 FOLDER 20.4 Clinical Correlation: Renin–Angiotensin– Aldosterone System (RAAS) and Hypertension Angiotensin II is also a potent vasoconstrictor that has a regulatory role in the control of renal and systemic vascu lar resistance.
The juxtaglomerular apparatus functions not only as an endocrine organ that secretes renin but also as a sensor of blood volume and tubular fluid composition. The cells of the macula densa monitor the Na concentration in the tubular fluid and regulate both the glomerular filtration rate and the release of renin from the juxtaglomerular cells. The decreased Na concentration in the distal convoluted tubule is believed to be a stimulus for unique ion-transporting molecules  expressed on the apical membrane of macula densa cells. These molecules include Na/2Cl /K cotransporters, Na/H exchangers, and pHand calcium-regulated K channels. Activation of membrane transport pathways changes the intracellular ion concentration within the macula densa cells and initiates signaling mechanisms by releasing various mediators such as ATP, adenosine, nitric oxide (NO), and prostaglandins (PGE2). These molecules act in a paracrine manner and signal both the underlying juxtaglomerular cells of the afferent arteriole to secrete renin and the vascular smooth muscle cells to contract. An increase in blood volume sufficient to cause stretching of the juxtaglomerular cells in the afferent arteriole may be the stimulus that closes the feedback loop and stops secretion of renin.
As the glomerular ultrafltrate passes through the uriniferous and collecting tubules of the kidney, it undergoes changes that involve both active and passive absorption, as well as secretion.
Certain substances within the ultrafiltrate are reabsorbed, some partially (e.g., water, sodium, and bicarbonate) and some completely (e.g., glucose).
Other substances (e.g., creatinine and organic acids and bases) are added to the ultrafiltrate (i.e., the primary urine) by secretory activity of the tubule cells.
Thus, the volume of the ultrafiltrate is reduced substantially, and the urine is made hyperosmotic. The long loop of Henle and the collecting tubules that pass parallel to similarly arranged blood vessels, the vasa recta, serve as the basis for the countercurrent multiplier mechanism that is instrumental in concentrating the urine, thereby making it hyperosmotic.
The proximal convoluted tubule is the initial and major site of reabsorption.
The proximal convoluted tubule receives the ultrafiltrate from the urinary space of Bowman’s capsule. The cuboidal cells of the proximal convoluted tubule have the elaborate surface specializations associated with cells engaged in absorption and fluid transport. They exhibit the following features:  A brush border, composed of relatively long, closely packed, and straight microvilli (Fig. 20.17)  A junctional complex, consisting of a narrow, tight junction that seals off the intercellular space from the lumen of the tubule and a zonula adherens that maintains the adhesion between neighboring cells  Plicae or folds located on the lateral surfaces of the cells, which are large flattened processes, alternating with similar processes of adjacent cells (see Fig. 20.16)  Extensive interdigitation of basal processes of adjacent cells (Figs. 20.18 and 20.19)  Basal striations, consisting of elongate mitochondria concentrated in the basal processes and oriented vertically to the basal surface (see Fig. 20.18)
In well-fixed histologic preparations, the basal striations and the apical brush border help to distinguish the cells of the proximal convoluted tubule from those of the other tubules.
At the very base of the proximal convoluted tubule cell, in the interdigitating processes, bundles of 6-nm microfilaments
FIGURE 20.17 • Drawing of proximal convoluted tubule cells.