Sirna-Mediated Silencing Of The Diencephalic Thyrotropin-Releasing Hormone Precursor Gene Decreases The Arterial Blood Pressure In The Obese Agouti Mice.

LANDA MS; SCHUMAN ML,; BURGUEÑO A; ALVAREZ A; GARCIA SI; PIROLA CJ

Frontiers in Biosciences

Albertson,

Lugar: New York; Año: 2007 vol. 12 p. 3431 - 3435

1093-9946

Obesity is associated with increased cardiovascular morbidity and mortality, in part through development of hypertension. Leptin promotes weight loss by reducing food intake and increasing energy expenditure through sympathetic stimulation. It also counteracts the starvation-induced suppression of thyroid hormone by up-regulating the expression of TRH. On the other hand, it is known that the extrahypothalamic TRH system participates in cardiovascular function modulating sympathetic system activity. In order to challenge the testable hypothesis that obesity may raise ABP through TRH system activation, we herein analyze the participation of the TRH system in the elevation of the ABP of the obese agouti yellow mice. These mice are characterized by they resistance to the weight reducing effect of leptin although they show a preserved sympathetic response to leptin along with a mild hypertension compared with the control strain (121±2 vs 102±2 mmHg, p<0.001, n=10). We report here that hyperleptinemic agouti mice showed 1.8-fold elevated diencephalic TRH content compared with control, and we demonstrate that a long lasting specific inhibition of TRH system by icv treatment with siRNA against preTRH normalizes SABP independently of the thyroid status. These results suggest that the interaction leptin?diencephalic TRH may be one of the mechanisms involved in the mild hypertension of the obese agouti mice.