Alpha-fluoromethylhistidine, an inhibitor of histamine biosynthesis, causes arterial hypertension.
In this study we assessed the cardiovascular response to 13 days of irreversible inhibition of the enzyme histidine-decarboxylase (HD) with alpha-fluoro-methylhistidine (AFMH). Age-matched untreated rats were used as controls, Tail-cuff mean arterial pressure (MAP) and heart rate (HR) rose progressively in AFMH-treated rats, reaching maximal values during the study period by the 13th day of treatment. There was a reduction in urinary histamine at the day 7 and 13, and of sodium excretion at the day 7 of treatment, while the renal catecholamine excretion was increased at both days of treatment, suggesting an increase of sympathetic activity. At the 13th day of treatment, there was an activation of the renin-angiotensin-aldosterone system. In addition, the cardiovascular responses to footshock stress were determined in rats treated intraperitoneally (i.p.) or intracerebroventricularly (i.v.t.) with a single dose of AFMH. Peripheral sympathetic facilitation was found, as the hemodynamic response to footshock stress was significantly enhanced after i.p. administration, but not after i.v.t. administration of AFMH. Our results suggest that conditions of peripheral histamine deficiency may result in sympathetic facilitation, arterial hypertension and tachycardia in the rat.
Campos
H A
HA
Department of Pharmacology, J.M. Vargas School of Medicine, Universidad Central de Venezuela, Caracas, Venezuela.
Acuña
Y
Y
Magaldi
L
L
Israel
A
A
D000450:Aldosterone / Q000097:blood; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects*; D002395:Catecholamines / Q000652:urine; D006339:Heart Rate / Q000187:drug effects*; D006632:Histamine / Q000097:blood / Q000652:urine; D006640:Histidine Decarboxylase / Q000037:antagonists & inhibitors*; D006973:Hypertension / Q000139:chemically induced*; D008297:Male; D008762:Methylhistidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012083:Renin / Q000097:blood; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology; D013610:Tachycardia / Q000139:chemically induced*
D002395:Catecholamines; D008762:Methylhistidines; D000450:Aldosterone; C028309:alpha-fluoromethylhistidine; D006632:Histamine; D012083:Renin; D006640:Histidine Decarboxylase