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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
Author(s) -
BadauePassos Daniel,
Xue Baojian,
Beltz Terry,
Johnson Ralph,
Johnson Alan Kim,
Hay Meredith
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.lb120-c
Subject(s) - lamina terminalis , mineralocorticoid receptor , aldosterone , medicine , small interfering rna , endocrinology , mineralocorticoid , subfornical organ , receptor , biology , angiotensin ii , central nervous system , cell culture , transfection , genetics
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.)