ACE2, a close homologue of ACE, functions as a negative regulator of the angiotensin system and was identified as a key receptor for SARS severe acute respiratory syndrome coronavirus infections. Thus, the RAS appears to play a critical role in the pathogenesis of acute lung injury. Indeed, increasing ACE2 activity might be a novel approach for the treatment of acute lung failure in several diseases. After the discovery of N- and C-domains of ACE, specific domain inhibitors were developed to increase specificity.
Ang I is mainly hydrolyzed by the C-domain in vivo but BK is hydrolyzed by both domains. By developing a C-domain selective inhibitor RXPA some degradation of BK by the N-domain would be permitted and this degradation could be enough to prevent accumulation of excess BK causing angioedema [8].
ACE also acts on other natural substrates including encephalin, neurotensin, and substance P. Besides being involved in blood pressure control, ACE possesses widespread functions including renal development, male fertility, hematopoiesis, erythropoiesis, myelopoiesis, and immune responses [1]. ACE-knockout mice display normal blood pressure under normal conditions, but are sensitive to changes in blood pressure such as exercise.
ACE-knockout also affects renal function, renal development, serum and urine electrolyte composition, haematocrit, and male reproductive capacity [10]. Deficiency in testis ACE affects male fertility but its exact role is still not clear. Although mice with testis ACE deficiency mate normally and their sperm quantity and motility are no different from those of wild-type mice, the survival of sperm in the oviduct and fertilization rate are highly reduced [1].
Overexpression of ACE2 in hypertensive models, but not in normotensive animals, reduced blood pressure. ACE2-knockout mice displayed progressive cardiac dysfunction resembling that of long-term hypoxia after coronary artery disease or bypass surgery in human, which could be reversed by concurrent ACE-knockout.
Inclusion II or deletion DD of bp Alu repeats in the 16th intron affects the human plasma ACE levels and the DD genotype was more frequently found in patients with myocardial infarction but no convincing evidence was available on the association of the DD genotype with hypertension [4]. Not only has ACE2 facilitated the invasion of SARS virus for rapid replication, but also ACE2 is depleted from the cell membrane and therefore the damaging effects of Ang II are enhanced, resulting in acute deterioration of lung tissues.
ACE has been the target of hypertension control since the s. ACE inhibitors are prescribed as the sole or combinational treatment of high blood pressure, for the dual effects of lowering Ang II and slowing down BK degradation. In human hypertensive patients, ACE2 levels are lower in both kidney and heart compared to normotensive volunteers.
M2 gluzincin family domains are shaded. The unrooted phylogenetic tree of the angiotensin converting enzyme ACE and angiotensin converting enzyme 2 ACE2 was constructed with the maximum likelihood method using full-length sequences from representative vertebrate species.
The numbers on the branches indicate the bootstrap values from 1, replicates. National Center for Biotechnology Information , U. Handbook of Hormones. Published online Sep 4. Marty K. Copyright and License information Disclaimer.
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Abstract Angiotensin converting enzyme ACE is well known for its dual actions in converting inactive Ang I to active Ang II and degrade active bradykinin BK , which play an important role in the control of blood pressure. Keywords: angiotensin converting enzyme, angiotensin converting enzyme inhibitor, captopril, hypertension, severe acute respiratory syndrome SARS. Discovery ACE was discovered in the mids by the observation that dialysis of plasma and kidney extract with water and saline before incubation had produced two separate pressor substances, Ang I and Ang II respectively [1].
Open in a separate window. Figure 29D. Distribution of mRNA Somatic ACE is expressed in various tissues including blood vessels, kidney, intestine, adrenal gland, liver, and uterus, and is especially abundant in highly vascular organs such as retina and lung.
Regulation of Synthesis and Release Expression of ACE is affected by steroids and thyroid hormone, but the details of the regulation are not clear. Receptors None. Phenotype in Gene-Modified Animals ACE-knockout mice display normal blood pressure under normal conditions, but are sensitive to changes in blood pressure such as exercise. The overall effect of angiotensin II is to increase blood pressure, body water and sodium content.
Angiotensin II has effects on:. An increase in renin production occurs if there is a decrease in sodium levels and a decrease in blood pressure, which is sensed by the kidneys. In addition, low blood pressure can stimulate the sympathetic nervous system to increase renin production, which results in increased conversion of angiotensinogen to angiotensin I, and so the cycle continues.
On the other hand, natriuretic peptides produced in the heart and central nervous system can impede the renin—angiotensin system in order to increase sodium loss in the urine. Too much angiotensin II is a common problem resulting in excess fluid being retained by the body and, ultimately, raised blood pressure.
This often occurs in heart failure where angiotensin is also thought to contribute to growth in the size of the heart. To combat these adverse effects, drugs such as angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are used in the clinic, although these do have side effects and can lead to excessive retention of potassium hyperkalaemia.
Control of plasma sodium and potassium concentrations, and the regulation of blood volume and pressure, are all hormonal mechanisms that are impaired by low angiotensin levels.
Absence of angiotensin can be associated with retention of potassium, loss of sodium, decreased fluid retention increased urine output and low blood pressure. About Contact Events News.
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