Angiotensin ii
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Angiotensin II: Mechanisms, Effects, and Clinical Implications
Introduction to Angiotensin II
Angiotensin II (Ang II) is a critical hormone in the renin-angiotensin-aldosterone system (RAAS), playing a significant role in regulating blood pressure, fluid balance, and electrolyte homeostasis. It exerts its effects through two primary receptor subtypes, AT1 and AT2, which mediate various physiological and pathophysiological processes .
Angiotensin II and Cardiovascular Pathophysiology
Cardiac Hypertrophy and Heart Failure
Ang II is a key player in the progression of myocardial hypertrophy to heart failure. It influences cardiomyocytes through different isoforms of angiotensin-converting enzyme (ACE) and interacts with other hormones and cytokines, such as transforming growth factor (TGF)-beta1 and interleukin (IL)-6, to mediate its effects. The hormone's action is modulated by nitric oxide (NO)/cGMP-dependent cross-talk, which further complicates its role in cardiac pathology.
Vascular Remodeling and Hypertension
The AT1 receptor is central to Ang II's role in causing hypertension and cardiovascular remodeling. It activates various signal transduction pathways, including mitogen-activated protein kinase (MAPK) cascades and tyrosine kinases, leading to cellular growth and phenotypic changes in vascular smooth muscle cells (VSMCs) . These pathways are not isolated but engage in cross-talk, resulting in complex and multifaceted responses.
Angiotensin II in Renal Diseases
Ang II is implicated in the pathophysiology of renal diseases, particularly through its effects on glomerular mesangial cells. It induces the synthesis of extracellular matrix proteins by upregulating TGF-beta, contributing to glomerulosclerosis. This mechanism highlights the hormone's role in promoting renal fibrosis and chronic kidney disease .
Angiotensin II and Atherosclerosis
Ang II is a significant risk factor for atherosclerosis. It stimulates macrophage cholesterol biosynthesis via the AT1 receptor, leading to increased cholesterol accumulation and foam cell formation, which are critical steps in atherogenesis. This process is attenuated by ACE inhibitors and AT1 receptor antagonists, underscoring the therapeutic potential of targeting Ang II in atherosclerotic disease.
Therapeutic Implications and Safety Profile
Angiotensin II Receptor Blockers (ARBs) and ACE Inhibitors
ARBs and ACE inhibitors are widely used to mitigate the effects of Ang II in hypertension, heart failure, and renal diseases. These therapies block the production or action of Ang II, thereby reducing its pathological effects on the cardiovascular and renal systems .
Safety of Intravenous Angiotensin II
A systematic review of intravenous Ang II administration in humans indicates that while adverse events are infrequent, they can include exacerbation of left ventricular failure and bronchoconstriction. The overall safety profile supports its use in clinical settings, although careful monitoring is necessary.
Conclusion
Angiotensin II is a pivotal hormone in cardiovascular and renal physiology and pathology. Its complex signaling mechanisms and interactions with other molecular pathways make it a critical target for therapeutic intervention. Understanding these mechanisms can lead to more effective treatments for hypertension, heart failure, atherosclerosis, and renal diseases.
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