We recently showed that diencephalic TRH may mediate the central leptin-induced 
pressor effect. Here, to study the role of TRH in obesity-induced hypertension 
(OIH), we used a model of OIH produced by a high-fat diet (HFD, 45 days) in male 
Wistar rats. After 4 wk, body weight and systolic arterial blood pressure (SABP) 
increased in HFD animals. Plasma leptin was correlated with peritoneal adipose 
tissue. Then, we treated OIH animals with an antisense oligodeoxynucleotide and 
small interfering (si)RNA against the prepro-TRH. Antisense significantly 
decreased diencephalic TRH content and SABP at 24 and 48 h posttreatment. 
Similar effects were observed with siRNA against prepro-TRH but for up to 4 wk. 
Conversely, vehicle, an inverted antisense sequence and siRNA against green 
fluorescence protein, produced no changes. SABP decrease seems to be owing to an 
inhibition of the obesity-enhanced sympathetic outflow but not to an alteration 
in thyroid status. Using a simple OIH model we demonstrated, for the first time, 
that central TRH participates in the hypertension induced by body weight gain 
probably through its well-known action on sympathetic activity. Thus the 
TRH-leptin interaction may contribute to the strong association between 
hypertension and obesity.