Angiotensin action
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Angiotensin Action: A Comprehensive Overview
Angiotensin II and Cardiovascular Health
Role in Myocardial Hypertrophy and Heart Failure
Angiotensin II (Ang II) is a critical hormone in the progression of myocardial hypertrophy to heart failure. It exerts its effects through the angiotensin-converting enzyme (ACE) and Ang II receptors, which are differentially expressed in cardiomyocytes from neonatal, adult, and failing hearts. The intracellular effects of Ang II are mediated by nitric oxide (NO)/cGMP-dependent cross-talk and the release of autocrine factors such as transforming growth factor (TGF)-beta1 and interleukin (IL)-6. Additionally, Ang II interacts with systemic networks including aldosterone, parathyroid hormone, and adrenomedullin, which can modify its primary effects.
Molecular and Cellular Mechanisms
Ang II plays a central role in the etiology of hypertension and the pathophysiology of cardiovascular and renal diseases. It causes cellular phenotypic changes, regulates gene expression of various bioactive substances, and activates multiple intracellular signaling cascades in cardiac myocytes, fibroblasts, vascular endothelial and smooth muscle cells, and renal mesangial cells. These actions contribute to cardiac hypertrophy, heart failure, vascular thickening, atherosclerosis, and glomerulosclerosis.
Angiotensin II in Renal Function
Vasoconstrictor Action and Beyond
Ang II is well-known for its potent vasoconstrictor action in the renal circulation. However, it also has several other biological actions that have been extensively studied, revealing its multifaceted role in renal physiology and pathology.
Counterregulatory Actions of Angiotensin-(1-7)
Antihypertensive and Vasodilatory Effects
Angiotensin-(1-7) (Ang-(1-7)) is a bioactive component of the renin-angiotensin system that opposes the actions of Ang II. It exhibits depressor, vasodilator, and antihypertensive actions, which are more apparent in hypertensive conditions. These effects are mediated through the stimulation of prostaglandins and nitric oxide, explaining the effective antihypertensive action of ACE inhibitors.
Broader Physiological and Pathophysiological Roles
Ang-(1-7) also has a broad range of effects beyond cardiovascular and renal actions. It regulates different signaling pathways and involves downstream effectors such as NO, FOXO1, and COX-2. Through these mechanisms, Ang-(1-7) can improve pathological conditions including fibrosis and inflammation in various organs, enhance metabolism, and provide cerebroprotection against ischemic stroke. It also has potential anti-cancer properties by inhibiting cell proliferation and angiogenesis.
Angiotensin Receptors: Distribution and Function
AT1 and AT2 Receptors
The actions of Ang II are mediated by at least two receptor subtypes, AT1 and AT2. The AT1 receptor is responsible for most of the well-described actions of Ang II, such as vasoconstriction and cellular growth. In contrast, the AT2 receptor may play a role in mediating anti-proliferation, cellular differentiation, apoptosis, and vasodilation.
Angiotensin-(1-9) and Cardiac Fibrosis
Angiotensin-(1-9) is another peptide in the renin-angiotensin system that has been shown to block cardiomyocyte hypertrophy and reduce cardiac fibrosis via the AT2 receptor. It also improves basal NO bioavailability, suggesting a protective role in cardiovascular health.
Conclusion
Angiotensin II is a multifaceted hormone with significant roles in cardiovascular and renal health. Its actions are mediated through complex interactions with various receptors and signaling pathways. Counterregulatory peptides like Ang-(1-7) and Ang-(1-9) offer promising therapeutic avenues by opposing the detrimental effects of Ang II. Understanding these mechanisms provides valuable insights into potential treatments for hypertension, heart failure, and other related conditions.
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