The Renin-Angiotensin System
Austin E. Doyle, Frederick A. O. Mendelsohn, Trefor O. Morgan in Pharmacological and Therapeutic Aspects of Hypertension, 2020
This chapter reviews some of the evidence on the role of the renin-angiotensin system in hypertension as a background to the use of agents which block the action of the system. Emphasis has been placed on recent advances and topics of current or potential pharmacological importance. The biological activity of the renin-angiotensin system results from a series of specific enzymatic cleavages of polypeptide precursors leading to the generation of angiotensin II and related peptides. The section on the enzyme, renin, includes recent reports on purification of the enzyme since increased knowledge of the enzyme could lead to advances in modifying its action. Angiotensin II has been traditionally regarded as the biologically active end-product of the renin-angiotensin system. Inactive renin measured by acid activation comprised approximately 60 to 80% of total circulating renin in man and was also secreted by a kidney with a stenosed renal artery.
The renin-angiotensin-aldosterone system
Ben Greenstein in Rapid Revision in Endocrinology, 2017
This chapter examines some main components of the renin-angiotensin-aldosterone (RAA) system, their sources, properties, actions and termination of action. It presents some examples of drugs developed through knowledge of the RAA, and their uses. The RAA system is an endocrine hormone system important in the regulation of blood fluid volume and systemic blood pressure. Renin is an endocrine enzyme hormone secreted by the juxtaglomerular apparatus of the kidney; renin is released in response to a fall in blood pressure or an abnormal rise in blood osmolality; renin catalyses the release in blood of angiotensin. Angiotensin II constricts efferent glomerular arterioles preferentially, thus ensuring that the glomerulus continues to be adequately perfused in order to maintain the glomerular filtration rate. Constriction of afferent arterioles feeding capillary beds results in increased arteriolar resistance, which causes a rise in blood pressure.
◾ Delivery Methods for Radioenhancing Drugs
Shirley Lehnert in Radiosensitizers and Radiochemotherapy in the Treatment of Cancer, 2015
Nanoparticles are usually considered to be particles that are less than 100 nm in diameter. e interest surrounding these particles for drug delivery in the treatment of cancer and other diseases is largely related to the enhanced permeability and retention (EPR) eect. is is the property by which certain sizes of molecules (typically liposomes, nanoparticles, and macromolecular drugs) tend to accumulate in tumor tissue much more than they do in normal tissues. e explanation for this is that the newly formed tumor vessels are usually abnormal in form and architecture. ey consist of poorly aligned defective endothelial cells with wide fenestrations, lacking a smooth muscle layer, or innervation with a wider lumen, and impaired functional receptors for angiotensin II. Furthermore, tumor tissues usually lack eective lymphatic drainage.
Differential Regulation of Angiotensin Peptides in Plasma and Kidney: Effects of Adrenalectomy and Estrogen Treatment
Published in Clinical and Experimental Hypertension, 1997
Eight angiotensin peptides [angiotensin-(1–7), angiotensin II, angiotensin-(1–9), angiotensin I, angiotensin-(2–7), angiotensin-(2–8), angiotensin-(2–9), and angiotensin-(2–10)] were measured in plasma and kidney of adrenalectomized rats and estrogen-treated rats. In comparison with sham-operated rats, adrenalectomy increased plasma renin levels by 50-fold and reduced plasma angiotensinogen levels by 67%. Adrenalectomy increased plasma angiotensin peptide levels by 9- to 30-fold, but the increases in renal angiotensin peptide levels were much less than those seen for plasma. In comparison with vehicle-treated rats, estrogen treatment increased plasma angiotensinogen levels by 3-fold and reduced plasma renin levels by 41%. Estrogen treatment decreased plasma angiotensin peptide levels, whereas renal angiotensin peptide levels increased by as much as 2- to 3-fold. These results confirm the differential regulation of angiotensin peptide levels in plasma and kidney, and provide further support for the essential role of angiotensinogen in modulating plasma and tissue angiotensin peptide levels.
Hypertension regulating angiotensin peptides in the pathobiology of cardiovascular disease
Published in Clinical and Experimental Hypertension, 2018
Misbah Hussain, Fazli Rabbi Awan
ABSTRACT Renin angiotensin system (RAS) is an endogenous hormone system involved in the control of blood pressure and fluid volume. Dysregulation of RAS has a pathological role in causing cardiovascular diseases through hypertension. Among several key components of RAS, angiotensin peptides, varying in amino acid length and biological function, have important roles in preventing or promoting hypertension, cardiovascular diseases, stroke, vascular remodeling etc. These peptides are generated by the metabolism of inactive angiotensinogen or its derived peptides by hydrolyzing action of certain enzymes. Angiotensin II, angiotensin (1–12), angiotensin A and angiotensin III bind primarily to angiotensin II type 1 receptor and cause vasoconstriction, accumulation of inflammatory markers to sub-endothelial region of blood vessels and activate smooth muscle cell proliferation. Moreover, when bound to angiotensin II type 2 receptor, angiotensin II works as cardio-protective peptide and halt pathological cell signals. Other peptides like angiotensin (1–9), angiotensin (1–7), alamandine and angiotensin IV also help in protecting from cardiovascular diseases by binding to their respective receptors.
Local Generation of Angiotensin in the Kidney and in Tissue Culture
Published in Clinical and Experimental Hypertension. Part A: Theory and Practice, 1983
T. Inagami, T. Okamura, D. Clemens, M. R. Celio, K. Naruse, M. Naruse
The renin-angiotensin system is an exception among the various peptide hormone producing mechanisms in that it is an extracellular system. It was not clear whether renin in tissues other than kidney participates in the extracellular system or an intracellular mechanism. We examined the possibility of intracellular formation of angiotensin II in these tissues by using cloned, renin containing cells in culture as models. Neuroblastoma cells, pheochromocytoma cells, adrenal cortical cells and juxtaglomerular cells were shown to contain renin, angiotensin I and angiotensin II. Presence of angiotensin I converting enzyme was also demonstrated in some cell lines examined. Even juxtaglomerular cells in the intact kidney were shown to contain angiotensin I and angiotensin II by immuno-histochemical technique. These findings indicate an intracellular mechanism of angiotensin II formation in various tissues and suggest that angiotensin II may have local paracrine functions.
Related Knowledge Centers
- Kidney
- Aldosterone
- Vasoconstriction
- Blood Pressure
- Angiotensin Receptor
- Renin–Angiotensin System
- Peptide Hormone