Sex differences exist in brain renin-angiotensin system-regulating aminopeptidase activities in transplacental ethyl-nitrosourea-induced gliomas

Introduction: The renin angiotensin system (RAS) is emerging as an important target for the treatment of glioma. We had described that the local RAS is involved in vivo in tumor growth in the rat model of experimental C6 glioma implanted at the subcutaneous region, through the modification of several proteolytic regulatory enzymes of aminopeptidase type. Methods: We analyze RAS-regulating aminopeptidase activities in plasma and brain tissue of control male and female rats and rats with transplacental ethylnitmsourea-induced gliomas. Results: No differences were found either the mean total number of tumors per animal or the tumor volume between male and female animals. However, we have found increased levels in aspartyl aminopeptidase in both males and females and of aminopeptidase B only in males. On the contrary, decreased levels were found in aminopeptidase N and insulin-regulated aminopeptidase activities in both males and females, whereas aminopeptidase A only decreased in females. Decreased levels of aminopeptidase N, aminopeptidase B and insulin-regulated aminopeptidase were also shown in plasma of only female rats. Conclusions: Under the complexity of RAS cascade, the changes found suggest the predominant actions of angiotensin III against a decreased action of angiotensin II and angiotensin IV. We conclude that angiotensin peptides are involved in tumor growth in this rat model of glioma and that their role in tumor growth can be analyzed through their corresponding proteolytic regulatory enzymes, which make them new and attractive therapeutic targets beyond the use or angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs).

Automated summary

The study showed that the renin angiotensin system plays a role in tumor growth in the rat model of glioma, with increased levels of aspartyl aminopeptidase and aminopeptidase B activities, as well as decreased levels of aminopeptidase N, aminopeptidase A, and insulin-regulated aminopeptidase activities. These findings suggest the predominant actions of angiotensin III against a decreased action of angiotensin II and IV in tumor growth.