The Renin-Angiotensin System

The renin-angiotensin system (RAS) is an endocrine system that affects blood volume and blood pressure. The active player in the RAS is the final product of a cascade of events: angiotensin II. Angiotensin II binds to receptors on various cells involved in the control of blood volume (directly or indirectly via the kidney) and blood pressure (via effects on blood vessels and sympathetic nerves that innervate them). The RAS is triggered by low perfusion of the kidney, detected by cells surrounding the glomeruli – the juxtaglomerular apparatus, most importantly the macula densa.

renin angiotensin

Figure 1: Figure 1: ❶ Angiotensinogen is constitutively secreted by the liver as a protein (453 amino acids). Only the last 12 amino acids account for its biological activity in the RAS. ❷ In response to decreased perfusion pressure, renin is secreted by the juxtaglomerular cells in the kidney. Renin is a peptidase that removes the decapeptide (10 amino acids) angiotensin I from angiotensin protein. ❸ Angiotensin I is converted to Angiotensin II by angiotensin converting enzyme (ACE; another peptidase) located on pulmonary endothelial cells. This is an ideal location for a ACE (and other enzymes) since the entire cardiac output is pumped through the lung. Hence most of the angiotensin in venous blood is rapidly converted to angiotensin II. ❹ Angiotensin II has a variety of biological effects which act to increase blood volume and blood pressure. ❺ Once blood pressure is restored, the juxtaglomerular apparatus stops producing renin.

Effects of Angiotensin II

There are several subtypes of angiotensinII receptor, but only the AT1 receptor mediates the textbook effect of angiotensin II on cells of the cardiovascular, renal and endocrine systems. These effects all serve to increase blood volume and/or blood pressure:

  • Direct contraction of vascular smooth muscle
  • Increased sympathetic neurotransmitter release leading to increased vascular contraction
  • Release of aldosterone by the adrenal gland
  • Release of antidiuretic hormone (ADH) by the pituitary gland leading to increased water retention by the kidney

Drugs and the RAS

Several classes of drugs can interfere with the RAS and are used clinically to lower blood pressure. These include

  • ACE inhibitors: prevent conversion of angiotensin I to angiotensin II. E.g. Captopril
  • AT1 receptor blockers prevent angiotensin II from having effects. E.g. Losartan
  • Renin inhibitors. A newer class that prevent angiotensin I production. E.g. Aliskiren

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