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Clin Exp Pharmacol Physiol ; 37(1): 62-8, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19566844

RESUMO

1. L-histidine is generally found in meat, poultry and fish. To investigate its effects on blood pressure, L-histidine was administered to 9-week-old spontaneously hypertensive rats (SHR). 2. Oral administration of L-histidine (100 mg / kg) increased histamine content in cerebrospinal fluid and reduced mean arterial pressure (MAP) in SHR. Intracerebroventricular injection of L-histidine (0.01 microg / 5 microL) also caused a decrease in MAP, which was reversed by cotreatment with the histamine H3 receptor antagonist thioperamide (20.4 microg / 5 microL, i.c.v.). There was a significant, time-dependent increase (over 6 h) in the NOx (NO2- + NO3-) content of the dialysate from the rostral ventrolateral medulla (RVLM), a major vasomotor centre, after oral administration of L-histidine. 3. In another experiment, SHR were treated with l-histidine (100 mg / kg) twice a day for 4 weeks. Chronic treatment with L-histidine inhibited the age-dependent increases in systolic blood pressure and urinary noradrenaline excretion seen in vehicle-treated SHR. Conversely, intracerebroventricular injection of thioperamide (20.4 microg / 5 microL, i.c.v.) reversed the decrease in MAP in response to L-histidine in SHR. 4. Reverse transcription-polymerase chain reaction analysis revealed that the aortic expression of angiotensin-converting enzyme mRNA was suppressed by chronic treatment with L-histidine. 5. These results suggest that L-histidine decreases blood pressure by attenuating sympathetic output via the central histamine H3 receptor in SHR. In addition, the antihypertensive effects of L-histidine appear to be associated with an increase in nitric oxide in the RVLM.


Assuntos
Anti-Hipertensivos/farmacologia , Histidina/farmacologia , Bulbo/efeitos dos fármacos , Óxido Nítrico/metabolismo , Receptores Histamínicos H3/efeitos dos fármacos , Administração Oral , Animais , Anti-Hipertensivos/administração & dosagem , Aorta/efeitos dos fármacos , Aorta/metabolismo , Pressão Sanguínea/efeitos dos fármacos , Histamina/líquido cefalorraquidiano , Agonistas dos Receptores Histamínicos/farmacologia , Antagonistas dos Receptores Histamínicos/farmacologia , Histidina/administração & dosagem , Injeções Intraventriculares , Masculino , Bulbo/metabolismo , Norepinefrina/urina , Peptidil Dipeptidase A/metabolismo , Piperidinas/administração & dosagem , Piperidinas/farmacologia , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Sistema Vasomotor/efeitos dos fármacos
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