AORTIC WALL SUBSTANCE P AND PERMEABILITY

Project: Research project

Description

The long-term objective of this line of study is to elucidate the
role(s) of neuropeptide tachykinins in vascular wall physiology,
beginning with substance P (SP). The specific aim of this
application is based upon preliminary studies and will test the
WORKING HYPOTHESIS that endogenous SP can enhance aortic transmural
permeability to circulating plasma albumin. Since the nourishment
and will-being of any vessel wall (and in turn the tissue served
by the vessel) is dependent upon transmural permeability, it is
absolutely critical to identify and characterize endogenous
substances which influence vascular wall permeability. To date SP
is postulated to serve in nociceptive neural transmission and has
pronounced effects upon the permeability of the microcirculation
of inflammed tissue sites. However, there have been no studies of
SP's effects upon physiology of the macrocirculation, e.g., the
aorta, under normal or abnormal states. The studies outlined in
this proposal will examine in vivo aortic albumin permeablility
after manipulations designed to both trigger or inhibit SP
interaction with the aorta. The working hypothesis will be tested with three series of in vivo
electrical field stimulation experiments: 1) in the absence of any
SP antagonism, 2) with the SP-antagonist spantide bathing the aorta
before and during field stimulation, and 3) after pretreatment with
capsaicin, an agent which causes prolonged depletion of SP-
containing nerves. Each experimental protocol will be accompanied
by in vitro determinations of aortic SP content and plasma albumin
flux by use of radioimmunoassay and fluorometric tracer techniques,
respectively. These procedures will be performed to obtain
evidence for changes of both the endogenous SP pool and albumin
flux in the aorta. If the results support the hypothesis this would demonstrate that
endogenous SP can alter aortic permeability. If true, this would
be the first evidence that an endogenous, neurally-sequestered
peptide (reported to prompt inflammatory events) can exert
alterations upon permeability of the macrocirculation. The
implications of this finding for control of normal aortic
permeability, as well as mechanisms of vascular inflammatory injury
per atherosclerosis or hypertensive vessel disease, would be novel
as well as significant.
StatusFinished
Effective start/end date4/1/893/31/93

Funding

  • National Institutes of Health

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Substance P
Permeability
Blood Vessels
Aorta
Tachykinins
Capillary Permeability
Neuropeptides
Serum Albumin
Synaptic Transmission
Radioimmunoassay
Albumins
Atherosclerosis