RESUMO
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)
Assuntos
Hipertensão/fisiopatologia , Área Pré-Óptica/química , Hormônio Liberador de Tireotropina/fisiologia , Análise de Variância , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Animais , Anti-Hipertensivos/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Northern Blotting , Bloqueadores dos Canais de Cálcio/farmacologia , Diltiazem/administração & dosagem , Diltiazem/farmacologia , Enalapril/administração & dosagem , Enalapril/farmacologia , Hipertensão/tratamento farmacológico , Hipertensão/etiologia , Hipertensão/genética , Masculino , RNA Mensageiro/análise , Radioimunoensaio , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Receptores do Hormônio Liberador da Tireotropina/análise , Receptores do Hormônio Liberador da Tireotropina/genética , Hormônio Liberador de Tireotropina/análise , Hormônio Liberador de Tireotropina/líquido cefalorraquidiano , Fatores de Tempo , Regulação para CimaRESUMO
TRH increases the pressor response to acetylcholine through an increment in muscarinic receptors. As chronic atropinization produces a similar effect, we hypothesized that both phenomena may be related. The effect of chronic atropine treatment on the TRH content of several brain areas in Wistar rats was studied. Atropine produced significant increases in TRH content in the preoptic and septal areas, while decreases were observed in the hypothalamus and hypophysis. The concentration of TRH in cerebrospinal fluid rose significantly in atropine-treated rats compared with controls. A similar effect was observed with eserine, an acetylcholinesterase inhibitor. Finally, perfusion of brain preoptic area slices from normal rats with Krebs-Ringer solution in the presence of pilocarpine increased basal TRH release significantly and this effect was blocked by atropine. These results are compatible with a muscarinic control on the activity of the central TRH system.
Assuntos
Encéfalo/metabolismo , Receptores Muscarínicos/metabolismo , Hormônio Liberador de Tireotropina/metabolismo , Animais , Atropina/farmacologia , Hipotálamo/efeitos dos fármacos , Masculino , Perfusão , Fisostigmina/farmacologia , Pilocarpina/farmacologia , Hipófise/efeitos dos fármacos , Área Pré-Óptica/efeitos dos fármacos , Radioimunoensaio , Ratos , Ratos Wistar , Septo Pelúcido/efeitos dos fármacos , Hormônio Liberador de Tireotropina/líquido cefalorraquidianoRESUMO
The effect of chronic atropine treatment was studied on thyrotropin releasing hormone (TRH) content of several brain areas in Wistar rats. Atropine produced TRH increases in the septal area, preoptic area and the hypophysis; this was observed when rats were killed immediately after the last dose, while a decrease was observed only in the hypophysis 48 h after the last atropine dose. TRH concentration in cerebrospinal fluid rose significantly after atropine withdrawal with respect to controls. Treatment with eserine, an acetylcholinesterase inhibitor, produced the same effect. These results indicate cholinergic participation in central TRH regulation.