Effect of the heme/heme oxygenase pathway on the relationship between salt consumption and blood pressure.

ABSTRACT

OBJECTIVE: Some studies have shown that heme oxygenase inhibition increases blood pressure in rats. This effect may be due to the consequent lower levels of the heme degradation products (carbon monoxide, biliverdin, and Fe3+) or due to heme accumulation. However, it is not yet known if the variable effect of NaCl on blood pressure levels is influenced by the heme/heme oxygenase pathway activity. This enzymatic system may be studied by blocking its activity with zinc protoporphyrin IX (ZnPP IX), a heme oxygenase inhibitor. DESIGN AND METHODS: Male Wistar rats were fed from weaning with low (LSD--0.15% NaCl), normal (NSD--1.3% NaCl), or high (HSD--8% NaCl) salt diet On the 12th week of age, assessment of the tail-cuff blood pressure (tc-BP) response to acute inhibition of heme oxygenase with ZnPP IX or after vehicle (Na2CO3) was performed. RESULTS: A higher tc-BP was observed on HSD both before ZnPP IX (P< 0.001) and vehicle (P = 0.003). After ZnPP IX, tc-BP decreased on HSD (P < 0.001) and increased on NSD (P = 0.003) and on LSD (P < 0.001). The area under the curve (AUC) of the percentage change in the blood pressure response was calculated. On putting all the rats from the three dietary groups together, an inverse correlation was observed between individual AUC after ZnPP IX and control tc-BP (r = -0.71; P< 0.001) but not after vehicle (r = 0.34; P < 0.05). CONCLUSIONS: Chronic salt overload increases blood pressure in Wistar rats and the pressure response to heme oxygenase is modulated by the effect of NaCl consumption on blood pressure levels.