Postnatal Ontogeny of Angiotensin Receptors and ACE2 in Male and Female Rats

• Published in: Gender medicine 2012-02, Vol.9 (1), p.21-32
• Main Authors: Sampson, Amanda K., PhD, Moritz, Karen M., PhD, Denton, Kate M., PhD
• Format: Article
• Language: English
• Subjects: Angiotensin I - genetics; Angiotensin I - metabolism; angiotensin receptors; angiotensin-converting enzyme 2; Animals; Biological and medical sciences; Female; Gene Expression; gene expression/regulation; heart; Internal Medicine; kidney; Kidney - metabolism; Male; Medical sciences; Miscellaneous; Peptide Fragments - genetics; Peptide Fragments - metabolism; Peptidyl-Dipeptidase A - genetics; Peptidyl-Dipeptidase A - metabolism; Public health. Hygiene; Public health. Hygiene-occupational medicine; Rats; Rats, Sprague-Dawley; Receptor, Angiotensin, Type 1 - genetics; Receptor, Angiotensin, Type 1 - metabolism; Receptors, Angiotensin - genetics; Receptors, Angiotensin - metabolism; RNA, Messenger - metabolism; sex differences; Sex Factors
• ISSN: 1550-8579; 1878-7398
• DOI: 10.1016/j.genm.2011.12.003

Abstract Background Sex differences in the expression of the angiotensin (Ang) II receptors and angiotensin-converting enzyme 2 (ACE2) have been hypothesized to be a potential mechanism contributing to sex-specific differences in arterial pressure. Currently, sex differences in the expression of the angiotensin receptors and ACE2 remain undefined. Objectives The aim of this study was to define the postnatal ontogeny of mRNA expression, from birth to adulthood, of the Ang II and Ang-(1-7) receptors and ACE2 in male and female rats. Methods Kidney and heart tissue was collected from male and female Sprague Dawley rats and snap-frozen at postnatal days (PNDs) 1, 30, 42, 70, and 110 (adult), and real-time polymerase chain reaction was performed to determine relative expression of the Ang II and Ang-(1-7) receptors (AT1a R, AT1b R, AT2 R, and MasR) and ACE2. Results All these components of the renin-angiotensin system (RAS) were detected in the kidney and left ventricle, although expression levels differed significantly between the sexes and across organs. Gene expression of most components of the RAS was high at birth and decreased with age in both sexes, except for ACE2 expression, which increased in the left ventricle with age ( PAge < 0.001). Low levels of AT2 R were observed in the ventricles in both sexes as adults. Most notably, AT2 R expression was greatest in female kidneys and lowest in male kidneys compared with the left ventricle ( PAge*Sex < 0.05). Interestingly, MasR expression in the female kidney was similar to the level of AT2 R expression. Left ventricular MasR expression was greater than AT2 R expression in both sexes but was not different between the sexes. The highest level of ACE2 expression was observed in adult female kidneys ( PAS < 0.05). Conclusions The enhanced mRNA expression of the vasodilatory arm of the renal RAS (ACE2, AT2 R) in females observed in the present study may contribute to sex differences in the regulation of arterial pressure and the incidence of cardiovascular disease in women.