Macula densa cells

A correlation between the activity of G-6-PDH and extractable renin in rat kidneys has been reported, suggesting that the macula densa cells and also the juxtaglomerular apparatus are parts of a system related to the formation of renin (H6). 

Increased delivery of salt to the TAL leads to activation of the macula densa and a reduction in glomerular filtration rate (GFR) by tubuloglomerular (TG) feedback. The mechanism of this feedback is secretion of adenosine by macula densa cells, which locally causes afferent arteriolar vasoconstriction. This vasoconstriction reduces GFR. Tubuloglomerular feedback-mediated reduction in GFR exacerbates the reduction that was initially caused by decreased cardiac output. Recent work with adenosine receptor antagonists (eg, rolofylline) has shown that it will soon be possible to circumvent this complication of diuretic therapy in heart failure patients. Using rolofylline with a diuretic will make it possible to produce an effective diuresis in patients with heart failure without causing renal decompensation. 

Schlatter (1993) recorded membrane voltages of macula densa cells with the fast or slow whole-cell patch-clamp method. The effects of diuretics and the conductance properties of these cells were examined. 

Schlatter E (1993) Effect of various diuretics on membrane voltage of macula densa cells. Whole-cell patch-clamp experiments. Pfliigers Arch Eur J Physiol 423 74-77... 

In each case the sulfated metabolite undergoes active tubular. secretion by the OATS in proximal tubular cells and. hence, attains high levels in luminal fluid. The negatively charged sulfate moiety pruhably hinds to the Cr-binding. site on (he luminal membrane-bound INa /IK /2CI co-tran-sport. system of (hick ascending limb and macula densa cells. 

Mundel, P., Bachmann, S., Bader, M., Fischer, A., Kummer, W., Mayer, B., and Kriz, W. (1992). Expression of nitric oxide synthase in kidney macula densa cells. Kidney Int. 42, 1017-1019. 

Structural differences of macula densa cells among species concern essentially cell height and amount of mitochondria. In rabbits, the macula densa cells are densely stuffed with small mitochondria and are a prominent plaque of distinctly taller cells than the thick ascending Umb cells (Kaissling and Kriz 1979). In rat (Kaissling and Kriz 1982), mice, and Psammomyys, species with a greater capacity for urinary concentration, the macula densa cells are less or not all prominent and possess only a very few mitochondria. 

NOS I is predominantly localized in macula densa cells, while NOS III is found endothehal cells of arteries, arterioles and glomerular capillaries (Bachmann etal. 1995). In order to characterize the promoters active in the macula densa and to study the regulation of NOS I expression in these cells, Oberbaumer etal. (1997) cloned the 5 ends of NOS I from rat kidney by RT-PCR. They found that the two alternative first exons of brain NOS I were not contained in the main NOS I mRNA from kidney. 

Fig. 318. Macula densa cells from the kidney (block BNh 3372) of a male Wistar rat (No.2567) 90 min after a single in-traperitoneal injection of 5 mg AT-benzhydryl-JV-p-hydroxy-benzylpiperazine HCl per kg body weight. Under pentobarbital anaesthesia (30 mg/kg), the animal was perfused from the abdominal aorta with 2.5% glutaraldehyde in 0.1 M sodium cacodylate buffer (pH 7.4). Postfixation with 1 % osmium tet-roxide in sodium cacodylate buffer. Embedded in Epon 812 and sectioned at 50 nm. Lead citrate and uranyl acetate. Plate 2453...

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. 

OTRs are mainly expressed in myoepithelial cells of the galactiferus channels and the myometrium. The OTRs in vascular endothelial cells, renal epithelial cells (macula densa, proximal tubule) and cardiomyocytes induce the production of NO (vasodilation), natriuresis and release of ANP, respectively. The endometrium, ovary, amnion, testis, epididymis, prostate and thymus also express the OTR supporting a paracrine role of this peptide. Osteoblasts, osteoclasts, pancreatic islets cells, adipocytes, and several types of cancer cells also express OTRs. More over, expression of the OTR... 

An increase in MAP leads to an increase in RBF, PGC/ and GFR. As a result, the rate of fluid flow through the distal tubule increases, leading to an increase in reabsorption of Na+ and Cl ions by the cells of the macula densa in the distal tubule. Consequently, these cells release vasoconstrictor substances, primarily adenosine. The subsequent increase in the resistance of the nearby afferent arteriole decreases RBF to normal and, as a result, PGC and therefore GFR decrease to normal. In this way, the distal tubule regulates its own filtrate flow. 

Renin is secreted into the bloodstream by specialised cells in a portion of the distal tubules in the kidney (known as the macula densa). The rate of secretion is stimulated by several factors, including a low Na" ion concentration in the blood and an increase in sympathetic activity (i.e. an increase in the local level of noradrenaline). 

Increased NaCl at macula densa in distal tubule leads to decreased renin release by JG cells. 

Both the medulla and the cortex of the kidney synthesize prostaglandins, the medulla substantially more than the cortex. COX-1 is expressed mainly in cortical and medullary collecting ducts and mesangial cells, arteriolar endothelium, and epithelial cells of Bowman s capsule. COX-2 is restricted to the renal medullary interstitial cells, the macula densa, and the cortical thick ascending limb. 

The macula densa contains a different type of receptor, sensitive to changes in the rate of delivery of sodium or chloride to the distal tubule. Decreases in distal delivery result in stimulation of renin secretion and vice versa. Potential candidates for signal transmission between the macula densa and the juxtaglomerular cells include adenosine, prostaglandins, and nitric oxide. 

Clark, A. F., Sharp, M., Morlcy, S. D., Fleming, S Peters, J and Mullins, J. J. (1997). Renin-1 is essential (or normal renal juxtaglomerluar cell granulation and macula densa morphology /. Bibf. Cfierfi. 272,18183-18190. 

Distribution of the COX-2 isoform in the adult human kidney is based upon in-situ hybridization and immunolocation studies [11]. COX-2 has been detected in both the macula densa and medullary interstitial cells in patients with Bartter s syndrome and congestive heart failure [22] as well as in elderly patients. COX-1, in addition to being expressed in the glomerulus, is constitutively expressed in both the cortical and medullary collecting ducts [15,16] (Figure 2). The exact role of the duel expression of both COX isoforms in the medullary collecting duct remains to be elucidated. 

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