Alterations in EDHF-mediated hyperpolarization and relaxation in mesenteric arteries of female rats in long-term deficiency of oestrogen and during oestrus cycle

1 This study was undertaken to determine whether endothelium-dependent relaxations are altered in mesenteric arteries from young female rats during oestrus cycle and after castration. 2 The contractile response to phenylephrine (Phe) was significantly enhanced in arteries from rats subjected to ovariectomy than in those from sham-operated (control) rats. Treatment of ovariectomized rats with 17 beta -oestradiol returned the Phe response to the control level. Arteries from rats at the diestrus stage also exhibited greater contraction in response to Phe. In the presence of 100 muM N-G-nitro-L-arginine (L-NOARG), the enhancement of the Phe contractile response associated with oestrogen deficiency was not observed. 3 Endothelium-dependent relaxations elicited by acetylcholine (ACh) in arteries precontracted with Phe were significantly reduced in ovariectomized and diestrus rats regardless of whether endothelium-derived nitric oxide (NO) was blocked with L-NOARG. Treatment with 17 beta -oestradiol prevented the reduced vascular relaxant response to ACh in ovariectomized rats. The reduction in the ACh responses observed in ovariectomized and diestrus rats was eliminated when 500 nM apamin and 100 nM charybdotoxin were present. 4 ACh-induced endothelium-dependent hyperpolarizations were depressed in arteries from ovariectomized and diestrus rats. The hyperpolarizing response to ACh was significantly improved when ovariectomized rats were treated with 17 beta -oestradiol. The resting membrane potentials and pinacidil-induced hyperpolarizations were unaffected by ovariectomy or the diestrus stage. 5 These results suggest that oestrogen-deficient states of both short and long duration reduce the basal release of NO from the endothelium and specifically attenuate endo thelium-dependent hyperpolarization and relaxation transduced by endothelium-derived hyperpolarizing factor.