Nitric oxide (NO) has diverse physiological and pathophysiological effects. The roles of NO in the renal and cardiac dysfunction found in cirrhosis are reviewed. In the kidneys of experimental animals with cirrhosis, several lines of evidence speak in favour of an enhanced production of NO, through the activation of both endothelial constitutive and inducible isoforms of NO synthase. In contrast with the situation in normal animals, inhibition of NO synthesis in rats with cirrhosis improves sodium and water excretion via blood pressure-dependent and -independent mechanisms, which indicates that the renal sodium and water retention of cirrhosis is related to an excess of NO production. The deleterious effect of excessive NO on the kidney may be mediated by peroxynitrite, a potent oxidant that is readily formed whenever superoxide anions and the ·NO radical are produced together. The peroxidation of arachidonic acid by peroxynitrite leads to the formation of F2a-isoprostanes, which are powerful renal vasoconstrictors. F2a-isoprostane levels are correlated with the severity of liver injury during cirrhosis. However, whether peroxynitrite or F2a-isoprostanes are the elusive mediator of the NO-induced renal alterations in cirrhosis remains to be firmly established. NO is also involved in cardiac contractility, probably in the normal heart as well as in disease conditions such as non-cirrhotic and cirrhotic cardiomyopathy. In the latter state, evidence suggests that inducible NO synthase attenuates ventricular contractility, mediated by cGMP. Another gas that transduces its signal through cGMP, carbon monoxide, is also likely to play a role in cirrhotic cardiomyopathy, but the nature of the interaction between NO and carbon monoxide in this syndrome remains unclear.
Review Article| January 14 2002
Nitric oxide and renal and cardiac dysfunction in cirrhosis
M. Clara ORTIZ;
Clin Sci (Lond) (2002) 102 (2): 213-222.
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Joaquín GARCÍA-ESTAÑ, M. Clara ORTIZ, Samuel S. LEE; Nitric oxide and renal and cardiac dysfunction in cirrhosis. Clin Sci (Lond) 1 February 2002; 102 (2): 213–222. doi: https://doi.org/10.1042/cs1020213
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