Oestradiol-induced relaxation of rabbit basilar artery by inhibition of voltage-dependent Ca channels through GTP-binding protein

1 Effects of oestradiol on the electrical and mechanical properties of the rabbit basilar artery were investigated by use of microelectrode, patch-clamp and isometric tension recording methods. 2 Oestradiol (10 nM-100 mu M) relaxed arterial tissue pre-contracted by excess [K](o) solution (30 mM) in a concentration-dependent manner. In Ca-free solution, histamine (10 mu M) and caffeine (20 mM) each produced a phasic contraction, but oestradiol (10 mu M) did not significantly affect their amplitude. 3 Oestradiol (less than or equal to 100 mu M) did not change the resting membrane potential of the artery whether in the presence or absence of TEA (10 mM). Action potentials observed in the presence of 10 mM TEA were abolished by oestradiol (100 mu M). 4 Oestradiol (1 mu M-100 mu M) inhibited the voltage-dependent Ba current in a concentration-dependent manner. Oestradiol (100 mu M) inhibited the Ba current observed in the presence of nicardipine (1 mu M) more than that in the absence of nicardipine (to 31.0% vs 62.0% of control). 5 GTP gamma S (30 mu M) in the pipette enhanced the inhibitory actions of oestradiol on the Ba current. On the other hand, with GDP beta S (1 mM) in the pipette, oestradiol failed to inhibit the Ba current. Pertussis toxin (PTX 3 mu g ml(-1)) in the pipette totally prevented the inhibitory action of oestradiol on the Ba current. 6 Oestradiol (less than or equal to 100 mu M) had no significant effect on the outward K currents evoked by a membrane depolarization. 7 These results strongly suggest that oestradiol relaxes arterial tissue by inhibition of voltage-dependent Ca channels and that it inhibits both nicardipine-sensitive and -resistant Ca currents via a PTX-sensitive GTP-binding protein. The main target of oestradiol among the arterial Ca channels seems to be the nicardipine-resistant Ca channel, rather than the nicardipine-sensitive one.