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Dissociation of estrogen (E2) effects on the vasculature of diabetic rats
Author(s) -
Mitchell Adam,
Rogers Jennifer,
Myers Adam,
Mulroney Susan
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1148.6
Subject(s) - vasoprotective , medicine , endocrinology , myograph , diabetes mellitus , estrogen , vasodilation , kidney , nitric oxide
Decreases in circulating estrogen seen in human female diabetics may exacerbate vascular impairment seen in the hyperglycemic state alone. E2s role as a vasoprotective agent is not clear. In normal animals, we and others have shown that E2 increases NO production while decreases sensitivity to the vasodilator ACh and increases sensitivity to the vasoconstrictor PE. To examine whether there is dysregulation of E2 affect in the diabetic (D) vasculature, diabetes was induced by STZ injection in adult female rats concurrent with ovariectomy (OVX) and E2 replacement. After 8 weeks, mesenteric arteriolar reactivity to ACh and PE was measured on a wire myograph. STZ decreases ACh sensitivity (p<0.01) vs non‐diabetic (ND) vessels. While OVX reverses this effect (p=0.04), E2 replacement was same as OVX . Similarly, while STZ increases PE reactivity (p=0.02), and OVX reverses the effect (p=0.03), E2 replacement alone was not different than OVX . In the same animals, E2 replacement prevented the STZ‐induced increases in both GSI (~30%) and TIFI (~20%), indicating E2 efficacy in the D kidney. These data confirm the vascular effects of OVX in ND rats (reported by our lab), and extend the findings by showing that the effect of E2 replacement in the D female is lost in the resistance vessels, but not kidney. This dissociation in early diabetes may predispose the female to development of diabetic vascular complications.