THE EFFECT OF PASSIVE STRETCH ON THE RESPONSE OF THE FETAL RABBIT DUCTUS-ARTERIOSUS TO INDOMETHACIN, NORADRENALINE AND PROSTAGLANDIN E-2

The aim of this study was to determine the effect of varying stretch o f the ductus arteriosus on its contractile response to indomethacin an d noradrenaline, and its relaxant response to prostaglandin (PG) E-2. Isolated rings of ductus arteriosus obtained from fetal New Zealand Wh ite rabbits at 28 days gestation were mounted in vitro for measurement of isometric tension by a transducer connected to a vernier control. The responses of the ductus to drugs at varying degrees of passive str etch were corrected to a standard contraction in response to 65 mM pot assium at a standard level of stretch. Increasing stretch across the r ange 1.0-5.9 mN increased the contractile response to indomethacin and noradrenaline (the latter in the presence of 1 mu M indomethacin and 1 or 10 nM PGE(2)) in a virtually identical manner. The sensitivity of the vessel to noradrenaline in the presence and absence of indomethac in and its sensitivity to the relaxant effect of PGE(2) in the presenc e of indomethacin were unaffected by increasing stretch. The extent of contractile tone present which was not inhibited by endogenous PGE(2) increased with increasing stretch. It was concluded that: (1) the con tractile response to indomethacin can be profoundly altered by the deg ree of spontaneous tone in the vessel; (2) the magnitude of the contra ction induced by indomethacin is not a good index of the degree of inh ibition exerted by locally produced PGs in the vessel; and (3) locally produced PGs are likely to have a physiological role in maintaining p atency of the ductus arteriosus in utero.