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

Abstract

We examined pial arteriolar reactivity to a partially endothelial nitric oxide synthase (eNOS)-dependent vasodilator ADP as a function of chronic estrogen status. The eNOS-dependent portion of the ADP response was ascertained by comparing ADP-induced pial arteriolar dilations before and after suffusion of a NOS inhibitor, N ω-nitro-l-arginine (l-NNA; 1 mM) in intact, ovariectomized (Ovx), and 17β-estradiol (E2)-treated Ovx females. We also examined whether ovariectomy altered the participation of other factors in the ADP response. Those factors were the following: 1) the prostanoid indomethacin (Indo); 2) the Ca2+-dependent K+ (KCa) channel, iberiotoxin (IbTX); 3) the ATP-regulated K+(KATP) channel glibenclamide (Glib); 4) the KCa-regulating epoxygenase pathway miconazole (Mic); and 5) the adenosine receptor 8-sulfophenyltheophylline (8-SPT). In intact females, the eNOS-dependent (l-NNA sensitive) portion of the ADP response represented ∼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 restored. ADP reactivity was unaffected by Indo, Glib, Mic, and 8-SPT. IbTX was associated 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. The present findings suggest that estrogen influences the mechanisms responsible 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 E2.