Angiotensin: From the Kidney to Coronavirus

Front Cover
Angiotensin
Molecular Mediators in Health  and Disease: How Cells Communicate Angiotensin: From the Kidney to Coronavirus
Copyright
Contents
List of contributors
Preface
	REFERENCES
1 - Regulation of sympathetic nerve activity by the central angiotensin system in heart failure
	1. Introduction
	2. Heart failure results in an increase in resting levels of sympathetic nerve activity
		2.1 Consequence of increased sympathetic nerve activity during heart failure
	3. Role of angiotensin II
		3.1 Circulating levels of angiotensin II in heart failure
		3.2 Role of central angiotensinergic mechanisms
		3.3 Blockade of central angiotensin type 1 receptor decreases SNA
		3.4 Central regions that respond to angiotensin II
			3.4.1 The role of the paraventricular nucleus of the hypothalamus in heart failure
			3.4.2 Actions of angiotensin II within the rostral ventral lateral medulla
			3.4.3 Actions of Ang II within the area postrema
	4. Actions of angiotensin II within the spinal cord
		4.1 AT1R within the spinal cord
		4.2 Regulation of sympathetic nerve activity by AT1R within the spinal cord
		4.3 Changes in spinal cord AT1R during heart failure
	5. Conclusions
	6. Future directions
	References
2 - The contribution of angiotensin peptides to cardiovascular neuroregulation in health and disease
	1. Introduction
	2. The overview of renin–angiotensin system organization: cooperation of central and systemic renin–angiotensin system
	3. Cooperation of the brain renin–angiotensin system with the autonomic nervous system: interactions with the sympathetic, par ...
	4. Role of the brain renin–angiotensin system in the regulation of water–electrolyte balance
		4.1 Regulation of sodium and water intake
		4.2 Kidney and gastrointestinal system
	5. Other effects of the brain renin–angiotension system affecting the cardiovascular regulation: role of renin–angiotension sy ...
		5.1 Stress and depression
		5.2 COVID-19
	6. Role of the brain renin–angiotensin system in cardiovascular regulation in hypertension
	7. Role of brain renin–angiotensin in cardiovascular regulation in heart failure
	8. Renin–angiotension system in diabetes mellitus and metabolic syndrome
	9. Renin–angiotensin system in pathogenesis and outcome of myocardial infarction
		9.1 Renin–angiotensin system and the atherosclerotic plaque
		9.2 Renin–angiotensin system in outcome of myocardial infarction
	10. Novel therapeutic perspectives of brain targeting renin–angiotensin system inhibitors in cardiovascular diseases
		10.1 ACE inhibitors
		10.2 Angiotensin receptor blockers
	11. Conclusions and perspectives
	References
3 - Renin–angiotensin system and inflammation
	1. Introduction
	2. The classic renin–angiotensin system axis
		2.1 Renin
			2.1.1 Renin role in inflammation
		2.2 Angiotensin-converting enzyme
			2.2.1 Angiotensin-converting enzyme role in inflammation
		2.3 Angiotensin II
			2.3.1 Angiotensin type 1 receptor
				2.3.1.1 Angiotensin II type 1 receptor role in inflammation
				2.3.1.1 Angiotensin II type 1 receptor role in inflammation
			2.3.2 Angiotensin type 2 receptors
				2.3.2.1 Angiotensin II type 2 receptors role in inflammation
				2.3.2.1 Angiotensin II type 2 receptors role in inflammation
	3. The counterregulatory renin–angiotensin system axis
		3.1 Angiotensin-converting enzyme 2
			3.1.1 ACE2 role in inflammation
		3.2 Angiotensin-(1–7)
		3.3 Mas receptor
			3.3.1 Angiotensin-(1–7) and Mas receptor role in inflammation
	4. Other renin–angiotensin system mediators
		4.1 Alamandine
		4.2 Ang-(1–9)
	5. Evidence in human diseases
	6. Future directions and perspectives
	References
4 - Targeting renin–angiotensin system: a strategy for drug development against neurological disorders
	1. Introduction
	2. Renin–angiotensin system in brain
	3. Drug development strategies targeting renin–angiotensin system
		3.1 MasR agonists
	4. ACE2 activators
	5. AT2R agonists
