ESTROGEN INCREASES CGMP IN SELECTED BRAIN-REGIONS AND IN CEREBRAL MICROVESSELS

We have previously reported that exogenous and endogenous estrogen can amplify residual cerebral blood flow during experimental cerebral isc hemia. Because estrogen has been linked to nitric oxide and cyclic gua nosine monophosphate (cGMP) signaling in noncerebral tissue, we tested the hypothesis that long-term 17 beta-estradiol treatment increases b asal cGMP in brain homogenates and cerebral microvessels in female rab bits. We also determined whether there are important baseline gender-s pecific differences in regional cGMP. Adult female rabbits were implan ted with 17 beta-estradiol pellets, 10 mg (F10, n = 10) or 50 mg (F50, n = 13), and compared with untreated females (F, n = 19) and males wi th negligible estrogen (M, n = 19) (plasma 17 beta-estradiol levels of 4 +/- 4 pg/mL in M, 7 +/- 5 pg/mL in F, 141 +/- 74 pg/mL in F10, and 289 +/- 110 pg/mL in F50). Cyclic GMP was determined by radioimmunoass ay in cerebellum, hypothalamus, caudate nucleus, hippocampus, and cort ex. Cerebral microvessels were harvested from additional cohorts of un treated males and females or estradiol-implanted females (n = 6 per gr oup). Basal cGMP was higher in F versus M only in cerebellum. Estrogen -induced increases in regional cGMP were prominent in hippocampus at a ll doses (M = 43 +/- 26, F = 43 +/- 21, F10 = 84 +/- 24, F50 = 117 +/- 55 fmol/mg protein) and in cortex at the high dose (M = 78 +/- 55, F = 88 +/- 51, F10 = 69 +/- 34, F50 = 143 +/- 52 fmol/mg protein). Simil arly, microvascular cGMP increased only in females treated with the 50 mg dose (M = 77 +/- 13, F = 86 +/- 25, F10 = 106 +/- 35, F50 = 192 +/ - 88 fmol/mg protein). Therefore, 17 beta-estradiol increases cGMP con tent in parenchymal regions that are known physiologic targets for rep roductive steroids but are also areas of selective vulnerability to is chemic insult. Further, high doses of estrogenic steroids could amplif y cGMP signaling within the cerebral microvasculature.