title: 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(omega)-nitro-L-arginine (L-NNA; 1 mM) in intact, ovariectomized (Ovx), and 17beta-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+ (K(Ca)) channel, iberiotoxin (IbTX); 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-dependent (L-NNA sensitive) portion of the ADP response represented approximately 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.
authors.affiliation: Neuroanesthesia Research Laboratory, University of Illinois at Chicago, Chicago, Illinois 60607, USA.
authors.forename: H L
authors.initials: HL
authors.lastname: Xu
authors.forename: R A
authors.initials: RA
authors.lastname: Santizo
authors.forename: H M
authors.initials: HM
authors.lastname: Koenig
authors.forename: D A
authors.initials: DA
authors.lastname: Pelligrino
mesh_terms: D000244:Adenosine Diphosphate / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology; D001160:Arterioles / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D002317:Cardiovascular Agents / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000378:metabolism; D004967:Estrogens / Q000172:deficiency*; D005260:Female; D005905:Glyburide / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D008825:Miconazole / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III; D019335:Nitroarginine / Q000494:pharmacology; D010052:Ovariectomy; D010455:Peptides / Q000494:pharmacology; D010841:Pia Mater / Q000098:blood supply*; D015221:Potassium Channels / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013806:Theophylline / Q000031:analogs & derivatives* / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
chemical_list: D000935:Antifungal Agents; D002317:Cardiovascular Agents; D004967:Estrogens; D007004:Hypoglycemic Agents; D010455:Peptides; D015221:Potassium Channels; D019335:Nitroarginine; D009569:Nitric Oxide; D000244:Adenosine Diphosphate; C064719:iberiotoxin; D008825:Miconazole; C031433:8-(4-sulfophenyl)theophylline; D000255:Adenosine Triphosphate; D013806:Theophylline; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D005905:Glyburide; D002118:Calcium; D007213:Indomethacin