Further evidence for the selective disruption of intercellular communication by heptanol

The lack of selective gap junctional uncoupling agents has hampered evaluat ion of the contribution of intercellular communication to pharmacomechanica l coupling and vascular contractility. Thus we further explored the utility and selectivity of heptanol as a gap junctional uncoupling agent in isolat ed rat aortic rings. Fifty-two aortic rings were obtained from 15 rats and were precontracted to similar to 75% of maximum with phenylephrine (PE). Wh en contraction achieved steady state (similar to 5 min), a single concentra tion of heptanol (200 mu M) was added to each aortic ring at 1- to 3-min in tervals for up to 42 min post-PE addition. At early time points (5-10 min a fter PE), heptanol elicited an similar to 50% loss of tension (i.e., relaxa tion). At subsequent time points post-PE, a gradual and time-dependent decr ease in the magnitude of the heptanol-induced relaxation was observed until , after similar to 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 corr elation (P < 0.001, R = 0.81). Studies conducted on KCl-precontracted aorti c rings revealed no detectable heptanol-induced relaxation after developmen t of the steady-state KCl-induced contraction. These data extend our previo us observations to further document the potential utility of heptanol as a "relatively selective" uncoupling agent.