3. Delivery of NaCl to the macula densa. Delivery of NaCl to the macula densa regulates GFR by a process termed tubuloglomerular feedback (see ). In addition the macula densa plays a role in renin secretion. When NaCl delivery to the macula densa is decreased, renin secretion is enhanced. Conversely, an increase in NaCl delivery inhibits renin secretion. It is likely that macula densa–mediated renin secretion helps maintain systemic arterial pressure under conditions of a reduced vascular volume. For example, when vascular volume is reduced, perfusion of body tissues (including the kidneys) decreases. This in turn decreases GFR and the filtered amount of NaCl. The reduced delivery of NaCl to the macula densa stimulates renin secretion, which acts through angiotensin II (a potent vasoconstrictor) to increase blood pressure and thereby maintain tissue perfusion.
Although many tissues express renin (e.g., brain, heart, adrenal gland), juxtaglomerular (JG) cells are the primary source of circulating renin; they are located in the afferent arterioles of the kidneys. Renin secretion is stimulated by a decrease in intracellular [Ca++], a response opposite that of most secretory cells, where secretion is stimulated by an increase in intracellular [Ca++]. Renin secretion is also stimulated by an increase in intracellular cAMP levels. Conversely, anything that increases intracellular [Ca++] will inhibit renin secretion. Renin secretion is also inhibited by increases in intracellular cyclic guanosine monophosphate (cGMP).
Stretch of the afferent arteriole, angiotensin-II, and endothelin increase intracellular [Ca++] and thus inhibit renin secretion by JG cells. The stimulatory effect of sympathetic nerve activity on renin secretion is mediated by norepinephrine, which increases intracellular cAMP (via β-adrenergic receptors). Prostaglandin E2 also increases JG cell cAMP levels and therefore stimulates renin secretion. Natriuretic peptides and nitric oxide (NO) inhibit renin secretion by increasing intracellular cGMP.
Control of renin secretion by the macula densa is complex and appears to involve several paracrine factors, including ATP, adenosine, and prostaglandin E2 (see
Fig. 35.10 summarizes the essential components of the renin-angiotensin-aldosterone system (RAAS). Renin alone does not have a physiological function; it functions solely as a proteolytic enzyme. Its substrate is a circulating protein, angiotensinogen, which is produced by the liver. Angiotensinogen is cleaved by renin to yield a 10–amino acid peptide, angiotensin I. Angiotensin I also has no known physiological function, and it is cleaved to an 8–amino acid peptide, angiotensin II, by angiotensin-converting enzyme (ACE) found on the surface of vascular endothelial cells. Lung and renal endothelial cells are important sites for the conversion of angiotensin I to angiotensin II. ACE also • Fig. 35.10 Schematic representation of the essential components of the renin-angiotensin-aldosterone system (RAAS). Activation of this system results in a decrease in excretion of Na+ and water by the kidneys. NOTE: Angiotensin I is converted to angiotensin II by an angiotensin-converting enzyme that is present on all vascular endothelial cells. As shown, the endothelial cells within the lungs play a significant role in this conversion process. See text for details.
degrades bradykinin, a potent vasodilator. Angiotensin II has several important physiological functions: 1.
stimulation of aldosterone secretion by the adrenal cortex 2.
arteriolar vasoconstriction, which increases blood pressure 3.