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Macrophage migration inhibitory factor in hypothalamic paraventricular nucleus neurons decreases blood pressure in spontaneously hypertensive rats
Author(s) -
Li Hongwei,
Gao Yongxin,
Qi Yanfei,
Katovich Michael J.,
Jiang Nan,
Braseth Leah N.,
Scheuer Deborah A.,
Shi Peng,
Sumners Colin
Publication year - 2008
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/fj.08-108662
Subject(s) - medicine , endocrinology , angiotensin ii , immunostaining , muscle hypertrophy , blood pressure , renin–angiotensin system , inhibitory postsynaptic potential , macrophage migration inhibitory factor , downregulation and upregulation , chemistry , cytokine , immunohistochemistry , gene , biochemistry
Macrophage migration inhibitory factor (MIF) expression is increased by angiotensin II (Ang II) within paraventricular nucleus (PVN) neurons of nor‐motensive rats and acts via its intrinsic thiol protein oxidoreductase (TPOR) to counterregulate the central nervous system‐mediated pressor action of Ang II. Considering that the PVN‐mediated actions of Ang II are enhanced in spontaneously hypertensive rats (SHRs) and contribute to the development of hypertension in these animals, we investigated this MIF regulatory mechanism in SHRs. Here, we have demonstrated that Ang II failed to increase MIF protein expression in the PVN of SHRs. Furthermore, although basal levels of MIF protein and mRNA were similar in the PVN of SHRs and normotensive rats, immunostaining revealed that MIF was either absent from or diminished in PVN neurons of SHRs. AAV2‐mediated increases in MIF expression within PVN neurons of young (8 wk old) SHRs produced a chronic attenuation of hypertension and cardiac hypertrophy. However, similar AAV2‐mediated transduction of [C60S]‐MIF, which lacks TPOR activity, did not alter the development of hypertension or cardiac hypertrophy in SHRs. Collectively, these findings suggest that a lack of MIF expression within PVN neurons contributes to the development of hypertension and cardiac hypertrophy in SHRs.—Li, H., Gao, Y., Qi, Y., Katovich, M. J., Jiang, N., Braseth, L. N., Scheuer, D. A., Shi, P., Sumners, C. Macrophage migration inhibitory factor in hypothalamic paraventricular nucleus neurons decreases blood pressure in spontaneously hypertensive rats. FASEB J. 22, 3175–3185 (2008)