Significance of the Renin-Angiotensin System in Clinical Conditions

Abstract

The renin-angiotensin system, in both its circulating and local tissue roles, is intertwined with multiple other regulatory and signalling mechanisms in various tissues and organ systems. It plays a central role in the normal regulation of arterial blood pressure and in the development of hypertension, which is an immense global public health burden and a crucial modifiable risk factor in the development of cardiovascular diseases. The renin-angiotensin system plays also important roles in a range of other clinical conditions such as heart failure, kidney failure, diabetes mellitus and others. Therapeutic interventions within the renin-angiotensin system include the use of medications such as angiotensin-converting enzyme inhibitors and angiotensin receptor antagonists, which are well established and have been invaluable as clinically effective tools during many years of practical use. Additionally, numerous other therapeutic approaches targeting components of the renin-angiotensin system have been developed or are currently in development. This chapter will discuss details of the roles of this system in the most relevant clinical conditions.

Endothelial senescence in vascular diseases: current understanding and future opportunities in senotherapeutics

“…The altered RAS can be identified by increased angiotensinconverting enzyme 1 (ACE1), angiotensin II (Ang II), and angiotensin II type-1 receptor (AT-1), which have been shown to induce fibrosis, inflammation, and oxidative stress in aged mouse thoracic aorta 42 . In conjunction with increased endothelin-1 43 , a vasoconstrictor peptide produced by ECs 44,45 , the altered RAS exerts vasoconstrictive pressure on the vasculature 46 .…”

Hormonal Regulation of Renal Fibrosis

“…One of the most promising strategies for the treatment of kidney fibrosis is the correction of RAAS function. The regulation of this system realizes through the use of renin inhibitors, AT1 antagonists, AT2 agonists, ACE1 and chymase inhibitors (an enzyme involved in the alternative Ang II synthesis pathway), as well as ACE2 stimulators [ 145 , 146 ]. Despite the significant antifibrotic effects of the aforementioned substances in vivo and in vitro, the use of AT1 and ACE1 blockers alone did not sufficiently suppress CKD progression, in contrast to their combination.…”

“…Substance C21, a synthetic AT2 agonist, showed antifibrotic and antithrombotic effects in animal models [ 145 ] and started to be introduced into clinical practice. C21 suppressed the proinflammatory response, the release of TNF-α and interleukine-6 during the acute phase of renal ischemia-reperfusion and stimulated anti-inflammatory responses in the delayed post-ischemic period due to the activation of T-regulatory cells and the release of interleukine-10 [ 60 , 145 ].…”

A Bioelectromagnetic Proposal Approaching the Complex Challenges of COVID-19

“…The impoverished ACE2 availability with the expansion of the infection or the too intense ACEI/ARB activates the kallikrein-quinine system (KKS), counteracting the RAS [142], i.e. that is, any decrease or predominance causes the opposite corrective change in the paired system [143].…”