Effect of 5-aminolevulinic acid (ALA) accumulation on hypertension status

CABALLERO, FABIANA; GUOLO, MARCELO; BATLLE, ALCIRA

Newport, Rhode Island, Estados Unidos

Congreso; GORDON RESEARCH CONFERENCE ON THE CHEMISTRY AND BIOLOGY OF TETRAPYRROLES; 2006

Gordon Research Conferences

The heme precursor ä-aminolevulinic acid (ALA), promotes the generation of reactive oxygen species (ROS). Accumulation of ALA as occurs en acute intermittent porphyria (AIP), produces oxidative cellular damage. Hypertension (HT) is a common sign in 50% of the patients during an acute attack of porphyria. In this work we investigated the effect of ALA accumulation on HT and heme metabolism. Wistar Kyoto rats (WKY, normotensive) and spontaneously hypertensive rats (SHR), 12 weeks old, were chronically intoxicated with ALA (40 mg/kg body weight, ip, 10 doses). We observed that ALA treatment provoked, in hepatic tissues, a diminution of ä-aminolevulinic acid synthase (ALAS) activity (WKY+ALA: 60%; SHR+ALA: 67%) and an increase in HO activity, 83% in WKY+ALA and 62% in SHR+ALA. Both, ä-aminolevulinic acid dehydratase  and deaminase hepatic activities were not affected when compared to the control group (WKY). Lipid peroxidation (TBARS levels) diminished 25% in WKY+ALA and 15% in SHR+ALA while GSH content was slightly enhanced, 15% and 18% respectively. Exposure to ALA in both strains showed that the effects of this precursor are more greater in WKY rats than in SHR rats;  a slightly increment of the arterial blood pressure was observed. From these findings, we would conclude that ALA accumulation would not be a determinant factor for the secondary HT occurring in human hepatic porphyria and suggest that the prooxidant effect of ALA would not be an aggravating factor for the course of essential HT.