Male spontaneously hypertensive rats (SHR) had a higher systolic blood pressure than female SHR. Previous studies have shown that castration lowered the blood pressure of male rats and can increase in female SHR. Differences between males and females have been found in components of the renin-angiotensin system (RAS) and these differences can be associate to sexual dimorphism in hypertension development. However, the activity of angiotensin-converting enzyme (ACE) and ACE2 in male and female SHR remain unclear. Therefore, this study was designed to investigate whether: 1) there are sex differences in ACE and ACE2 in the kidney in spontaneous hypertension; 2) sex hormones play a role in these sex differences. The procedures were carried out in compliance with the guidelines for the ethical use of animals in scientific research and were approved by the Ethical Committee of the Federal University of Espírito Santo (023/2009). Female and male SHR rats were divided into 4 experimental groups: sham and castrated. After 51 days of the castration, the rats were anesthetized with ketamine (70 mg/kg i.p.) and xylazine (10 mg/kg i.p.) and their kidneys were immediately excised and the ACE and ACE2 activity were evaluated by fluorimetry. Female rats exhibited a higher ACE (25±1 AFU, p<0.05) and ACE2 (0.15±0.002 AFU, p<0.05) activity than the male rats (ACE 17±3 AFU and ACE2 0.02±0.002 AFU), but female rats have more favorable ACE2/ACE ratio (0.006±0.001, p<0.05) than male (0.001±0.0001) rats. Castration did not affect the ACE activity in both sex (female 23±3 and male 16±2 AFU) but decreased ACE2 in the female rats (0.03±0.002 AFU, p<0.05), while increased in the male rats (0.14±0.001 AFU, p<0.05). The castration change the ACE2/ACE ratio in both sex, male rats (0.009±0.001, p<0.05) replaced by more favorable ratio than female (0.0012±0.0002). In conclusion, this study identified sexual dimorphisms among the ACE and ACE2 activity in SHR; sex hormones differentially modulate ACE2 activity. The higher ratio of the renal RAS (ACE2/ACE) in females observed in the present study may contribute to sex differences in the regulation of arterial pressure in SHR and can affect on the severity and the progression of renal disease, that is more rapid in men compared with women.
37th Congress of IUPS (Birmingham, UK) (2013) Proc 37th IUPS, PCC331
Poster Communications: Sex hormones differentially modulate angiotensin-converting enzyme 2 (ACE2) activity in kidney of spontaneously hypertensive rats
P. M. Dalpiaz1, A. S. de Medeiros Garcia2, A. Z. Lamas1, I. F. Caliman1, G. R. Abreu1, T. U. Andrade3, M. F. Alves4, A. K. Carmona4, S. G. Figueiredo1, N. S. Bissoli1
1. Department of Physiological Sciences, Federal University of Espirito Santo, Vitoria, EspÝrito Santo, Brazil. 2. Biological and Health Sciences, Federal Institute of Education, Science and Technology, Vila Velha, EspÝrito Santo, Brazil. 3. Department of Pharmacy, University Vila Velha, SÒo Paulo, EspÝrito Santo, Brazil. 4. Department of Biophysics, Federal University of SÒo Paulo, SÒo Paulo, SÒo Paulo, Brazil.
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Where applicable, experiments conform with Society ethical requirements.