Differential effects of dietary cholesterol on aminopeptidase A, B and M in the frontal cortex of male and female mice.

Although hypercholesterolemia and hypertension have been extensively associated, the regulatory mechanism underlying this relationship is poorly understood. Systemic and local renin-angiotensin systems are involved in the control of blood-pressure. Angiotensin II has been considered as the main effector peptide of renin-angiotensin system. However, other peptides derived from the metabolism of angiotensin II, as angiotensins III and IV have been shown to play significant roles. The aim of this study is to analyse the effect of dietary cholesterol on the activity of the enzymes involved in the metabolism of angiotensins II and III. Soluble and membrane-bound aminopeptidase A (aspartyl- and glutamyl-aminopeptidases), B (arginyl-aminopeptidase) and M (alanyl-aminopeptidase) activities were measured in the frontal cortex of male and female mice fed a cholesterol enriched-diet (1% cholesterol; 0.5 cholic acid). Soluble and membrane-bound aminopeptidases B and M did not change in male or female cholesterol groups. Significant increases were observed in membrane-bound aspartyl- and glutamyl-aminopeptidase activities in both cholesterol groups. Soluble aspartyl- and glutamylaminopeptidases did not change in male cholesterol group, but significant decreases were detected in female cholesterol group. Our results may indicate that the metabolism of angiotensin II to angiotensin III by aminopeptidase A is increased, but angiotensin III metabolism by aminopeptidases B and M is not modified after cholesterol intake; so cholesterol may enhance the effects of angiotensin III, at least, at the cortical level.