Regulation of Salt and Water Balance Part 2

Atrial Natriuretic Factor (ANF) • Atrial natriuretic factor (ANF) as its name implies promotes the excretion of sodium (Natrium in Latin) in the urine • It is synthesized, stored in membrane-bound granules, and secreted by exocytosis from cardiac atrial myocytes • A second natriuretic peptide originally isolated from pig brain, and therefore called brain natriuretic peptide (BNP), is also produced in the atria and to a greater extent in ventricles of the human heart Dr. M. Alzaharna (2018) 2

Atrial Natriuretic Factor (ANF) • The biological actions of both ANF and BNP are mediated by natriuretic peptide receptor. A (NPR-A), which forms dimers or tetramers in the membranes of target cells • ANF and BNF produce their biological effects by stimulating the formation of cyclic GMP, which may modify cellular functions through at least three mechanisms: Dr. M. Alzaharna (2018) 3

Atrial Natriuretic Factor (ANF) 1. Cyclic GMP binds to and activates cyclic GMPdependent protein kinase (PKG), which catalyzes the phosphorylation of key regulatory proteins 2. Cyclic GMP also binds to and regulates the activity of cyclic nucleotide phosphodiesterases, and may therefore lower cellular concentrations of cyclic AMP 3. Finally, cyclic GMP may bind directly to ion channel proteins and regulate their activity Dr. M. Alzaharna (2018) 4

Physiological actions • The physiological role of ANF is to protect against volume overload • Through its combined effects on the cardiovascular system, the kidneys, and the adrenal glands, it lowers mean arterial blood pressure and decreases the effective blood volume • Its physiological effects are essentially opposite to those of angiotensin II Dr. M. Alzaharna (2018) 5

Actions of Atrial Natriuretic Factor Dr. M. Alzaharna (2018) Direct and indirect actions of ANF on the kidney 6

Regulation of ANF Secretion • Under normal physiological circumstances expansion of vascular volume increases the rate of right atrial filling and hence atrial pressure • The principal stimulus for secretion of ANF is increased stretch of atrial muscle fibers produced by increased atrial pressure • Stretch-activated ion channels allow entry of cations and trigger ANF secretion • Increased secretion of ANF reduces the effective blood volume as described earlier, and when blood volume is restored to the normal range, secretion returns to basal levels Dr. M. Alzaharna (2018) 7

Integrated Compensatory Responses to Changes in Salt and Water Balance • The three hormones—ADH, angiotensin II, and aldosterone—collaborate to maintain or increase the effective volume of the blood plasma • In addition to reinforcing each other’s effects, each of these hormones acts at multiple sites to reinforce its own effects • Physiological responses to these hormones are countered by the natriuretic peptides, which act at many of the same target sites Dr. M. Alzaharna (2018) 8

Changes in Blood Volume • Volume changes can take several forms and may or may not be accompanied by changes in osmolality (sodium balance) Dr. M. Alzaharna (2018) 9

Hemorrhage Dr. M. Alzaharna (2018) 10

Dehydration Dr. M. Alzaharna (2018) 11

Salt loading and depletion Dr. M. Alzaharna (2018) 12