	6. ACE inhibitors
	7. AT1R blockers
	8. Renin inhibitors
	9. Conclusion
	References
5 - Pharmacology of angiotensin in renovascular diseases
	1. Introduction
	2. RAAS in the glomerulus and tubular region: physiological and pathological considerations
	3. Renovascular hypertension
		3.1 Pathophysiology of renovascular hypertension
		3.2 Role of angiotensin II in renovascular hypertension
		3.3 AT2 receptor activation in renovascular hypertension
	4. Atheromatous renovascular disease
		4.1 Pathophysiology of ARVD
		4.2 Angiotensin II in progression of ARVD
		4.3 Role of ACE-I/ARBs (ACE inhibitors/angiotensin receptor blockers) in ARVD
	5. Ischemic renovascular disease
		5.1 Pathophysiology
		5.2 Role of Angiotensin II in ischemia nephropathy
	6. Diabetic nephropathy
		6.1 Pathogenesis of diabetic nephropathy
		6.2 Role of angiotensin II, ACE inhibitors, and ARBs in diabetic nephropathy
	7. Conclusion
	8. Conflict of interest
	References
6 - The role of angiotensins in the pathophysiology of human pregnancy
	1. Introduction
	2. The renin–angiotensin system
	3. The circulating renin–angiotensin–aldosterone system in normal pregnancy
		3.1 Changes in components of the RAAS in human pregnancy
	4. The intrarenal RAS in pregnancy
	5. The intrauterine renin–angiotensin system: placenta, fetal membranes, and decidua
		5.1 RAS components in the placenta in normal pregnancy
			5.1.1 Effects of fetal sex, gestation, and labor on the expression of the placental RAS
		5.2 RAS components in the intrauterine membranes in normal pregnancy
			5.2.1 Effects of gestation and labor on the expression of the RAS in fetal membranes
		5.3 RAS components in the decidua in normal pregnancy
			5.3.1 Effects of fetal sex, gestation, and labor on the expression of the RAS in fetal membranes
	6. The RAS and hypertension in pregnancy
	7. The role of the RAS in regulating fetal growth
		7.1 Changes in the maternal circulating RAAS in pregnancies associated with FGR
		7.2 Changes in placental RAS expression in pregnancies associated with FGR
	8. The RAS in gestational diabetes
	9. Conclusions
	References
7 - Hematopoietic bone marrow renin-angiotensin system in health and disease
	1. Introduction
	2. Local bone marrow renin–angiotensin system in hematopoiesis
	3. Local bone marrow renin–angiotensin system in neoplastic hematopoiesis
	4. Local bone marrow renin–angiotensin system in atherosclerosis
	5. Local bone marrow renin–angiotensin system in hypertension
	6. Local bone marrow renin–angiotensin system and COVID-19 syndrome
	7. Conclusion and perspectives
	References
8 - Angiotensin II as a mediator of renal fibrogenesis
	1. Introduction
	2. The intrarenal renin–angiotensin system
		2.1 “Classical” actions of Ang II in the kidney
	3. The renal renin–angiotensin system: much more complex than previously thought
		3.1 Ang II and renal growth
		3.2 Ang II and renal inflammation
		3.3 Ang II and renal fibrosis
	4. Conclusion and future directions
	References
	Further reading
9 - Angiotensin and atherosclerotic vascular disease
	1. The global burden of the atherosclerotic vascular disease
	2. Endothelial dysfunction
	3. The renin–angiotensin system
	4. The role of angiotensin in the pathophysiology of atherosclerotic plaques
	5. Interaction between angiotensin and other mediators of the atherosclerotic process
	6. Angiotensin—clinical and therapeutical implications
	References
10 - ACE2 in pulmonary diseases
	1. Introduction
	2. ACE2 and pulmonary hypertension
	3. ACE2 and asthma
	4. ACE2 and pulmonary fibrosis
	5. ACE2 and lung cancer
	6. ACE2 and chronic obstructive pulmonary disease
	7. ACE2 and acute lung injury
	8. ACE2 and COVID-19
	9. Role of ACE2 in lung repair and regeneration
	References
11 - Renin–angiotensin–aldosterone system inhibitors. New and old approaches
	1. Introduction
	2. Why new drugs for hypertension
		2.1 Renin
			2.1.1 Angiotensinogen
			2.1.2 Blocking the activity of the ACE/Ang II/AT1-R
