Nephrons

Cortisol-Cortisone Conversion. Under normal conditions, this equilibrium slightly favors the oxidized compound. Similarly, the conversion of corticosterone to 11-deoxycorticosterone is also mediated by the liP-hydroxysteroid dehydrogenase enzyme system and requites NAD(P) /NAD(P)H. This conversion is especially important both in the protection of the human fetus from excessive glucocorticoid exposure, and in the protection of distal nephron mineral ocorticoid receptors from glucocorticoid exposure (14). The impairment of this conversion is thought to result in hypertension associated with renal insufficiency (15). 

Potassium-Sparing Diuretics. Potassium-sparing diuretics act on the aldosterone-sensitive portion of cortical collecting tubules, and partially in the distal convoluted tubules of the nephron. The commonly used potassium-sparing diuretics are triamterene, amiloride, and spironolactone (Table 3). Spironolactone is a competitive aldosterone receptor antagonist, whereas triamterene and amiloride are not (44,45). 

Logically, ADH receptor antagonists, and ADH synthesis and release inhibitors can be effective aquaretics. ADH, 8-arginine vasopressin [113-79-17, is synthesized in the hypothalamus of the brain, and is transported through the supraopticohypophyseal tract to the posterior pituitary where it is stored. Upon sensing an increase of plasma osmolaUty by brain osmoreceptors or a decrease of blood volume or blood pressure detected by the baroreceptors and volume receptors, ADH is released into the blood circulation it activates vasopressin receptors in blood vessels to raise blood pressure, and vasopressin V2 receptors of the nephrons of the kidney to retain water and electrolytes to expand the blood volume. 

ENaC is located in the apical membrane of polarized epithelial cells where it mediates Na+ transport across tight epithelia [3], The most important tight epithelia expressing ENaC include the distal nephron of the kidney, the respiratory epithelium, and the distal colon. The basic function of ENaC in polarized epithelial cells is to allow vectorial transcellular transport of Na+ ions. This transepithelial Na+ transport through a cell involves... 

Epithelial Na Channel. Figure 1 Transepithelial ion transport in a principal cell of the aldosterone-sensitive distal nephron (ASDN). 

In the aldosterone-sensitive distal nephron (ASDN), ENaC-mediated Na+ absorption under the control of aldosterone is critical to balance urinary Na+ excretion with the daily intake. ENaC allows Na+ entry from the tubule lumen at the apical membrane, and the Na+/K.+ ATPase extrudes Na+ at the basolateral side. The Na+ absorption in the distal nephron is coupled to K+ secretion via K+ channels (ROMK2) located at the apical membrane. 

Til tee successive tubule portions contribute to the ASDN the late portion of the distal convoluted tubule, the connecting tubule, and the collecting duct. The recent observation that collecting duct-specific inactivation of aENaC in the mouse kidney does not impair sodium and potassium balance, suggests that the more proximal nephron segments (late distal convoluted tubule, connecting tubule) are mainly important for-achieving sodium and potassium balance. 

Since the distal nephron reabsorbs under physiological conditions less than 10% of the filtered load of... 

The macula densa is a dense aggregation of cells in the distal tubule of nephrons facing the glomerular tuft of capillaries. These cells sense the salt content of the distal tubular fluid and adjust glomerular perfusion and renin secretion accordingly. 

NKCC is a heavily glycosylated protein with 12 putative membrane-spanning regions. Thirty percent of the sodium that is filtered by renal glomeruli is reabsorbed by Na-K-2C1 cotransport in the ascending limb of Henle in the nephron. Na-K-2C1 cotransport is a target of all loop diuretics. 

Urodilatin is a peptide similar to atrial natriuretic peptide, which is produced in the distal tubule of the kidney and promotes sodium excretion and diuresis by acting on receptors localized on the luminal site of the collecting duct of the nephron. 

The Summary Drug Table Diuretics lists examples of die different types of diuretic drugp. Most diuretics act on die tubules of die kidney nephron (Pig. 46-1), the functional unit of the kidney. Each kidney contains about one million nephrons, which filter die bloodstream to remove waste products. During diis process,... 

Figure 46-1. The nephron is the functional unit of the kidney. Note the various tubules, the site of most diuretic activity. The loop of Henle is the site of action for the loop diuretics. Thiazide diuretics ad at the ascending portion of the loop of Henle and the distal tube of the nephron.

Thiazides and related diuretics inhibit the reabsorption of sodium and chloride ions in the ascending portion of the loop of Henle and the early distal tubule of the nephron. This action results in the excretion of sodium, chloride, and water. 

Northern blot analysis revealed that expression of NHE-1 is tissue-specific with highest transcript abundance in stomach and minimal levels in liver and skeletal muscle. Moreover, there is physiological evidence that certain segments of the nephron lack a basolateral Na /H" exchanger [76]. Using RT-PCR, Krapf and Solioz [77] observed that NHE-1 transcripts are not detectable in SI and S2 segments of superficial nephrons. 

The physiological role of the ICOR is not clear and may be heterogeneous in the various tissues. In the thick ascending limb of the loop of Henle this channel appears to serve as the exit for CP at the basal cell pole [16,65,66], This conductive mechanism, therefore, is required for the reabsorption of Na and CP by this segment of the nephron [16]. In the rectal gland of Squalus acanthias a very similar channel is utilized for Na" and CP secretion. In these latter cells the CP-channel is present in the luminal membrane and is controlled by cytosolic cAMP [15,56,71]. It has been claimed that this kind of channel is also responsible for the secretion of CP in the colonic crypt cell, in colonic carcinoma cells and in respiratory epithelial cells [17,19,20,22]. Recent data have cast some doubt on this concept ... 

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