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

FABIANA CABALLERO; MARCELO GUOLO; ALCIRA BATLLE

Newport, Rhode Island, USA

Congreso; 2006 Gordon Research Conference The Chemistry & Biology of Tetrapyrroles; 2006

Gordon Research

Abstract ä-aminolevulinic acid (ALA), an heme precursor, promotes the generation of reactive oxygen species (ROS). Accumulation of ALA as occurs en acute intermittent porphyria (AIP), exert oxidative cellular damage. Hypertension (HT) is a common sign in as many as 50% of the patient 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, received a chronic intoxication 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) activities (WKY+ALA: 60%; SHR+ALA: 70%) and an increase in HO activities, 80% in WKY+ALA and 70% in SHR+ALA. Both, ä- aminolevulinic acid dehydratase (ALAD) and deaminase hepatic activities were not affected respect to control group (WKY). Lipid peroxidation (TBARS levels) diminished 25% in WKY+ALA and 15% in SHR+ALA while GSH content was slightly incremented, 15% and 18% respectively. Exposure to ALA in both strains increase slightly arterial blood pressure; it seems to be associated with prooxidant effect of ALA. Data demonstrated that the effects of ALA chronic treatment are strongly manifested in WKY rats than in SHR rats. From these findings, we could probably conclude that ALA accumulation would not be a determinant factor in the secondary HT occurring in human hepatic porphyria.