Journal article
Intracerebroventricular injection of adeno‐associated viral vector‐siRNA to silence mineralocorticoid receptors prevents aldosterone/salt‐induced hypertension and reduces its expression in the lamina terminalis
The FASEB journal, Vol.21(6), pp.LB120-LB120
2007
DOI: 10.1096/fasebj.21.6.LB120-c
Abstract
Chronic activation of brain mineralocorticoid receptors (MR) induces hypertension in animal models. We investigated the effect of intracerebroventricular injections of a recombinant adeno‐associated viral vector (AAV) carrying small interference (si) RNA to silence MR (AAV‐MR‐siRNA) on aldosterone/salt‐induced hypertension. A vector carrying scrambled siRNA (AAV‐SC‐siRNA) was administered as a control. Arterial blood pressure was measured continuously by telemetry for 21 days after AAV injections and DSI® transmitter implantation. AAV‐MR‐siRNA injection inhibited the development of aldosterone/salt‐induced hypertension (102.4±1.4 to 121.5±1.86 mmHg in SC‐siRNA, and 103.7±0.7 to 107.6±1.5 mmHg in MR‐siRNA). The efficacy of the AAV‐MR‐siRNA to reduce MR expression in the lamina terminalis was examined with immunohistochemistry. AAV‐MR‐siRNA injected rats showed a striking reduction in MR expression in the subfornical organ and organum vasculosum of the lamina terminalis in comparison to AAV‐SC‐siRNA rats. These results suggest that central MR play a role in the progression of aldosterone/salt‐induced hypertension. Central AAV‐MR‐siRNA administration constitutes an effective way to reduce the expression of MR in the brain and provides a useful method to investigate its pathophysiological role in aldosterone/salt‐induced hypertension. (NIH HL‐59676; HL‐62261; HL‐14388.)
Details
- Title: Subtitle
- Intracerebroventricular injection of adeno‐associated viral vector‐siRNA to silence mineralocorticoid receptors prevents aldosterone/salt‐induced hypertension and reduces its expression in the lamina terminalis
- Creators
- Daniel Badaue‐Passos - University of IowaBaojian Xue - University of IowaTerry Beltz - University of IowaRalph Johnson - University of IowaAlan Kim Johnson - Cardiovascular CenterMeredith Hay - University of Iowa
- Resource Type
- Journal article
- Publication Details
- The FASEB journal, Vol.21(6), pp.LB120-LB120
- Publisher
- The Federation of American Societies for Experimental Biology
- DOI
- 10.1096/fasebj.21.6.LB120-c
- ISSN
- 0892-6638
- eISSN
- 1530-6860
- Number of pages
- 1
- Language
- English
- Date published
- 2007
- Academic Unit
- Psychological and Brain Sciences; Neuroscience and Pharmacology; Health and Human Physiology; Neurology (Pediatrics)
- Record Identifier
- 9984213402202771
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