Organic Anion Transporter 3 Contributes to the Regulation of Blood Pressure
| Autor: | Sanjay K. Nigam, Gregory Kaler, Wei Wu, Timo Rieg, Volker Vallon, Sushil K. Mahata, Gary Siuzdak, Satish A. Eraly, Sun-Young Ahn, William R. Wikoff, Bruce A. Barshop, Nitish R. Mahapatra, Jon A. Gangoiti, David M. Truong |
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| Rok vydání: | 2008 |
| Předmět: |
medicine.medical_specialty
Organic anion transporter 1 Xenopus Blood Pressure Endogeny Organic Anion Transporters Sodium-Independent Biology Excretion Mice chemistry.chemical_compound Adrenocorticotropic Hormone In vivo Corticosterone Internal medicine Renin Renin–angiotensin system medicine aldosterone organic anion transporter 3 thymidine corticosterone corticotropin organic anion transporter renin animal experiment blood level blood pressure regulation genetic polymorphism mouse nonhuman priority journal protein expression protein function sodium restriction animal blood blood pressure C57BL mouse drug antagonism metabolism mouse mutant oocyte Aldosterone Animals Mice Inbred C57BL Mice Knockout Oocytes General Medicine Metabolism Basic Research Endocrinology chemistry Nephrology biology.protein |
| Zdroj: | Journal of the American Society of Nephrology. 19:1732-1740 |
| ISSN: | 1046-6673 |
| DOI: | 10.1681/asn.2008020180 |
| Popis: | Renal organic anion transporters (OAT) are known to mediate the excretion of many drugs, but their function in normal physiology is not well understood. In this study, mice lacking organic anion transporter 3 (Oat3) had a 10 to 15% lower BP than wild-type mice, raising the possibility that Oat3 transports an endogenous regulator of BP. The aldosterone response to a low-salt diet was blunted in Oat3-null mice, but baseline aldosterone concentration was higher in these mice, suggesting that aldosterone dysregulation does not fully explain the lower BP in the basal state; therefore, both targeted and global metabolomic analyses of plasma and urine were performed, and several potential endogenous substrates of Oat3 were found to accumulate in the plasma of Oat3-null mice. One of these substrates, thymidine, was transported by Oat3 expressed in vitro. In vivo, thymidine, as well as two of the most potent Oat3 inhibitors that were characterized, reduced BP by 10 to 15%; therefore, Oat3 seems to regulate BP, and Oat3 inhibitors might be therapeutically useful antihypertensive agents. Moreover, polymorphisms in human OAT3 might contribute to the genetic variation in susceptibility to hypertension. Copyright � 2008 by the American Society of Nephrology. |
| Databáze: | OpenAIRE |
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