The renin-angiotensin system (RAS) plays an important role in the pathophysiology of cardiovascular disease (CVD). ACE (angiotensin-converting enzyme) 2 degrades Ang (angiotensin) II, the main effector of the classic RAS, and generates Ang-(1-7). Thus, ACE2 plays a crucial role in the RAS because it opposes the actions of Ang II. However, the activity of ACE and ACE2 and the relationship between theses enzymes with coronary perfusion pressure (CPP) in male and female spontaneously hypertensive rats (SHR) remain unclear and were our objectives. The procedures 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 hearts were immediately excised. Studies on the coronary vascular bed were performed on whole hearts using a Langendorff preparation for perfused isolated hearts and were perfused with modified Krebs solution, equilibrated with 95% oxygen and 5% carbon dioxide at a controlled pressure of 100 mmHg to give a pH of 7.4. Langendorff preparations were perfused at a rate of 10 mL/min with a peristaltic pump. After the CPP were measured, the coronary were isolated and the ACE and ACE2 activity were evaluated by fluorimetry. Female rats exhibited a higher CPP (125±5 mmHg, p<0.05), ACE (110±15 AFU, p<0.05) and ACE2 (0.1±0.02 AFU, p<0.05) activity than the male rats (CPP: 85±3 mmHg; ACE 60±3 AFU and ACE2 0.06±0.002 AFU). Castration reduced the ACE (32±3 AFU) and CPP (90±5 mmHg) in the female rats but did not affect ACE2 (0.09±0.002), while in the male rats the CPP (145±6 mmHg) and ACE2 (0.03±0.001 AFU) were increased and ACE (46±5 AFU) activity was reduced. One of the main findings of this study was the observation of sex dimorphisms among CPP, ACE and ACE2 activity and the different relationship of RAS on CPP in SHR, dependent of the sex. In female SHR the CPP is associated with ACE, while in male rats is with ACE2 activity. The present results may contribute to understand the sex differences in the regulation of cardiovascular system and the incidence of cardiovascular disease in women.
37th Congress of IUPS (Birmingham, UK) (2013) Proc 37th IUPS, PCB012
Poster Communications: Coronary perfuse pressure is associated with angiotensin-converting enzyme (ACE) in female and with ACE2 activity in male SHR.
N. Bissoli1, P. L. Dalpiaz1, S. G. Figueiredo1, A. Lamas1, I. F. Caliman1, A. Medeiros2, T. Andrade3, M. Alves4, A. K. Carmona4, W. Gonçalves5, M. Moysés1
1. UFES, Vit¾ria, Brazil. 2. Federal Institute of Espirito Santo, Vila Velha, Brazil. 3. Department of Pharmacy, University Vila Velha, Vila Velha, Brazil. 4. Department of Biophysics, Escola Paulista de Medicina, Federal University of SÒo Paulo, SÒo Paulo, Brazil. 5. UNESC, Colatina, Brazil.
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Where applicable, experiments conform with Society ethical requirements.