Estrogen restores postischemic sensitivity to the thromboxane mimetic U46619 in rat pial artery.
The objectives of the study were to (1) characterize the dose-response relationship to the TXA2 analog, U46619 (0.01, 0.1, and 1 micromol/L) after global cerebral ischemia, (2) determine whether chronic 17beta-estradiol (E2) replacement alters this relationship, and (3) determine if E2's mechanisms are transduced through cognate estrogen receptors. Rats were assigned to five groups (n=6): placebo-implanted ovariectomized (OVX) females, OVX plus chronic E2 (CE), OVX plus acute E2 (AE), OVX plus chronic E2 plus the estrogen receptor inhibitor ICI 182,780 (CEI), and OVX plus acute E2 plus ICI 182,780 (AEI). Rats were anesthetized, intubated, cannulated (femoral artery and vein), fitted with a closed cranial window, and subjected to 15-min reversible forebrain ischemia (4-vessel occlusion, 4-VO) and 60 mins of reperfusion. Arterial blood gases, intrawindow pressure, and temperature were controlled. Vessel diameter was measured before and 5 mins after superfusion of each concentration of U46619. Compared with preischemic responses, contractile response to U46619 was depressed at all concentrations after ischemia in the OVX group. In the chronic E2 and acute E2 groups, contractile response to 1 micromol/L of U46619 was normalized to near baseline values. However, in the CEI and the AEI groups, postischemic vasoconstriction was similar to that observed in the OVX rats. We conclude that E2 targets the cerebral microvasculature to preserve postischemic pial artery reactivity and that the effect is receptor mediated. Restoration of normal constriction to vascular agonists may be an important mechanism by which E2 protects the vasculature and diminishes tissue damage after ischemia.
Qin
Xinyue
X
Johns Hopkins Medical Institutions, Baltimore, Maryland 21287, USA.
Hurn
Patricia D
PD
Littleton-Kearney
Marguerite T
MT
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D002536:Cerebral Arteries / Q000187:drug effects* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000097:blood / Q000494:pharmacology*; D005260:Female; D006454:Hemoglobins / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D002546:Ischemic Attack, Transient / Q000503:physiopathology*; D010052:Ovariectomy; D010100:Oxygen / Q000097:blood; D016548:Prosencephalon / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D011960:Receptors, Estrogen / Q000187:drug effects; D015427:Reperfusion Injury / Q000473:pathology; D013928:Thromboxane A2 / Q000494:pharmacology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D006454:Hemoglobins; D011960:Receptors, Estrogen; D014662:Vasoconstrictor Agents; D004958:Estradiol; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D010100:Oxygen