Caballero F.A., Guolo M.N., Batlle A
CIPYP (CONICET-UBA), Buenos Aires, Argentina
Heme oxygenase (HO) is the rate-limiting enzyme in heme catabolism. HO and carbon monoxide (CO) participate in homeostatic control of cardiovascular functions, including the regulation of blood pressure (BP). Upregulation of HO has been shown to lower BP in young (8 weeks) but not in adult (20 weeks) spontaneously hypertensive rats (SHR), the animal model of human essential hypertension (HT). The aim of this study has been to examine the heme metabolism during the development of HT. Age-matched male SHR of the Okamoto-Aoki strain and normotensive WKY originally derived from Charles River Breeding Farm (Wilmington, Mass) were used. In young SHR rats (8 weeks), the level of δ-aminolevulinic synthetase (ALA-S) was 50% increased while HO was 45% decreased in liver. The blood activities of δ-aminolevulinate dehydratase (ALA-D) and deaminase were not affected, hepatic ALA-D was 30% decreased. In adults SHR rats (20 weeks) the blood and hepatic ALA-D activities were decreased 40% and 30%, respectively. Instead the levels of other enzymatic activities were within normal values. The plasma porphyrin index (PPI) was 200% enhanced in young SHR, but normal in SHR adults rats. The 24-h urinary porphyrin excretion was similar in WKY and SHR rats. However, the pattern gradually changed during the different stages of HT, showing an increase of uroporphyrin that correlated with BP values. These heme metabolism disturbances occurring during HT might be attributed to the pathogenic mechanisms involved in the development of hypertension.