Autoregulation: mediators and renin–angiotensin system in diseases and treatments

Abstract

Abstract Background Hemodynamic regulation is a substantial part of the physiological integrity of the human body. It is based on the delivery of proper blood perfusion to every organ. Five primary vasoactive substances are nearly located throughout the human body, either released from the endothelium, prostanoids, nitric oxide (NO), and endothelin-1 (ET-1); or considered as hormones, bradykinin (BK) and natriuretic peptides (NPs). Main body The circulating mediators are in synchronization with the renin–angiotensin system (RAS) during the pathogenesis of the main vital organs, heart, kidney, lung, liver, and brain. The RAS system has been an extensive therapeutic approach for cardiovascular and renal diseases for decades, but more recently became a crucial regulator of hemodynamics in other organs after the actions of its components were detected in other organs. All the mentioned disorders here begin with the initiation of abnormal imbalance between vasoactive mediators which causes vascular dysfunction and histopathological situations that may induce oxidative stress which exaggerates the disorder if there is no clinical intervention. Conclusion We will review the currently identified signaling pathways and the possible relationships between those compounds elucidating how they interfere with serious diseases including cardiovascular diseases (CVDs), chronic kidney disease (CKD), pulmonary arterial hypertension (PAH), portal hypertension (PHT), and Alzheimer's disease (AD). Thus, this updated review summarizes years of work that aims to define the contribution of each mediator in both normal and pathological states, besides the drugs based on their activity and their places in either preclinical or clinical trials.

Keywords

• Prostacyclin (PGI2)
• Cyclooxygenase-2
• Neprilysin
• N-terminal prohormone of brain natriuretic peptide
• Angiotensin (1–7)
• Angiotensin-converting enzyme inhibitors