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- W60053415 abstract "Protection of vasculature endothelial cells (EC) by induction of heme oxygenase (HO) may account for its previously noted anti-hypertensive effects. HO degrades heme, a pro-oxidant, into bilirubin, an anti-oxidant, and CO an anti-apoptotic vasodilator. We explored the anti-hypertensive mechanism of HO in diabetic spontaneously hypertensive rats (SHR). We hypothesized that HO prevents hypertension, worsened by diabetes, through reduction of oxidative stress and inhibition of EC apoptosis which increases vascular contraction to phenylephrine. SHR and WKY (control) rats were treated with streptozotocin (STZ) to induce diabetes and SnCl2 to upregulate HO-1. SHR blood pressures were significantly elevated compared to WKY (P<0.05) and worsened by diabetes (P<0.05) while treatment with SnCl2 attenuated this increase (P<0.01). SnCl2 increased HO-1 protein and HO activity leading to decreased levels of COX-2 and 3-NT, markers of oxidative stress by 65% and 49% respectively. The reduction in oxidative stress resulted in increased expression of the anti-apoptotic proteins Akt and Bcl-2. The restoration of these anti-apoptotic proteins contributed to reduced circulating endothelial cells (CEC) in the peripheral blood (cells/mL), a maker of endothelial dysfunction (30 ± 5 in SHR vs. 7 ± 2 in WKY, P<0.005). Diabetic SHR demonstrated a greater increase in CEC (47 ± 5) compared with non-diabetic; Treatment with SnCl2 significantly reduced CEC in diabetic (17 ± 6, P<0.005 vs. untreated) and non-diabetic (7 ± 3, P<0.005 vs. untreated) SHR. Diabetes significantly increased contractility but this increase was attenuated by induction of HO activity. HO induction in diabetic rats restored non-diabetic levels of contractility in WKY and partially (71%) reduced contraction in SHR. These results suggest that pharmacological induction of HO-1 in diabetic hypertensive rats reduces oxidative stress, allows EC to maintain an anti-apoptotic environment through increased anti-apoptotic protein expression and restores endothelial responses to prevent hypertension." @default.
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- W60053415 date "2006-10-31" @default.
- W60053415 modified "2023-10-09" @default.
- W60053415 title "Abstract 168: Prevention of Endothelial Cell Dysfunction and Apoptosis Through the Induction of Heme Oxygenase-1 Normalizes Blood Pressure in Diabetic Spontaneously Hypertensive Rats" @default.
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