Chronic estrogen depletion alters adenosine diphosphate-induced pial arteriolar dilation in female rats

We examined pial arteriolar reactivity to a partially endothelial nitric ox ide synthase (eNOS)-dependent vasodilator ADP as a function of chronic estr ogen status. The eNOS-dependent portion of the ADP response was ascertained by comparing ADP-induced pial arteriolar dilations before and after suffus ion of a NOS inhibitor, N-omega-nitro-L-arginine (L-NNA; 1 mM) in intact, o variectomized (Ovx), and 17 beta -estradiol (E-2) treated Ovx females. We a lso examined whether ovariectomy altered the participation of other factors in the ADP response. Those factors were the following: 1) the prostanoid i ndomethacin (Indo); 2) the Ca2+-dependent K+ (K-Ca) channel, iberiotoxin (I bTX); 3) the ATP-regulated K+ (K-ATP) channel glibenclamide (Glib); 4) the K-Ca-regulating epoxygenase pathway miconazole (Mic); and 5) the adenosine receptor 8-sulfophenyltheophylline (8-SPT). In intact females, the eNOS-dep endent (L-NNA sensitive) portion of the ADP response represented similar to 50% of the total. The ADP response was retained in the Ovx rats but L-NNA sensitivity disappeared. On E2 replacement, the initial pattern was restore d. ADP reactivity was unaffected by Indo, Glib, Mic, and 8-SPT. IbTX was as sociated with 50-80% reductions in the response to ADP in the intact group that was nonadditive with L-NNA, and 60-100% reductions in the Ovx group. T he present findings suggest that estrogen influences the mechanisms respons ible for ADP-induced vasodilation. The continued sensitivity to IbTX in Ovx rats, despite the loss of a NO contribution, is suggestive of a conversion to a hyperpolarizing factor dependency in the absence of E-2.