ACUTE AND LONG-TERM EFFECTS OF 17-BETA-ESTRADIOL ON AGONIST-STIMULATED FORCE IN RAT TAIL ARTERY

The effects of 17 beta-oestradiol on the force responses to KCI and no radrenaline were investigated in rings of the rat tail artery. Incubat ion with 10 mu M 17 beta-oestradiol for 100-295 min reduced the force amplitude after 5 min in high-K+ (140 mM) to 10% of the control value. The inhibitory effect of the steroid was unaffected by the NO-synthas e inhibitor L-NAME. Rings activated by an intermediate degree of depol arization (60 mM K+) were less affected by the steroid (58% of control force). The sustained force response to 1 mu M noradrenaline was redu ced in the presence of 17 beta-oestiadiol to 60% of control value. Low er concentrations of 17 beta-oestradiol (0.1 and 1 mu M) were without acute effects on force development However. long-term effects of 17 be ta-oestradiol on vessel reactivity were found at these low concentrati ons. Rings were cultured for 3-7 days in the absence or in the presenc e of the steroid before they were stimulated with agonists. Cultured r ings developed an increased sensitivity to noradrenaline compared with freshly prepared ones. Cocaine (30 mu m) shifted the noradrenaline co ncentration-response curve to the left in freshly prepared rings while it had no effect in cultured ones. indicating that the increased sens itivity to noradrenaline in cultured rings depends on loss of noradren aline uptake. Rings cultured for 7 days in the presence of 0.1 mu M 17 beta-oestradiol developed a more pronounced supersensitivity to norad renaline (EC(50) for noradrenaline was 0.13+/-0.03 mu M in steroid exp osed rings vs. 0.38+/-0.09 mu M in control rings). Thus, prolonged tre atment with 17 beta-oestradiol results in a potentiation of noradrenal ine evoked force. in contrast to the acute effect of the steroid.