Oral L-histidine exerts antihypertensive effects via central histamine H3 receptors and decreases nitric oxide content in the rostral ventrolateral medulla in spontaneously hypertensive rats.
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.
Toba
Hiroe
H
Department of Clinical Pharmacology, Division of Pathological Sciences, Kyoto Pharmaceutical University, Kyoto, Japan. toba@mb.kyoto-phu.ac.jp
Nakamori
Ayako
A
Tanaka
Yoshimi
Y
Yukiya
Ryosuke
R
Tatsuoka
Keisuke
K
Narutaki
Masako
M
Tokitaka
Masaaki
M
Hariu
Hitoshi
H
Kobara
Miyuki
M
Nakata
Tetsuo
T
D000284:Administration, Oral; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D006632:Histamine / Q000134:cerebrospinal fluid; D017442:Histamine Agonists / Q000494:pharmacology; D006633:Histamine Antagonists / Q000494:pharmacology; D006639:Histidine / Q000008:administration & dosage / Q000494:pharmacology*; D007276:Injections, Intraventricular; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects* / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D009638:Norepinephrine / Q000652:urine; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D010880:Piperidines / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D018100:Receptors, Histamine H3 / Q000187:drug effects*; D014666:Vasomotor System / Q000187:drug effects
D000959:Antihypertensive Agents; D017442:Histamine Agonists; D006633:Histamine Antagonists; D010880:Piperidines; D018100:Receptors, Histamine H3; D009569:Nitric Oxide; D006639:Histidine; D006632:Histamine; D007703:Peptidyl-Dipeptidase A; C052075:thioperamide; D009638:Norepinephrine