Renal natriuretic factor

In 1989 a renal natriuretic factor (RNF) was detected for the first time and termed urodilatin (P. Schulz-Knappe et at). As examinations have hitherto shown, urodilatin is formed in the medial nephron of the kidney and causes a distad inhibition in the absorption of water and sodium. Its half-life is likewise about 3 minutes. Although ANF is most probably of limited significance for the excretion of sodium and its influence on sodium homoeo-stasis in cases of liver cirrhosis (with or without ascites) has still not been fully clarified, urodilatin is deemed to be important for the regulation of the water and electrolyte balance. (3) (s. tab. 16.5)... 

Wong NLM, Wong EEC (1992) Effect of dietary sodium on atrial natriuretic factor released in rats with chronic renal failure. Nephron 61 464-469... 

Lenz, K., Hortnagl, H., Druml, W., Reither, H., Schmid, R., Schneeweiss, B., Laggner, A., Grimm, G., Gerbes, A.L. Ornipressin in the treatment of functional renal failure in decompensated liver cirrhosis. Effects on renal hemodynamics and atrial natriuretic factor. Gastroenterology 1991 101 1060-1067... 

Lieberthal W, Sheridan AM, Valeri CR Protective effect of atrial natriuretic factor and mannitol following renal ischemia. Am J Physiol 258 1266-72,1990... 

Kharasch ED, Yeo KT, Kenny MA, Buffington CW. Atrial natriuretic factor may mediate the renal effectsof PEEP ventilation. Anesthesiology 1988 69(6) 862-9. 

Hestin D, Mertes PM, Hubert J, Claudon M, Mejat E, Renoult E, Pertek JP, Frimat E, Burlet C, Kessler M. Relationship between blood pressure and renin, angiotensin II and atrial natriuretic factor after renal transplantation. Clin Nephrol 1997 48 98-103. 

Lang CC, Henderson IS, Mactier R, Stewart WK, Struthers AD. Atrial natriuretic factor improves renal function and lowers systolic blood pressure in renal allograft recipients treated with cyclosporin A. J Hypertens 1992 10 483-488. 

NEP inactivates a series of renal and CNS-active peptides, such as substance P, bradykinin, enkephalins and atrial natriuretic factor. It has been well underlined that inhibitors of NEP should be useful in the treatment of pain because of having a large spectrum of activities similar to that of opioid analgesics. In fact, inhibitors of NEP protect the endogenous atrial natriuretic factor degradation and enhance the typical renal effects of ANF on diuresis and natriuretic response (see Figure 28). 

Endothelial cells are the major source of ET-1-synthesis. ET-1 is also produced by astrocytes, neurons, hepatocytes, bronchial epithelial cells, renal epithelial and mesangial cells. Physiological stimuli of ET-1-synthesis in endothelial cells are angiotensin II, catecholamines, thrombin, growth factors, insulin, hypoxia and shear stress. Inhibitors of ET-1 synthesis are atrial natriuretic peptide, prostaglandin E2 and prostacyclin. ET-2 is mainly synthesized in kidney, intestine, myocardium and placenta and ET-3 is predominantely produced by neurons, astrocytes and renal epithelial cells. 

Hypoperfusion of skeletal muscles leads to fatigue, weakness, and exercise intolerance. Decreased perfusion of the central nervous system (CNS) is related to confusion, hallucinations, insomnia, and lethargy. Peripheral vasoconstriction due to SNS activity causes pallor, cool extremities, and cyanosis of the digits. Tachycardia is also common in these patients and may reflect increased SNS activity. Patients will often exhibit polyuria and nocturia. Polyuria is a result of increased release of natriuretic peptides caused by volume overload. Nocturia occurs due to increased renal perfusion as a consequence of reduced SNS renal vasoconstrictive effects at night. In chronic severe HF, unintentional weight loss can occur which leads to a syndrome of cardiac cachexia. This results from several factors, including loss of appetite, malabsorption due to gastrointestinal edema, elevated metabolic rate, and elevated levels of proinflammatory cytokines. 

In vitro studies suggest that the GRK4 SNPs impair the function of receptors, increase blood pressure, and impair the diuretic and natriuretic effects of dopamine Dj-like agonist stimulation. Inappropriate desensitization of the dopamine D, receptor in renal proximal tubules in hypertension may result in the decreased ability of the kidney to eliminate a sodium chloride load—a key risk factor in the development of hypertension. 

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... 

At least three other groups of factors believed to regulate sodium secretion are neurogenic factors, switches from salt-conserving to salt-wasting nephrons, and natriuretic hormones. When dietary sodium is low, renal excretion decreases within 4 days to levels approaching zero. Reduced renal excretion results in part from aldosterone production. However, a decrease in urinary sodium has been observed with normal levels of aldosterone secretion. Consequently,... 

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