Inosine-induced vasoconstriction is mediated by histamine and
thromboxane derived from mast cells.
Shepherd, Rebecca K., and Brian R. Duling.
Department of Molecular Physiology and Biological Physics, Box 449,
University of Virginia School of Medicine, Charlottesville, Virginia
22908
APStracts 2:0345H, 1995.
Mast cell degranulation has been shown to release products that cause
arteriolar constriction. We have previously reported that two
nucleosides, adenosine and inosine, cause vasoconstriction of
isolated hamster cheek pouch arterioles by stimulating degranulation
of periarteriolar mast cells. The objectives of the present study
were to characterize the nucleoside-dependent vasoconstriction in
vivo and to determine the mediator or mediators responsible. We
examined the vasomotor effect of inosine on arterioles in the cheek
pouches of anesthetized hamsters (70 mg/kg pentobarbital sodium) in
the control situation, and in the presence of receptor antagonists
for histamine (H1, "aH1"), thromboxane A2 ("aTX"),
and leukotrienes ("aLT"). Most experiments were carried out
using inosine applied once locally via micropipette to arterioles and
observing the subsequent response. Over a range of inosine
concentrations in the pipette from 10-5 to 10-3 M, we observed a
dose-dependent increase in both the incidence and magnitude of
constriction. In addition, mast cell staining with ruthenium red was
observed following stimulation with inosine, an indication of mast
cell degranulation. Neither the H1, TX, nor the LT antagonist alone
had a significant effect on the vasomotor response to inosine.
However, combined H1 and TX blockade significantly reduced both the
incidence and magnitude of inosine-induced constriction. These data
establish that inosine-induced constriction occurs in vivo and
support the role of mast cells in this response. Furthermore, they
suggest that multiple mediators, primarily histamine and thromboxane,
are responsible for the observed constriction.
Received 5 April 1995; accepted in final form 7 August 1995.
APS Manuscript Number H330-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 14 August 1995.