			2.1.3 Potentiating the opposing function of the ACE2/Ang-(1–7)/Mas-R axis
	3. Perspective
	References
12 - Aspects of the intracellular renin–angiotensin system
	1. Introduction
	2. Kidney
	3. Heart
	4. Brain
	5. Intracellular RAS ligands
	6. Summary
	References
13 - Interactions between the renin–angiotensin–aldosterone system and COVID-19: pharmacological interventions
	1. Introduction
		1.1 The physiology of the renin–angiotensin–aldosterone system
		1.2 The renin–angiotensin–aldosterone system and SARS-CoV-2
	2. Renin–angiotensin–aldosterone system therapeutic venues in the context of SARS-CoV-2 infection
		2.1 Direct renin inhibitor
		2.2 ACEIs/ARBs
		2.3 Aldosterone inhibitors (spironolactone)
		2.4 Beta-blockers
		2.5 Heparin
		2.6 Glucocorticoids
	3. Perspectives
	References
14 - Angiotensin II and its action within the brain during hypertension
	List of abbreviations
	1. Introduction
	2. Hypertension and angiotensin II
	3. Angiotensin II increases blood–brain barrier disruption in hypertension
	4. Angiotensin II, innate immune system, neuroinflammation, and hypertension
		4.1 AngII-induced microglia activation
		4.2 AngII and Toll-like receptors within the central nervous system
	5. Angiotensin II and bradykinin system
	6. Future perspectives
	7. List of words/terms
	References
15 - Morphological aspect of the angiotensin-converting enzyme 2
	1. Introduction
	2. Overview of the RAS/RAAS cascade
	3. ACE2 as a “functional receptor” during viral entry into cells
	4. Localization of ACE2 in various tissues
		4.1 Liver tissue
		4.2 Kidney tissue
		4.3 Pulmonary alveoli
		4.4 Other tissue in the digestive system
			4.4.1 Pancreas tissue
			4.4.2 Colon tissue
			4.4.3 Tongue mucosa and salivary gland
	5. Up- and downregulation of ACE2 and related diseases
		5.1 Two axes of RAAS cascade
		5.2 Expression of AT1, AT2, and MAS receptor
		5.3 Possible (down) regulation of the ACE2 after binding the SARS-CoV-2
	6. Summary
	References
	Further reading
16 - The renin-angiotensin system in the eye: implications on health and disease
	1. Introduction
	2. Human eye\'s anatomy and physiology
		2.1 Primary layers
		2.2 Visual processing
		2.3 Ocular barriers
		2.4 Ocular blood flow regulation
		2.5 Aqueous humor homeostasis and intraocular pressure
	3. Renin–angiotensin system
	4. Local renin–angiotensin system in the eye
	5. Eye diseases and the local renin–angiotensin system
		5.1 Glaucoma
		5.2 Diabetic retinopathy
		5.3 Age-related macular degeneration
		5.4 Retinopathy of prematurity
		5.5 Ocular SRA and COVID-19
	References
17 - Brain renin–angiotensin system in the injured brain: the role of astrocytes and microglia
	1. The renin–angiotensin system and the brain renin–angiotensin system
	2. Astrocytes are essential homeostatic cells in the CNS that respond to brain RAS activation
	3. Reactive astrogliosis is a generic response to brain injury
	4. Angiotensinogen expression in reactive astrocytes
	5. AT1R and AT2R role in glial cells: the dichotomy in neuroinflammation
	6. Angiotensin (1–7)/MasR pathway in the control of proinflammatory reactive gliosis
	7. Conclusions and future directions
	References
18 - Angiotensin and COVID-19
	1. Introduction
	2. SARS-CoV-2
		2.1 Spike (S) protein of SARS-CoV-2
	3. ACE2
		3.1 Interaction between S protein and ACE2
		3.2 Regulation of ACE2
	4. Genetic polymorphisms
	5. Effects of SARS-CoV-2 infection
		5.1 Respiratory system
		5.2 Cardiovascular system
		5.3 Nervous system
		5.4 Urinary system
		5.5 Gastrointestinal system
	6. Perspective and future therapeutical strategy
	7. Declaration
	References
19 - Transgenic animal models for the functional analysis of ACE2
	1. Introduction
		1.1 ACE2 knockout mice and rats
		1.2 Conditional ACE2 knockout
		1.3 ACE2 knock-in mutation in mice
		1.4 Cell type–specific overexpression of ACE2 in mice
		1.5 Human ACE2 overexpression in mouse brain
		1.6 Human ACE2 overexpression in mouse heart
