 +/- 2.1 microl. min(-1). ml(-1) in healthy subjects (P < 0.05). After albuterol, the mean maximal change in Qaw was 3.0 +/- 0.8 microl. min(-1). ml(-1) in asthmatic and 14.0 +/- 1.1 microl. min(-1). ml(-1) in healthy subjects (P < 0.05). These results demonstrate that the contractile response of AVSM to alpha(1)-adrenoceptor activation is enhanced and the dilator response of AVSM to beta(2)-adrenoceptor activation is blunted in asthmatic subjects.

Vasoconstriction after inhalation of budesonide: A study in the isolated and perfused rat lung

“…Furthermore, in the present study we have demonstrated that the perfusion flow rate in the IPL is sensitive to high concentrations of ICS and that the selective α 1 -adrenoceptor antagonist prazosin reduced the budesonide-induced vasoconstriction by about 50%, which suggest that the effect of budesonide is mediated through the α 1 -adrenoceptor [9,10]. Hence, in our model we hypothesise that the selective α 1 -adrenoceptor antagonist prazosin competes with NA at the binding sites of the α 1 -adrenoceptor within the lung vessels, and thus, renders the pressor effect induced by budesonide less pronounced.…”

“…This would indicate that noradrenergic signalling was involved in the corticosteroid sensitive regulation of smooth muscle tone in airway vasculature [9,10].…”

“…insight into the topic of vascular effects of ICS [4,[9][10] . They have demonstrated, in isolated human bronchial arterial smooth muscle cells [20], that corticosterone, budesonide and methylprednisolone dose-dependently inhibit -by an unknown but rapid mechanism -the extraneuronal uptake of NA.…”

Inhaled corticosteroids reduce asthma-associated airway hyperperfusion through genomic and nongenomic mechanisms

“…These findings have now been confirmed in human subjects using recently invented noninvasive methods for airway blood flow measurements [20][21][22][23]. By measuring the uptake of an inhaled, soluble inert gas (dimethyl-ether, DME) [24,25], mean airway mucosal blood flow values (comprising about 70% of total airway blood flow) were 24% to 77% higher in patients with stable asthma than in healthy controls [20,23]. Using acetylene rather than DME for 6 measurements, airway blood flow has been confirmed to be elevated in patients with mild persistent and moderate asthma compared with healthy subjects [26].…”

“…In anima l models of airway inflammation such as Ascaris suum sensitized sheep, antigen challenge has been shown to cause an increase in airway blood flow [18,19]. These findings have now been confirmed in human subjects using recently invented noninvasive methods for airway blood flow measurements [20][21][22][23]. By measuring the uptake of an inhaled, soluble inert gas (dimethyl-ether, DME) [24,25], mean airway mucosal blood flow values (comprising about 70% of total airway blood flow) were 24% to 77% higher in patients with stable asthma than in healthy controls [20,23].…”