Abstract
Objective: The aims of this work were to determine if 1) ischemia alters pial artery responsiveness to the partially nitric oxide (NO)-dependent dilator, ADP, 2) the alteration depends on 17β-estradial (E2), and 3) NO contributes to E2 protective effects. Materials and Methods: Response to ADP and the non-NO-dependent dilator, PGE2, were examined through closed cranial windows. Ovariectomized (OVX) and E2-replaced (E25, 0.025 mg; or E50, 0.05 mg) rats were subjected to 15-minute forebrain ischemia and one-hour reperfusion. Endothelial NO synthase (eNOS) expression was determined in pre- and postischemic isolated cortical microvessels. Results: In OVX rats, ischemia depressed pial responses to ADP, but not to PGE2. Both doses of E2 maintained responses to ADP and had no effect on the response to PGE2. eNOS inhibition decreased the ADP response by 60% in the E25 rats and 50% in the E50 rats, but had no effect in the OVX rats. Compared to the OVX group, microvessel expression of eNOS was increased by E2, but postischemic eNOS was unchanged in both groups. Conclusions: The nearly complete loss of postischemic dilation to ADP suggests that normal non-NO-mediated dilatory mechanisms may be acutely impaired after ischemic injury. Estrogen's protective action on ADP dilation may involve both NO- and non-NO-mediated mechanisms.