Heterozygous disruption of renal outer medullary potassium channel in rats is associated with reduced blood pressure
| Autor: | Xiaoyan Zhou, Kathleen A. Sullivan, Yonghua Zhu, Melba Hernandez, Zuo Zhang, James B. Wade, Denis Y. Streltsov, Daphne Szeto, Wanda Sharif-Rodriguez, Sarah Beth Horwitz, Paul A. Welling, Yan Cui, John Levorse, Gail Forrest, Bindhu Michael, Li Wang, Leslie Ann Balogh, Yi Pan, Maya Dajee, Olga Urosevic-Price, Myung K. Shin, Sophie Roy, Lei Zhu |
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| Rok vydání: | 2013 |
| Předmět: |
Male
medicine.medical_specialty Heterozygote Knockout rat Sodium-Potassium-Chloride Symporters Blood Pressure Bartter syndrome Kidney Article Internal medicine Internal Medicine medicine Loop of Henle Animals Potassium Channels Inwardly Rectifying Gene knockout Solute Carrier Family 12 Member 1 Rats Inbred Dahl Renal sodium reabsorption Chemistry medicine.disease Rats Endocrinology Blood pressure medicine.anatomical_structure Phenotype ROMK Female Cotransporter |
| Zdroj: | Hypertension (Dallas, Tex. : 1979). 62(2) |
| ISSN: | 1524-4563 |
| Popis: | The renal outer medullary potassium channel (ROMK, KCNJ1 ) mediates potassium recycling and facilitates sodium reabsorption through the Na + /K + /2Cl − cotransporter in the loop of Henle and potassium secretion at the cortical collecting duct. Human genetic studies indicate that ROMK homozygous loss-of-function mutations cause type II Bartter syndrome, featuring polyuria, renal salt wasting, and hypotension; humans heterozygous for ROMK mutations identified in the Framingham Heart Study have reduced blood pressure. ROMK null mice recapitulate many of the features of type II Bartter syndrome. We have generated an ROMK knockout rat model in Dahl salt-sensitive background by using zinc finger nuclease technology and investigated the effects of knocking out ROMK on systemic and renal hemodynamics and kidney histology in the Dahl salt-sensitive rats. The ROMK −/− pups recapitulated features identified in the ROMK null mice. The ROMK +/− rats, when challenged with a 4% salt diet, exhibited a reduced blood pressure compared with their ROMK +/+ littermates. More importantly, when challenged with an 8% salt diet, the Dahl salt-sensitive rats with 50% less ROMK expression showed increased protection from salt-induced blood pressure elevation and signs of protection from renal injury. Our findings in ROMK knockout Dahl salt-sensitive rats, together with the previous reports in humans and mice, underscore a critical role of ROMK in blood pressure regulation. |
| Databáze: | OpenAIRE |
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