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

Clin Exp Pharmacol Physiol. 2010 Jan;37(1):62-8. doi: 10.1111/j.1440-1681.2009.05227.x.


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.

MeSH terms

  • Administration, Oral
  • Animals
  • Antihypertensive Agents / administration & dosage
  • Antihypertensive Agents / pharmacology*
  • Aorta / drug effects
  • Aorta / metabolism
  • Blood Pressure / drug effects
  • Histamine / cerebrospinal fluid
  • Histamine Agonists / pharmacology
  • Histamine Antagonists / pharmacology
  • Histidine / administration & dosage
  • Histidine / pharmacology*
  • Injections, Intraventricular
  • Male
  • Medulla Oblongata / drug effects*
  • Medulla Oblongata / metabolism
  • Nitric Oxide / metabolism*
  • Norepinephrine / urine
  • Peptidyl-Dipeptidase A / metabolism
  • Piperidines / administration & dosage
  • Piperidines / pharmacology
  • Rats
  • Rats, Inbred SHR
  • Rats, Inbred WKY
  • Receptors, Histamine H3 / drug effects*
  • Vasomotor System / drug effects


  • Antihypertensive Agents
  • Histamine Agonists
  • Histamine Antagonists
  • Piperidines
  • Receptors, Histamine H3
  • Nitric Oxide
  • Histidine
  • Histamine
  • Peptidyl-Dipeptidase A
  • thioperamide
  • Norepinephrine