HEME METABOLISM REGULATION IN HYPERTENSIVE RATS

GUOLO, M; CABALLERO, F; BATLLE, A

Kingston-Upon-Hull, United Kingdom

Congreso; TETRAPYRROLE DISCUSSION GROUP MEETING; 2005

TETRAPYRROLE DISCUSSION GROUP MEETING

. The enzymatic action of heme oxygenase (HO) yields carbon monoxide, biliverdin and iron. Carbon monoxide and HO participate in the homeostatic control of cardiovascular functions, including the regulation of blood pressure. Both deficiency, and excess of HO-1 may be involved in the pathogenesis of arterial hypertension. To examine the effect of hypertension (HT) on heme metabolism regulation we have used two different models of  experimental HT. Wistar rats (100-150 g) were treated with nitro-L-arginine methyl ester (L-NAME) (50 mg/kg/day in drinking water) during a whole period of 8 weeks and age-matched males SHR of the Okamoto-Aoki strain and normotensive WKY originally derived from  Charles River Breeding Farm (Wilmington, Mass) were used. We have measured the hepatic activities of heme enzyme metabolism, ä-aminolevulinic acid synthetase (ALA-S),  ä-aminolevulinate dehydratase (ALA-D), deaminase (DEAM) and HO. In young SHR rats (8 weeks)  the level of ALA-S was 50% increased while HO was 40% decreased; ALA-D was diminished 30%  and DEAM was not altered. In adults SHR rats (20 weeks) ALA-D was  30% decreased; instead the other enzyme activities were within normal values. In L-NAME treated rats ALA-S showed a significant increase of 50% at week 1 and then decreased gradually to reach 25% at week 8. In contrast, HO diminished 45% at week1 recovering a 10% of its activity at week 8. ALA-D was decreased 30% to week 1 recovering basal levels to week 3 while DEAM was diminished from week 3 to reach 20% of inhibition at the end of study period. These results are further evidence on the  sustained heme degradation enzyme behaviour and its implicance in heme regulation during HT and  suggest that chronic treatment with L-NAME would be other model of HT development at week one.