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1 Laboratory of Molecular and
Integrative Urology,
The lack of selective gap junctional uncoupling
agents has hampered evaluation of the contribution of intercellular
communication to pharmacomechanical coupling and vascular
contractility. Thus we further explored the utility and selectivity of
heptanol as a gap junctional uncoupling agent in isolated rat aortic
rings. Fifty-two aortic rings were obtained from 15 rats and were
precontracted to ~75% of maximum with phenylephrine (PE). When
contraction achieved steady state (~5 min), a single concentration of
heptanol (200 µM) was added to each aortic ring at 1- to 3-min
intervals for up to 42 min post-PE addition. At early time points
(5-10 min after PE), heptanol elicited an ~50% loss of tension
(i.e., relaxation). At subsequent time points post-PE, a gradual and
time-dependent decrease in the magnitude of the heptanol-induced
relaxation was observed until, after ~40 min, addition of heptanol
was associated with little, if any, detectable relaxation. Linear
regression analysis of the magnitude of the heptanol-induced relaxation
vs. the square root of the elapsed time interval (from addition of PE)
revealed a highly significant negative correlation
(P < 0.001, R = 0.81). Studies conducted on
KCl-precontracted aortic rings revealed no detectable heptanol-induced
relaxation after development of the steady-state KCl-induced
contraction. These data extend our previous observations to further
document the potential utility of heptanol as a "relatively
selective" uncoupling agent.
vascular smooth muscle; rat aortic rings; phenylephrine; pharmacomechanical coupling
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