The universal response of a blood vessel to intimal injury is the deve
lopment of intimal hyperplasia, The etiology of this lesion is not ful
ly understood but is assumed to involve stimulation of receptors on sm
ooth muscle cells with their subsequent proliferation. Many receptor-m
ediated processes are coupled to G-proteins but little information exi
sts regarding the expression of G-proteins during the development of i
ntimal hyperplasia. This study examines the kinetics of G-protein expr
ession in experimental vein grafts. Male New Zealand White rabbits had
a right carotid interposition bypass graft using the ipsilateral exte
rnal jugular vein. These were harvested on days 1, 3, 5, 7, 14, and 28
postoperatively for histology (n = 3) for in vitro isometric tension
studies of potassium chloride, serotonin, bradykinin, and histamine (n
= 3), or for Western blot analysis (n = 3) of the G-protein subunits
(alpha(i1), alpha(i2), alpha(i3), alpha(s) and beta), The results show
that expression of alpha(i3) developed de novo, was detectable by day
1, and continued to increase through day 7, paralleling the developme
nt of intimal hyperplasia. The expression of alpha(s) (52 kDa) increas
ed significantly by day 1 and also continued to increase until day 7.
In contrast, expression for alpha(i2), alpha(s) (45 kDa) and beta subu
nits increased at a much slower rate from 1 to 7 days and remained con
stant thereafter. No alpha(i1) was detected. The contractile response
to potassium chloride was significantly reduced (36% of the response i
n the jugular vein) over the first 7 days and increased to 196% of the
jugular vein response at 14 and 28 days. There was minimal response t
o serotonin, bradykinin, and histamine over the first 7 days. Contract
ile responses to serotonin increased while those to bradykinin and his
tamine decreased from 7 to 28 days. This study demonstrates that there
are specific changes in alpha(i) and alpha(s) subunits within 24 hr o
f grafting and that increases in all G-proteins occur in a time depend
ent manner up to 7 days postoperatively. Microscopic development of in
timal hyperplasia occurs from days 3 to 5 and increases rapidly betwee
n 7 and 14 days. Changes in the expression of G-proteins in the vein g
rafts, particularly the alpha(i3) subunit, parallel this formation of
intimal hyperplasia. These alterations in G-protein expression do not
appear to correlate with G-protein-mediated, contractile responses in
the vein grafts. (C) 1996 Academic Press, Inc.