Year: 2018
Type: article
Abstract: Since the discovery of renin, 120 years ago, the renin-angiotensin system (RAS) has expanded considerably. First characterized as a hormone, renin is now known as the rate-limiting enzyme for production of angiotensin peptides. The discovery of angiotensin-converting enzyme (ACE) generated the concept of a cascade involving angiotensinogen (renin substrate), angiotensin I, and angiotensin II, the active peptide of the system. Subsequently three additional active angiotensin peptides have been identified; angiotensin III, angiotensin IV, and angiotensin 1-7. There are four angiotensin receptors; AT1 angiotensin II receptor subtype, AT2 angiotensin II receptor subtype, AT4 angiotensin receptor (also known as insulin-regulated aminopeptidase) and mas (the receptor for angiotensin 1-7). The initial observation that the RAS regulates blood pressure is still viewed as its primary role, however, it does so by many mechanisms; it promotes thirst and salt (NaCl) appetite, it activates the sympathetic nervous system at specific brain loci as well as sympathetic nerve terminals to increase blood pressure, it stimulates release of the vasoconstrictor and water retaining hormone vasopressin (antidiuretic hormone) release from the posterior pituitary, it stimulates synthesis and release of aldosterone from the adrenal to promote renal sodium reabsorption, and it acts directly on renal tubules to increase sodium reabsorption. In addition to regulating blood pressure and fluid and electrolyte homeostasis, the RAS is now recognized as having many additional functions: regulation of cell growth, including promotion and inhibition of tumor cell growth and fibrosis, activation of immune cells, promotion of inflammation, exacerbation of atherosclerosis, stimulation and inhibition of prolactin release, promotion of stress responses through stimulation of hypothalamic corticotropin releasing hormone release, alteration of cognitive function, participation in neurodegenerative disease processes, and participation in reproductive function. Surprisingly, the AT2 angiotensin II receptor subtype and the mas receptor for angiotensin 1-7 exert effects that counter the pathophysiological effects of AT1 receptor activation. In view of the pathophysiological potential of the RAS not only for the cardiovascular system, but many other organ systems, there is a continuing need for development and refinement of drugs that counter the adverse effects of the RAS and promote the beneficial effects of the RAS.
Language: English
Subfield: Cardiology and Cardiovascular Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W3084141589