ALPHA ADRENERGIC REGULATION OF AIRWAY BLOOD FLOW

Project: Research project

Project Details

Description

DESCRIPTION (Adapted from the applicant's abstract): Asthma is considered
to be an inflammatory airway disease. The airway circulation is therefore
likely to participate in some of its manifestations including exercise
induced bronchoconstriction, airway wall edema and the clearance of locally
released spasmogens. However, in contrast to airway smooth muscle
responsiveness, information on the effect of inflammation on airway vascular
smooth muscle responsiveness is lacking. The airway vasculature is part of
the systemic circulation and norepinephrine (NE) is the principal
neurotransmitter for the local adrenergic regulation of airway blood flow.
In recent studies, the principal investigator has shown that asymptomatic
asthmatics have an exaggerated vasoconstrictor response in the airway to an
inhaled adrenergic agonist and that repeated antigen challenge potentiates
NE-induced contraction of small bronchial arterial rings in sensitized
rabbits. These observations indicated that inflammation causes
alpha-adrenergic hyperresponsiveness of the airway vasculature, possibly as
an adaptive mechanism to counteract inflammatory vasodilation. The present
proposal is based on the hypothesis that the inflammatory increase in
alpha-adrenergic vascular responsiveness is due to upregulated
alpha-adrenergic signaling in vascular smooth muscle or decreased
alpha-adrenergic generation of endothelial relaxing factors, or both. This
will be tested by 1) assessing the effects of short-term and long-term
inflammatory stimulation on alpha1 and alpha2-receptor expression and
adrenergic signal transduction in rabbit bronchial arterial smooth muscle
and in endothelium, 2) correlating these findings with NE-induced bronchial
arterial contraction and its endothelial modulation, 3) comparing
alpha-adrenergic responsiveness of airway blood flow between asthmatics and
normals, and 4) determining the effect of glucocorticosteroids on enhanced
alpha-adrenergic responsiveness. These experiments are expected to yield
new information on the regulation of the airway circulation in bronchial
asthma and possibly identify novel therapeutic approaches.
StatusFinished
Effective start/end date4/1/983/31/02

Funding

  • National Heart, Lung, and Blood Institute
  • National Heart, Lung, and Blood Institute: $218,727.00
  • National Heart, Lung, and Blood Institute

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