Thyrotropin-releasing hormone hyperactivity in the preoptic area of spontaneously hypertensive rats.
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)
D000704:Analysis of Variance; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D015152:Blotting, Northern; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004110:Diltiazem / Q000008:administration & dosage / Q000494:pharmacology; D004656:Enalapril / Q000008:administration & dosage / Q000494:pharmacology; D006973:Hypertension / Q000188:drug therapy / Q000209:etiology / Q000235:genetics / Q000503:physiopathology*; D008297:Male; D011301:Preoptic Area / Q000737:chemistry*; D012333:RNA, Messenger / Q000032:analysis; D011863:Radioimmunoassay; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D018025:Receptors, Thyrotropin-Releasing Hormone / Q000032:analysis / Q000235:genetics; D013973:Thyrotropin-Releasing Hormone / Q000032:analysis / Q000134:cerebrospinal fluid / Q000502:physiology*; D013997:Time Factors; D015854:Up-Regulation
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D012333:RNA, Messenger; D018025:Receptors, Thyrotropin-Releasing Hormone; D013973:Thyrotropin-Releasing Hormone; D004656:Enalapril; D004110:Diltiazem