Does brain histamine contribute to the development of hypertension in spontaneously hypertensive rats?
Histaminergic neurons of the brain have been implicated in genetic hypertension. We investigated the effect of inhibition of histamine synthesis by alpha-fluoromethylhistidine (alpha-FMH), the irreversible inhibitor of histidine decarboxylase, on the development and maintenance of hypertension in spontaneously hypertensive rats. Young (3-week-old) and adult (7-week-old) rats were treated with alpha-fluoromethylhistidine for 29 and 13 days, respectively. Treatment of spontaneously hypertensive rats and normotensive Wistar-Kyoto rats with alpha-fluoromethylhistidine led to a pronounced decrease in the histidine decarboxylase activity and in the histamine concentration in the brain (hypothalamus, brainstem, cortex-midbrain). In adult spontaneously hypertensive rats, the development of hypertension was not influenced by alpha-fluoromethylhistidine. In young spontaneously hypertensive rats, alpha-fluoromethylhistidine led to a transient delay in the development of hypertension which was followed by a transient tendency to increased blood pressure. It is concluded that histaminergic neurons of the brain play only a subordinate role, if any at all, in the development of hypertension in spontaneously hypertensive rats.
Prast
H
H
Institut für Pharmakodynamik und Toxikologie der Universität, Innsbruck, Austria.
Philippu
A
A
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000378:metabolism*; D001923:Brain Chemistry; D001933:Brain Stem / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D006632:Histamine / Q000096:biosynthesis* / Q000502:physiology; D006640:Histidine Decarboxylase / Q000037:antagonists & inhibitors / Q000378:metabolism; D006973:Hypertension / Q000209:etiology*; D007031:Hypothalamus / Q000378:metabolism; D008636:Mesencephalon / Q000378:metabolism; D008762:Methylhistidines / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
D008762:Methylhistidines; C028309:alpha-fluoromethylhistidine; D006632:Histamine; D006640:Histidine Decarboxylase