Thyrotropin-releasing hormone (TRH) plays an important role in central 
cardiovascular regulation. Recently, we described that the TRH precursor gene 
overexpression induces hypertension in the normal rat. In addition, we published 
that spontaneously hypertensive rats (SHR) have central extrahypothalamic TRH 
hyperactivity with increased TRH synthesis and release and an elevated TRH 
receptor number. In the present study, we report that intracerebroventricular 
antisense (AS) treatment with a phosphorothioate oligonucleotide against the TRH 
precursor gene significantly diminished up to 72 hours and in a dose-dependent 
manner the increased diencephalic TRH content, whereas normalized systolic blood 
pressure (SABP) was present in the SHR compared with Wistar-Kyoto (WKY) rats. 
Although basal thyrotropin was higher in SHR compared with WKY rats and this 
difference disappeared after antisense treatment, no differences were observed 
in plasma T4 or T3 between strains with or without AS treatment, indicating that 
the effect of the AS on SABP was independent of the thyroid status. Because the 
encephalic renin-angiotensin system seems to be crucial in the development 
and/or maintenance of hypertension in SHR, we investigated the effect of 
antisense inhibition of TRH on that system and found that TRH antisense 
treatment significantly diminished the elevated diencephalic angiotensin II (Ang 
II) content in the SHR without any effect in control animals, suggesting that 
the Ang II system is involved in the TRH cardiovascular effects. To summarize, 
the central TRH system seems to be involved in the etiopathogenesis of 
hypertension in this model of essential hypertension.