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• W2078963353 abstract "ObjectiveUPBF is controlled in part by nitric oxide, which produces vasodilation by increasing cGMP. cGMP is hydrolyzed by phosphodiesterase (PDE), therefore, regulating vascular tone. We previously reported that PDE5 mRNA levels positively correlate with uterine blood flow in pregnant sheep. Our aim is to determine if reduced UPBF alters levels of PDE5 in the ovine placentome (maternal caruncle and fetal cotyledon).Study designReduction in UPBF was produced by a common internal iliac occluder. Placentomes were obtained and frozen at -80 degrees from either anesthetized animals (n = 2) with reduced UPBF (650 ± 50 ml/min (Normal = 900 ml/min) at either 48 or 72 hours after reduction) or matched control animals (n = 2). RNA was extracted and optimized real time PCR was utilized to assess PDE5 mRNA expression. PDE5 protein expression/localization was determined by Western Blot and immunohistochemistry.ResultsPDE5 mRNA levels were decreased in the caruncle of flow-restricted animals compared to controls (50% at 48 hrs). Cotyledons, however, showed increased PDE5 mRNA (2 fold at 48 hrs and 1.4 at 72 hrs). Western Blot analysis showed upregulation of PDE5 protein expression in the flow-restricted animals (Caruncle: 1.4 fold at 48 hrs and 1.7 at 72 hrs; Cotyledon 9.3 fold at 48 hrs and 12.4 at 72 hrs). PDE5 was not immunolocalized in any fetal stroma or vessels in either group. PDE5 staining was visualized in maternal stroma and vessels, however, the protein upregulation was not apparent by immunohistochemistry in the flow-restricted animals.ConclusionReduction in UPBF was associated with significant increases in PDE5 message and protein at 48 and 72 hours. We hypothesize that the increase in PDE5 suggests that an active feedback pathway exists to regulate cGMP levels and vasodilation in the ovine placentome. ObjectiveUPBF is controlled in part by nitric oxide, which produces vasodilation by increasing cGMP. cGMP is hydrolyzed by phosphodiesterase (PDE), therefore, regulating vascular tone. We previously reported that PDE5 mRNA levels positively correlate with uterine blood flow in pregnant sheep. Our aim is to determine if reduced UPBF alters levels of PDE5 in the ovine placentome (maternal caruncle and fetal cotyledon). UPBF is controlled in part by nitric oxide, which produces vasodilation by increasing cGMP. cGMP is hydrolyzed by phosphodiesterase (PDE), therefore, regulating vascular tone. We previously reported that PDE5 mRNA levels positively correlate with uterine blood flow in pregnant sheep. Our aim is to determine if reduced UPBF alters levels of PDE5 in the ovine placentome (maternal caruncle and fetal cotyledon). Study designReduction in UPBF was produced by a common internal iliac occluder. Placentomes were obtained and frozen at -80 degrees from either anesthetized animals (n = 2) with reduced UPBF (650 ± 50 ml/min (Normal = 900 ml/min) at either 48 or 72 hours after reduction) or matched control animals (n = 2). RNA was extracted and optimized real time PCR was utilized to assess PDE5 mRNA expression. PDE5 protein expression/localization was determined by Western Blot and immunohistochemistry. Reduction in UPBF was produced by a common internal iliac occluder. Placentomes were obtained and frozen at -80 degrees from either anesthetized animals (n = 2) with reduced UPBF (650 ± 50 ml/min (Normal = 900 ml/min) at either 48 or 72 hours after reduction) or matched control animals (n = 2). RNA was extracted and optimized real time PCR was utilized to assess PDE5 mRNA expression. PDE5 protein expression/localization was determined by Western Blot and immunohistochemistry. ResultsPDE5 mRNA levels were decreased in the caruncle of flow-restricted animals compared to controls (50% at 48 hrs). Cotyledons, however, showed increased PDE5 mRNA (2 fold at 48 hrs and 1.4 at 72 hrs). Western Blot analysis showed upregulation of PDE5 protein expression in the flow-restricted animals (Caruncle: 1.4 fold at 48 hrs and 1.7 at 72 hrs; Cotyledon 9.3 fold at 48 hrs and 12.4 at 72 hrs). PDE5 was not immunolocalized in any fetal stroma or vessels in either group. PDE5 staining was visualized in maternal stroma and vessels, however, the protein upregulation was not apparent by immunohistochemistry in the flow-restricted animals. PDE5 mRNA levels were decreased in the caruncle of flow-restricted animals compared to controls (50% at 48 hrs). Cotyledons, however, showed increased PDE5 mRNA (2 fold at 48 hrs and 1.4 at 72 hrs). Western Blot analysis showed upregulation of PDE5 protein expression in the flow-restricted animals (Caruncle: 1.4 fold at 48 hrs and 1.7 at 72 hrs; Cotyledon 9.3 fold at 48 hrs and 12.4 at 72 hrs). PDE5 was not immunolocalized in any fetal stroma or vessels in either group. PDE5 staining was visualized in maternal stroma and vessels, however, the protein upregulation was not apparent by immunohistochemistry in the flow-restricted animals. ConclusionReduction in UPBF was associated with significant increases in PDE5 message and protein at 48 and 72 hours. We hypothesize that the increase in PDE5 suggests that an active feedback pathway exists to regulate cGMP levels and vasodilation in the ovine placentome. Reduction in UPBF was associated with significant increases in PDE5 message and protein at 48 and 72 hours. We hypothesize that the increase in PDE5 suggests that an active feedback pathway exists to regulate cGMP levels and vasodilation in the ovine placentome." @default.
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• W2078963353 title "Increased expression of phosphodiesterase 5 (PDE5) in response to reduced uteroplacental blood flow (UPBF) in pregnant sheep" @default.
• W2078963353 doi "https://doi.org/10.1016/j.ajog.2004.10.373" @default.
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