Thyrotropin-releasing hormone (TRH) plays an important role in central 
cardiovascular regulation through the activation of different neurotransmitter 
systems at distinct extrahypothalamic sites. To study possible alterations in 
the TRH system in the hypertensive state, we measured TRH concentration in 
cerebrospinal fluid and TRH content of the preoptic area in spontaneously 
hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) by radioimmunoassay. In 
addition, we also measured the density of the TRH receptor in this area by a 
rapid filtration technique using [3H]methyl-TRH. We found a significant increase 
in both the TRH content (634 +/- 61 versus 350 +/- 26 pg/mg protein, SHR versus 
WKY; P < .01, n = 5) and density of TRH receptors without changes in affinity 
(Bmax, 5.0 +/- 0.1 versus 3.3 +/- 0.1 fmol/mg protein, P < .01, n = 4). An 
increase in TRH concentration was also found in the cerebrospinal fluid of SHR 
(30 +/- 3 versus 21 +/- 2 pg/mL, P < .01, n = 5), suggesting increased TRH 
release in the central nervous system. Northern blot analysis indicated a 
threefold augmented abundance of TRH precursor mRNA in the preoptic area of SHR. 
A polyclonal antibody raised against TRH injected peripherally or 
intracerebroventricularly lowered arterial blood pressure in SHR but not in WKY. 
In addition, long-term treatment with enalapril (5 mg/kg twice daily), which was 
effective in inhibiting serum angiotensin-converting enzyme activity by more 
than 50%, decreased arterial blood pressure and preoptic area TRH content of 
SHR, whereas another vasodilator, diltiazem (10 mg/kg every 8 hours), failed to 
produce a similar change.(ABSTRACT TRUNCATED AT 250 WORDS)