The roles of Angiotensin-Converting Enzyme (ACE) inhibitors in treating arterial hypertension, congestive heart failure, and other cardiovascular diseases have been documented well. However, recent study as well as research has shown that treating patients with appropriate doses of ACE inhibitors did not result in permanent attenuation Angiotension plasma levels (Daugherty et al. 2000).Angiotensin-2 generation by ELA-2 was checked in both in-vivo and ex-vivo mesenteric hearts. However, the role of ELA-2 is in-vivo regulation of the cardiac cycle by bringing about alternative constriction and relaxation of the arterioles in debatable (Becari et al. 2017).In order to arrive at a suitable conclusion knockout mouse for ELA-2 gene was compared with a wild type mouse. Test such as echocardiography was used to access cardiac output, stroke volume. Moreover, cardiac indexes, ventricular wall thickness, ventricular areas along with collagen density were studied histologically (Daugherty et al. 2000).The ELA-2 knockout mice depicted symptoms of bradycardia, which could be related to the mutation caused in the gene synthesizing Elastase-II. This could be related to the decrease in the cardiac inhibitory function of Angiotensin –II on parasympathetic function (Winkelmayer et al. 2006).
Angiotension II in promoting atherosclerotic lesions
Increased plasma concentrations of Angiotension could be related to development of atherosclerotic lesions. The lesions were majorly lipid-laden macrophages and lymphocytes (Daugherty et al. 2000).Further conduct of study pointed at increased concentration of Angiotensin-2 can have profound effect on the vascular pathology in combination with the phenomenon of Hyperlipidemia (Liu et al. 2015).Reports and studies have supported that in humans increased cardiac functions have been noted with increase in the rate of rennin, which is the rate-limiting step in Angiotensin –II generation (Becari et a l. 2017).The injection or administrations of ACE inhibitors have been associated with decreased rate of cardiac morbidity. Evidence suggests that atherosclerotic lesions expressing the enzymes necessary for Ang II include rennin and ACE (Winkelmayer et al. 2006).Studies have shown that abnormal Ang –II may increase the atherogenic process by increasing the rate of arterial blood pressure. Moreover, increased concentrations of Angiotension –II in the plasma could be linked to the activation of monocytes and macrophages and increased oxidative stress. All these factors could be linked with promotion of atherosclerosis (Ponnuswamy et al. 2017).
Angiotension converting enzyme
- The Angiotensin Converting Enzyme was clinically introduced to regulate the concentration of Renin-Angiotensin-Aldosterone in blood. Reports have shown increased concentration to be related with the rate of cardiovascular morbidity and hypertension (Daugherty et al. 2000).
- ACE inhibitors have shown to reduce ventricular hypertrophy, albumineria and arterial damage. Thus, increasing longevity and decreasing the rate of development of abnormal cardiovascular conditions.
- Reports have also suggested that ACE prevent breakdown of Bradykinin a potential nitric oxide releasing factor. The Nitric Oxide plays a pivotal role in attenuation of the endothelial function (Zhang et al. 2015).
- The ACE inhibitors have been shown to reduce target organ damage by maintaining a balance in the sympathovagal system. Studies have shown that the ACE inhibitors can promote antiatherogenetic effects by promoting fibrinolysis and thrombogenesis (Ponnuswamy et al. 2017).
For the present assessment, a number of articles have been referenced explaining the effects of increased plasma concentration of Angiotensin and its effect in the maintenance of the cardiovascular health. I think the article presented by Winkelmayer et al. (2006), is rather well documented, where the effect of Elastace has been compared in a wild types mouse with that of a Knockout mice for Elastase-2. This could be related to decrease in the cardiac inhibitory function of the Angiotensin-2 on the parasympathetic nervous system. Thus, MI could be associated with increased activation of RAS. Thus, heart failure has been linked with hyperactivity of RAS, which further increases the concentration of plasma levels of Angiotesnin. The Angiotensin levels need to be checked via the Angiotensin Converting Enzyme (ACE). The angiotensin-converting enzyme reduces the rate of heart activity by activating the parasympathetic system. It has been well explained via the sympathetic vagal balance, which has been disrupted in the mice suffering Myocardial infarction. In this respect, deletion of the ELA-2 gene decreased the basal heart rate of the mice. This proved that the same might be responsible for controlling the cardiac morbidities in the rats. The study helps in presentation of a comparative analysis where hyperactive concentration of Angiotensin have been seen to promote the rate of atherogenesis. This presents a debatable area where the use of ACE in the treatment of cardiovascular disease has been challenged
Becari, C., Durand, M. T., Guimaraes, A. O., Lataro, R. M., Prado, C. M., de Oliveira, M., … Salgado, H. C. (2017). Elastase-2, a Tissue Alternative Pathway for Angiotensin II Generation, Plays a Role in Circulatory Sympathovagal Balance in Mice. Frontiers in Physiology, 8, 170. https://doi.org/10.3389/fphys.2017.00170
Daugherty, A., Manning, M. W., & Cassis, L. A. (2000). Angiotensin II promotes atherosclerotic lesions and aneurysms in apolipoprotein E–deficient mice. Journal of Clinical Investigation, 105(11), 1605–1612.
Liu, C. L., Wang, Y., Liao, M., Wemmelund, H., Ren, J., Fernandes, C., ... & Zhang, J. Y. (2015). Allergic Lung Inflammation Aggravates Angiotensin II–Induced Abdominal Aortic Aneurysms in Mice. Arteriosclerosis, thrombosis, and vascular biology, ATVBAHA-115.
Ponnuswamy, P., Joffre, J., Herbin, O., Esposito, B., Laurans, L., Binder, C. J., ... & Zhang, Y. (2017). Angiotensin II synergizes with BAFF to promote atheroprotective regulatory B cells. Scientific Reports, 7.
Winkelmayer, W. C., Fischer, M. A., Schneeweiss, S., Levin, R., & Avorn, J. (2006). Angiotensin Inhibition After Myocardial Infarction: Does Drug Class Matter? Journal of General Internal Medicine, 21(12), 1242–1247. https://doi.org/10.1111/j.1525-1497.2006.00590.x
Zhang, X., Thatcher, S., Wu, C., Daugherty, A., & Cassis, L. A. (2015). Castration of male mice prevents the progression of established angiotensin II-induced abdominal aortic aneurysms. Journal of vascular surgery, 6