Kidney macula densa

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. 

Cyclooxygenase (COX) activity is responsible for the formation of prostaglandins from their arachidonic acid precursor. Two COX isoforms have been identified, COX-1 and COX-2. While COX-1 is constitutively expressed in most tissues, COX-2 is typically only found after induction by proinflammatory stimuli. However, a constitutively expressed and highly regulated COX-2 is found in the kidney, both in the renal medulla and in the renal cortex. Renal cortical COX-2 is located in the area ofthe juxtaglomerular apparatus, and prostaglandins formed by COX-2 regulate the expression and secretion of renin in response to a reduction in NaCl concentration at the macula densa. 

Constitutive Inducible in neurons, macula densa of kidney testes and female reproductive system also contain constitutive COX-2... 

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). 

There is another system involved in blood pressure regulation the renin-angiotensin-aldosterone system (Fig. 2). The arterial blood pressure in the kidney influences intrarenal baroreceptors which together with the sodium load at the macula densa lead to renin liberation, angiotensin formation and aldosterone secretion, which by influencing the sodium balance changes the blood volume and influences the arterial blood pressure. 

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). 

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 rate at which renin is secreted by the kidney is the primary determinant of activity of the renin-angiotensin system. Renin secretion is controlled by a variety of factors, including a renal vascular receptor, the macula densa, the sympathetic nervous system, and angiotensin II. 

Ito 5, Carretero OA An in vitro approach to the study of macula densa-mediated glomerular hemodynamics. Kidney Int 38 1206-1210,1990... 

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. 

Elarris RC, McKanna JA, Akai Y et al. Cyclooxygenase-2 is associated with the macula densa of rat kidney and increases with salt restriction. Journal of Clinical Investigation 1994 94 2504-2510. 

In normal rat and dog kidney COX-2 is sparsely expressed in the macula densa, but expression is upregulated when animals are volume depleted. Selective COX-2 inhibitors have been discovered but it is not known what the effects of these drugs will be on renal homeostasis. Acute interstitial nephritis has been described with COX-2 inhibitors. ... 

Control of renin release from the Icidney is influenced by (1) specialized cells in the distal convoluted tubules called the macula densa function as cliemoreceptors for the concentration of sodium delivered to the distal tubules (2) juxtaglomerular cells functioning as mini pressure transducers sense the renal perfusion pressure in the kidney (3) the sympathetic nervous system that feeds the kidney and catecholamine release and (4) humoral factors such as potassium, atrial natriuretic peptides, and angiotensin II. All of these influences are involved in the normal control of salt and water balance and with diseases of the kidney. Secondary... 

The list of neurons that possess nNOS continues to expand (Vincent and Hope, 1992 Bredt et al., 1991). For example, NO has emerged as a major nonadrenergic noncholinergic transmitter in the enteric nerves (Bult etal., 1990 Desai etal., 1991). In addition to the nervous system, immunore-activity and/or mRNA transcript for nNOS have been detected in skeletal muscle (Nakaneeta/., 1993 Weiner eta/., 1994), pancreatic )8-ceils (Schmidt et al., 1992), the male sex organ (Burnett et al., 1992), the pituitary gland (Wolff and Datto, 1992), the adrenal medulla (Afework et al., 1994 Dun et al., 1993), and the macula densa and distal nephron of the kidneys (Mundel et al., 1992 Terada et al., 1992 Wilcox et al., 1992). Therefore, nNOS is expressed in diverse cell types and tissues. 

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