Abstract-The early and long-term effects of coronary artery ligation on the plasma and left ventricular angiotensinconverting enzyme (ACE and ACE2) activities, ACE and ACE2 mRNA levels, circulating angiotensin (Ang) levels [Ang I, Ang-(1-7), Ang-(1-9), and Ang II], and cardiac function were evaluated 1 and 8 weeks after experimental myocardial infarction in adult Sprague Dawley rats. Sham-operated rats were used as controls. Coronary artery ligation caused myocardial infarction, hypertrophy, and dysfunction 8 weeks after surgery. At week 1, circulating Ang II and Ang-(1-9) levels as well as left ventricular and plasma ACE and ACE2 activities increased in myocardial-infarcted rats as compared with controls. At 8 weeks post-myocardial infarction, circulating ACE activity, ACE mRNA levels, and Ang II levels remained higher, but plasma and left ventricular ACE2 activities and mRNA levels and circulating levels of Ang-(1-9) were lower than in controls. No changes in plasma Ang-(1-7) levels were observed at any time. Enalapril prevented cardiac hypertrophy and dysfunction as well as the changes in left ventricular ACE, left ventricular and plasmatic ACE2, and circulating levels of Ang II and Ang-(1-9) after 8 weeks postinfarction. Thus, the decrease in ACE2 expression and activity and circulating Ang-(1-9) levels in late ventricular dysfunction post-myocardial infarction were prevented with enalapril. These findings suggest that in this second arm of the renin-angiotensin system, ACE2 may act through Ang-(1-9), rather than Ang-(1-7), as a counterregulator of the first arm, where ACE catalyzes the formation of Ang II. Key Words: angiotensin-converting enzyme Ⅲ myocardial infarction Ⅲ renin-angiotensin system Ⅲ remodeling Ⅲ cardiac function T he renin-angiotensin system (RAS) is a more complex system than originally thought. A new angiotensin-converting enzyme (ACE), ACE2, has been recently identified as a homologue of ACE. 1 ACE2 is also a metalloprotease consisting of 805 amino acids with a considerable degree of homology to ACE (40% identity and 61% similarity). 2,3 ACE2 contains a single zinc-binding domain and is a carboxypeptidase, unlike somatic ACE, which contains 2 zinc-binding domains and is a dipeptidyl carboxypeptidase. 2 Both ACE2 and ACE are bound to the plasma membrane and must be cleaved to release the soluble enzyme. 2 Their cellular and tissue distributions are also different, in that ACE is expressed in the endothelium throughout the vasculature, whereas ACE2 is distributed to most tissues, including to the heart and kidney. 3 Analyses in vitro have shown that ACE2 cleaves angiotensin (Ang) I to Ang-(1-9), which is then cleaved by ACE to Ang-(1-7). However, ACE2 also cleaves Ang II to form Ang-(1-7). Because Ang-(1-7) is a potent vasodepressor peptide, its actions could counterbalance the vasopressor effect of Ang II. 4,5 ACE2 does not act on bradykinins and its activity is not inhibited by ACE inhibitors. 2 Although a significant activation of the RAS system occurs after myocardial infarction, 6 -10 ...

Angiotensin-(1-9) is an effective and a novel anti-cardiac hypertrophy agent not acting via the Mas receptor.

Angiotensin-(1-9) reduces hypertension, ameliorates structural alterations (hypertrophy and fibrosis), oxidative stress in the heart and aorta and improves cardiac and endothelial function in hypertensive rats. These effects were mediated by the AT2 receptor but not by the angiotensin-(1-7)/Mas receptor axis.

In experimental hypertension, Rho-associated, coiled-coil containing protein kinase (ROCK) inhibition reduces blood pressure and increases ACE2 levels and activity. At the same time, ROCK inhibition reduces angiotensin II and increases Ang-(1-9) plasma levels. Fasudil also increases vascular eNOS mRNA levels and reduces aortic overexpression of the remodeling promotion proteins TGF-β1, PAI-1, and MCP-1. This effect might additionally contribute to the antihypertensive and antiremodeling effects of ROCK inhibition in hypertension.

Menores niveles tisulares de la enzima convertidora de angiotensina I homóloga (eca-2) y angiotensina-(1-9) están asociados a mayor remodelamiento de la pared aórtica de ratas hipertensas

Atrial fibrillation (AF) is prevalent arrhythmia in adult population. Inflammation is a risk factor for AF and might have important in its occurrence. Increased C‐reactive protein plasma levels (CRP) have been found in AF and they could be determined by polymorphisms in the CRP gene. We investigate here if the G219A polymorphism in CRP gene is associated to AF occurrence. In this study, 116 patients with elective CABG were included. Systemic inflammatory markers were measured at baseline and 72 h after surgery. G219A polymorphism in the CRP gene, located 219‐bp downstream of exon 2 in the 3′ flanking sequence, was determined by PCR and we correlated with plasma CPR levels and AF occurrence. This study was approved by the Ethics Committee of each participating health center. All patient gave signed an informed consent. Mean age of patients was 61±11 years and 85% of them were male and 48% had a history of hypertension. Allelic frequencies for allele G and A were 0.57 and 0.43, respectively. There were no differences between genotypes with regard to diagnosis, risk factors, smoking, medical history and medications at entry. Postoperative FA incidence was 13%. Mean preoperative and postoperative PCR levels were 3.35 and 75.6 mg/L, respectively. We concluded that no association between G219A polymorphism in the CRP gene, CRP levels and AF were found.DI‐06‐09‐2, FONDECYT 1070641