| Autor: |
Song, Jin, Kost, Curtis K., Martin, Douglas S. |
| Předmět: |
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| Zdroj: |
Cardiovascular Research; Dec2006, Vol. 72 Issue 3, p456-463, 8p |
| Abstrakt: |
Abstract: Objectives: This study assessed whether the Rho kinase signaling pathway contributes to androgenic amplification of angiotensin II (Ang II) induced pressor and renal constrictor responses. Methods: Mean arterial pressure (MAP) responses to angiotensin II receptor 1 (AT1) inhibition were measured in conscious male New Zealand genetically hypertensive rats (NZGH) subjected to sham operation, castration or castration+testosterone replacement. MAP and renal vascular resistance (RVR) responses to Ang II were recorded with and without a Rho kinase inhibitor, fasudil, in anesthetized NZGH. Western blot was used to analyze target protein expression in the kidney. Results: MAP responses to AT1 receptor inhibition and exogenous Ang II were attenuated in castrated NZGH. The increase in RVR (mm Hg/ml/min/g kidney) at the maximum dose of Ang II was significantly lower in castrated NZGH than in sham operated NZGH. Testosterone replacement restored RVR responses to Ang II in castrated rats. Fasudil treatment reduced both MAP and RVR responses to Ang II in each group. In addition, the differential MAP and RVR responses to Ang II amongst the three groups were significantly attenuated by Rho kinase inhibition. Western blot showed that Rho kinase protein expression was reduced by castration, while testosterone replacement restored the Rho kinase protein levels in castrated rats. The phosphorylation of myosin phosphatase target subunit 1 (MYPT1), a downstream target of Rho kinase, was also increased by androgens. Conclusions: Collectively, these results indicate that androgens potentiate Ang II-induced renal vascular responses, an effect mediated at least partly via up-regulation of the Rho kinase signaling pathway. [Copyright &y& Elsevier] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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