		1.7 Human ACE2 overexpression in mouse podocytes
		1.8 Human ACE2 overexpression in rat vascular smooth muscle
		1.9 Humanized ACE2 expression in mouse/coronavirus infection models
	2. Conclusions and future directions
	References
20 - Role of angiotensin in different malignancies
	1. Introduction
	2. Renin–angiotensin–aldosterone system
		2.1 Primary components of RAS–angiotensin pathway
			2.1.1 Angiotensinogen
			2.1.2 Angiotensin-converting enzyme 2
			2.1.3 Angiotensin and its types
				2.1.3.1 Angiotensin I
				2.1.3.1 Angiotensin I
				2.1.3.2 Angiotensin II
				2.1.3.2 Angiotensin II
			2.1.4 Angiotensin (1–7) and Mas1
			2.1.5 Renin
			2.1.6 The bypass loops for RAS activation in cancer
		2.2 RAS components and cancer
	3. Clinical relevance of angiotensins in different cancers
		3.1 Cervical cancer
		3.2 Prostate cancer
		3.3 Esophageal cancers and Barrett\'s esophagus
		3.4 Ovarian cancer
		3.5 Hepatocellular carcinoma
		3.6 Breast cancer
		3.7 Pancreatic cancer
		3.8 Lung cancer
		3.9 Gastric cancer
		3.10 Colorectal cancer
	4. Angiotensin receptor inhibition and reprogramming of tumor microenvironment
	5. Inhibition of RAS components and impact on cancer progression
	6. Challenges associated with angiotensin inhibitors
	7. Perspectives
	References
21 - ACE2/angiotensin-(1–7)/mas receptor axis in the central nervous system: physiology and pathophysiology
	1. Introduction
	2. ACE2/Ang-(1–7)/mas receptor axis in central nervous system physiology
	3. ACE2/Ang-(1–7)/mas receptor axis in central nervous system pathophysiology
		3.1 ACE2/Ang-(1–7)/mas receptors role in neurodegenerative disorders
			3.1.1 Parkinson\'s disease
			3.1.2 Alzheimer\'s disease
		3.2 ACE2/Ang-(1–7)/mas receptors role in mood disorders
		3.3 ACE2/Ang-(1–7)/mas receptors role in cerebrovascular diseases
			3.3.1 Cerebrovascular ischemic disorders
			3.3.2 Cerebrovascular hemorrhagic disorders
			3.3.3 Traumatic brain injury
	4. Concluding remarks
	References
22 - The therapeutic potential of angiotensin-(1–7)
	1. Introduction
	2. Angiotensin-(1–7)/Mas1 receptor axis
	3. Ang-(1–7)/Mas1 axis—a target for cancer drug development
	4. Preclinical research
		4.1 In vitro studies
		4.2 Animal models
		4.3 Ang-(1–7)—combination therapy
	5. Clinical research
		5.1 Clinical trials in cancer patients administered Ang-(1–7)
		5.2 Ang-(1–7) with standard-of-care chemotherapy
	6. Future directions
		6.1 Limitations of Ang-(1–7) as a drug
		6.2 Analogs of Ang-(1–7) with anticancer properties
	7. Conclusions
	References
23 - Angiotensin and pain
	1. Introduction
		1.1 The renin–angiotensin system
		1.2 Basics on pain
		1.3 Brief introduction to the roles of angiotensin in the context of pain
	2. Role of angiotensin and its major receptors (and associated signaling molecules) in pain
		2.1 Angiotensin in nocifensive pain
		2.2 Angiotensin and neuropathic (pathological) pain
		2.3 Angiotensin and inflammatory pain
		2.4 Angiotensin and cancer pain
		2.5 Angiotensin and muscle pain
		2.6 Angiotensin and fibromyalgia
		2.7 Angiotensin and sickle cell–associated pain
	3. Outside the box: a link between RAS, thyroid hormones, and pain?
	4. COVID-19, RAS, thyroid status, and pain
	5. Concluding remarks
	References
	Further reading
24 - The renin-angiotensin system, emotional stress and anxiety
	1. Renin–angiotensin system and emotional stress: general aspects
		1.1 Emotional stress and anxiety disorders: need for new therapeutic strategies
		1.2 Contemporary renin–angiotensin system: far more complex than initially proposed
		1.3 The renin–angiotensin system: from vascular effects to behavioral modulation
	2. RAS components as therapeutical targets for stress-associated conditions: potential strategies
		2.1 Blockade of classical axis: ACE/angiotensin II/AT1 receptors
		2.2 Activation of ACE2/angiotensin-(1–7)/Mas receptor axis
	3. Clinical evidence: should doctors prescribe AT1 receptor blockers and ACE inhibitors for stress-associated conditions?
