CHARACTERIZATION OF VASCULAR TONE ON LUNG FLUID BALANCE

Project: Research project

Description

The major objective of this research proposal is to test the
hypothesis that elevated pulmonary vascular tone and lung injury alter
the histaminergic, cholinergic, and adrenergic-mediated pulmonary
vascular responses such that both pulmonary capillary pressure and
microvascular permeability are affected, thereby disrupting lung fluid
balance. Specifically, this proposal will: 1) characterize different
models of elevated vascular tone with respect to the segmental
distribution of vascular resistance-compliance, and microvascular
permeability. The models of elevating vascular tone to be tested include
U46619 (thromboxane analog), endothelin-I (vasoconstrictor peptide),
norepinephrine, and angiotensin 11. 2) compare the responses to the
activation of the histaminergic, cholinergic, and adrenergic receptor
systems at normal vascular tone, and elevated vascular tone using the
models outlined above, and following lung injury using phorbol myristate
acetate (PMA) infusion, oleic acid infusion and HCL airway instillation.
3) compare the effect of active increases in vascular tone to passive
vessel distention when the receptor systems stated above are stimulated;
and 4) evaluate blood flow patterns that occur when the histaminergic,
cholinergic, and adrenergic receptor systems are activated in lungs with
normal vascular tone, elevated vascular tone, and injury. The segmental
distribution of pulmonary vascular resistance and compliance will be
determined by use of separate arterial, venous, and double vascular
occlusion techniques. Pulmonary microvascular permeability will be
evaluated by measurement of the capillary filtration coefficient,
isogravimetric capillary pressure, and the osmotic reflection
coefficient. In addition to physiological measurements, characterization
of the histaminergic, cholinergic, and adrenergic receptor systems will
be evaluated pharmacologically by kinetic rate-constant measurements and
biochemically by assaying for the presence of vasoactive mediators. The
effect of passive vessel distention on these receptor-mediated effects
will be assessed by perfusion with different hydrostatic pressures.
Finally, pulmonary blood flow patterns upon receptor stimulation will be
evaluated by observing the distribution of zinc cadmium sulfide compound
(a yellow fluorescing vascular marker) in control, vascular toned, and
injured lungs.
StatusFinished
Effective start/end date5/10/914/30/97

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $99,075.00
  • National Institutes of Health: $103,469.00
  • National Institutes of Health

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Water-Electrolyte Balance
Blood Vessels
Lung
Lung Injury
Vascular System Injuries
Cholinergic Receptors
Vascular Resistance
Adrenergic Agents
Adrenergic Receptors
Cholinergic Agents
Compliance
Cadmium Compounds
Hydrostatic Pressure
Thromboxanes
Endothelins
Osmotic Pressure
Angiotensins
Capillary Permeability
Vasoconstrictor Agents
Oleic Acid

ASJC

  • Medicine(all)