Macrophage migration inhibitory factor in the nucleus of solitary tract decreases blood pressure in SHRs
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2013-01-01
Autores
Freiria-Oliveira, André Henrique [UNESP]
Blanch, Graziela Torres [UNESP]
Li, Hongwei
Colombari, Eduardo [UNESP]
Colombari, Débora Simões Almeida [UNESP]
Sumners, Colin
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Aims The macrophage migration inhibitory factor (MIF) is an intracellular inhibitor of the central nervous system actions of angiotensin II on blood pressure. Considering that angiotensin II actions at the nucleus of the solitary tract are important for the maintenance of hypertension in spontaneously hypertensive rats (SHRs), we tested if increased MIF expression in the nucleus of the solitary tract of SHR alters the baseline high blood pressure in these rats.Methods and resultsEight-week-old SHRs or normotensive rats were microinjected with the vector AAV2-CBA-MIF into the nucleus of the solitary tract, resulting in MIF expression predominantly in neurons. Rats also underwent recordings of the mean arterial blood pressure (MAP) and heart rate (via telemetry devices implanted in the abdominal aorta), cardiac- and baroreflex function. Injections of AAV2-CBA-MIF into the nucleus of the solitary tract of SHRs produced significant decreases in the MAP, ranging from 10 to 20 mmHg, compared with age-matched SHRs that had received identical microinjections of the control vector AAV2-CBA-eGFP. This lowered MAP in SHRs was maintained through the end of the experiment at 31 days, and was associated with an improvement in baroreflex function to values observed in normotensive rats. In contrast to SHRs, similar increased MIF expression in the nucleus of the solitary tract of normotensive rats produced no changes in baseline MAP and baroreflex function.ConclusionThese results indicate that an increased expression of MIF within the nucleus of the solitary tract neurons of SHRs lowers blood pressure and restores baroreflex function. © 2012 Published on behalf of the European Society of Cardiology. All rights reserved.
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Blood pressure, Gene transfer, Glutamate, Macrophage migration inhibitory factor, Nucleus of the solitary tract, Reactive oxygen species, enhanced green fluorescent protein, macrophage migration inhibition factor, messenger RNA, parvovirus vector, abdominal aorta, animal experiment, animal model, animal tissue, antihypertensive activity, blood pressure regulation, controlled study, heart hypertrophy, heart left ventricle pressure, heart rate, hypertension, immunohistochemistry, in vivo gene transfer, male, mean arterial pressure, microinjection, nerve cell, nonhuman, pressoreceptor reflex, priority journal, protein expression, rat, reverse transcription polymerase chain reaction, solitary tract nucleus, telemetry, viral gene delivery system, viral gene therapy, Animals, Arterial Pressure, Baroreflex, Cardiomegaly, Dependovirus, Disease Models, Animal, Genetic Therapy, Genetic Vectors, Heart Rate, Hypertension, Intramolecular Oxidoreductases, Macrophage Migration-Inhibitory Factors, Male, Microinjections, Rats, Rats, Inbred SHR, Rats, Inbred WKY, RNA, Messenger, Solitary Nucleus, Telemetry, Time Factors, Ventricular Function, Left
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Cardiovascular Research, v. 97, n. 1, p. 153-160, 2013.