	4. Conclusions
	References
25 - Angiotensins in obesity: focus on white adipose tissue
	1. Introduction
	2. Ang II: main functions in WAT
		2.1 Lipid storage
		2.2 Adipogenesis
		2.3 Inflammation
		2.4 Glucose metabolism
		2.5 Browning
	3. Ang (1–7): main functions in WAT
		3.1 Lipid storage
		3.2 Adipogenesis
		3.3 Inflammation
		3.4 Glucose metabolism
		3.5 Browning
	4. Additional angiotensins
		4.1 Ang III or Ang (2–8)
		4.2 Ang IV or Ang (3–8)
		4.3 Alamandine
		4.4 Final remarks
	References
26 - Angiotensin in the gut: roles in inflammatory bowel disease
	1. Introduction
	2. The renin–angiotensin system
	3. Local renin–angiotensin system in the intestine
	4. The renin–angiotensin system and inflammatory bowel disease
	5. Perspectives
	References
27 - The renin–angiotensin system in gastrointestinal functions
	1. Introduction
	2. RAS and gut motility
		2.1 Upper gastrointestinal tract: esophagus, lower esophageal sphincter, and stomach
		2.2 Small intestine
		2.3 Large intestine
	3. RAS and epithelial functions
		3.1 Upper gastrointestinal tract: esophagus and stomach
		3.2 Small intestine
		3.3 Large intestine
	4. Summary and conclusions
	References
28 - Angiotensin in shock: experimental and clinical studies
	1. Background
	2. Experimental studies
		2.1 Sepsis
		2.2 Ovine model of sepsis
		2.3 Angiotensin II in early experimental sepsis
		2.4 Renal bioenergetics
		2.5 Intrarenal perfusion and oxygenation in sepsis
		2.6 Effects of Ang II on intrarenal perfusion and PO2 in established sepsis
	3. Clinical studies
		3.1 Angiotensin II, an emerging vasopressor for use in sepsis
		3.2 Ang II treatment for COVID-19
		3.3 Angiotensin II treatment for postoperative hypotension
		3.4 Safety of angiotensin II
		3.5 Cost-effectiveness
		3.6 Angiotensin I/II ratio and renin
		3.7 Future directions
	References
29 - Angiotensin II and astrocytes relevance in mental disorders
	1. Introduction
	2. Astrocytes in dopamine-related mental disorders
		2.1 Parkinson’s disease
		2.2 Major depression
		2.3 Schizophrenia
	3. AT1-R in dopamine imbalance: our first evidence
		3.1 Astrocytes in ketamine-induced dopamine–glutamate imbalance model
		3.2 Study of AT1-R involvement in long-lasting ketamine effects in the dorsal striatum
	4. Final considerations
	References
30 - Angiotensin II and polycystic kidney disease
	1. Introduction
	2. Evidence of RAS dysregulation in PKD
	3. Ang II cross-talk with cystogenic pathways
	4. The role of Ang II in abnormal water and salt handling in PKD
	5. The role of Ang II in extrarenal disease in PKD
	6. ACE inhibitors/ARBs in clinical trials
	7. Conclusion
	8. Disclosure
	References
31 - The role of angiotensin peptides in the brain during health and disease
	1. Introduction
		1.1 The formation of angiotensin peptides
		1.2 Angiotensin receptors
		1.3 Angiotensin and the regulation of neurovascular structure and function
	2. Angiotensin in the development of cognitive impairment
		2.1 Hypertension
		2.2 Stroke
	3. The role of angiotensin in the brain: contributions to memory, learning, and cognitive impairment
		3.1 Memory and learning
		3.2 Cognitive impairment and dementia
	4. Modulation of the RAAS as a therapy for cognitive impairment and dementia
		4.1 ACE inhibitors
		4.2 AT1R antagonists
		4.3 AT2R agonists
		4.4 The ACE2/angiotensin (1–7)/MasR axis
		4.5 Angiotensin IV and AT4R agonist
		4.6 Other components of the RAAS
	5. Conclusion
	References
Index
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