70 Extrinsic control of GFR
Learning Objectives
After reading this section, you should be able to-
- For the renin-angiotensin system (RAS), describe the factors that initiate renin release, the pathway from angiotensinogen to angiotensin II (ANGII), and the effects of ANGII on various tissues.
- Describe the signals that cause release of aldosterone from the adrenal cortex and the effect of aldosterone on the nephron, including the tubule segment involved and the transport mechanisms that are altered by aldosterone.
- Describe the effect of vasopressin (ADH, antidiuretic hormone) on the nephron and on the final concentration of urine.
- Describe the factors that cause release of natriuretic peptide hormones, their sites of synthesis, and their effects on the nephron.
The kidneys are innervated by the sympathetic neurons of the autonomic nervous system via the celiac plexus and splanchnic nerves. Reduction of sympathetic stimulation results in vasodilation and increased blood flow through the kidneys during resting conditions. When the frequency of action potentials increases, the arteriolar smooth muscle constricts (vasoconstriction), resulting in diminished glomerular flow, so less filtration occurs. Under conditions of stress, sympathetic nervous activity increases, resulting in the direct vasoconstriction of afferent arterioles (norepinephrine effect) as well as stimulation of the adrenal medulla. The adrenal medulla, in turn, produces a generalized vasoconstriction through the release of epinephrine. This includes vasoconstriction of the afferent arterioles, further reducing the volume of blood flowing through the kidneys. This process redirects blood to other organs with more immediate needs. Under severe stress, such as significant blood loss, the sympathetic nervous system kicks into high gear to keep the blood routed to essential organs and keep the body alive. The strong vasoconstriction required to maintain systemic blood pressure under these severe conditions significantly reduces blood flow to the kidneys and can be damaging to the kidney tissues. If blood pressure falls, the sympathetic nerves will also stimulate the release of renin which we will discuss next.
Renin–Angiotensin–Aldosterone Mechanism
Recall that renin is an enzyme that is produced by the granular cells of the afferent arteriole at the JGA. It enzymatically converts angiotensinogen (made by the liver, freely circulating) into angiotensin I. Its release is stimulated by paracrine signals from the JGA in response to decreased extracellular fluid volume.
Angiotensin-converting enzyme (ACE) enzymatically converts inactive angiotensin I into active angiotensin II. ACE is not a hormone but it is functionally important in regulating systemic blood pressure and kidney function. It is produced in the lungs but binds to the surfaces of endothelial cells in the afferent arterioles and glomerulus. ACE is important in increasing blood pressure and this is why people with high blood pressure are sometimes prescribed ACE inhibitors to lower their blood pressure.
Angiotensin II is a potent vasoconstrictor that plays an immediate role in the regulation of blood pressure. It acts systemically to cause vasoconstriction as well as constriction of both the afferent and efferent arterioles of the glomerulus. Under the influence of Angiotensin II, the efferent arteriole constricts more strongly than the afferent arteriole, increasing GFR. In instances of blood loss or dehydration, Angiotensin II reduces both GFR and renal blood flow, thereby limiting fluid loss and preserving blood volume. Its release is usually stimulated by decreases in blood pressure, and so the preservation of adequate blood pressure is its primary role.
Adapted from Anatomy & Physiology by Lindsay M. Biga et al, shared under a Creative Commons Attribution-ShareAlike 4.0 International License, chapter 25