Acute and long-term effects of 17 beta-oestradiol on agonist-stimulated force in rat tail artery

The effects of 17 beta-oestradiol on the force responses to KCI and noradrenaline were investigated in rings of the rat tail artery. Incubation 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-synthase inhibitor L-NAME. Rings activated by an intermediate degree of depolarization (60 mM K+) were less affected by the steroid (58% of control force). The sustained force response to 1 mu M noradrenaline was reduced in the presence of 17 beta-oestiadiol to 60% of control value. Lower concentrations of 17 beta-oestradiol (0.1 and 1 mu M) were without acute effects on force development However. long-term effects of 17 beta-oestradiol on vessel reactivity were found at these low concentrations. Rings were cultured for 3-7 days in the absence or in the presence of the steroid before they were stimulated with agonists. Cultured rings developed an increased sensitivity to noradrenaline compared with freshly prepared ones. Cocaine (30 mu m) shifted the noradrenaline concentration-response curve to the left in freshly prepared rings while it had no effect in cultured ones. indicating that the increased sensitivity to noradrenaline in cultured rings depends on loss of noradrenaline uptake. Rings cultured for 7 days in the presence of 0.1 mu M 17 beta-oestradiol developed a more pronounced supersensitivity to noradrenaline (EC(50) for noradrenaline was 0.13+/-0.03 mu M in steroid exposed rings vs. 0.38+/-0.09 mu M in control rings). Thus, prolonged treatment with 17 beta-oestradiol results in a potentiation of noradrenaline evoked force. in contrast to the acute effect of the steroid.