Age‐ and estrogen‐dependent changes in cerebrovascular reactivity are mediated by constrictor prostanoids and superoxide

Abstract

The mechanisms underlying the conflicting effects of age and estrogen on cerebrovascular reactivity were examined in the middle cerebral artery (MCA) of mature multigravid (MA) female (F), older reproductively senescent (RS)‐F, and mature male (MM) rats. Ovary‐intact, ovariectomized (OvX) and OvX+estrogen‐replaced (OvX+ER) F were studied. Vasopressin (VP, 10−12–10−7M) reactivity was compared in pressurized MCAs pretreated with indomethacin (Indo, 10μM), NS398 (NS, 10μM), or SC560 (SC, 1μM). In MA‐F, Indo had no effect on VP response, whereas in MM, COX‐1(NS) or COX‐2 (SC) inhibition attenuated maximal reactivity by 25–26%. In contrast, in RS‐F, Indo reduced reactivity by 65%. The effects of oxidative stress on VP reactivity were examined in tempol (TPL, 1mM) treated MCA. In MA‐F, reactivity to VP was 20% lower in OvX+ER than in OvX. TPL reduced reactivity by 40% in OvX but had no effect in OvX+ER. Reactivity to VP in RS‐F was similar in OvX and OvX+ER. TPL attenuated reactivity by 30% in OvX+ER, but had no effect in OvX. These data suggest that: 1) constrictor prostanoids enhance vasoconstrictor responses to VP in MM and in older RS‐F but not in younger MA‐F; 2) estrogen reduces oxidative stress‐induced vasoconstriction in younger MA‐F, but enhances it in older RS‐F. (NIH: HL‐080402)