CARDIAC AND RENAL NITRIC OXIDE IN THE ADAPTATION TO HYPOVOLEMIC SHOCK

FELLET A.; BOVERIS A.; ARRANZ C; BALASZCZUK A.

Current Enzyme Inhibition

Bentham Science Publishers Ltd.

Año: 2009 vol. 5 p. 176 - 183

1573-403X

The discovery that mammalian cells synthesize nitric oxide (NO) and the numerous physiological functions regulated by NO have stimulated an extraordinary interest in the NOmediated biochemical and physiological mechanisms that operate in almost all fields of biology and medicine. Since its early description as the endothelium-derived relaxing factor, NO emerged as a fundamental signaling molecule involved in the regulation of critical cellular functions as well as a potent mediator of cellular damage in a wide range of pathophysiological conditions. Evidence is mounting that NO plays a role in the cardiovascular and renal adaptation to the hemorrhagic shock secondary to major blood loss. This hypovolemic state leads to activation of a complex neurohumoral response associated with peripheral vasoconstriction and with a redistribution and maintenance of blood flow to vital organs such as heart and kidney. Recently, we reported cardiac and renal NO-dependent protective mechanisms activated by the hypovolemic state that include stimulation of NO synthase (NOS) expression and activity. In the heart, an increase in endothelial NOS is an early response to regulate cardiac function after blood loss. Meanwhile, inducible NOS increases heart dysfunction in later stages of sustained hemorrhagic shock. Additionally, the hypovolem ic state induced changes in water homeostasis associated with alterations in inner medullary aquaporin water channel type 2 (AQP2) protein expressions and subcellular localization. NO production is one of the cause of the age-associated response that modulates AQP2 expression/trafficking in the inner collecting duct principal cells in response to hemorrhage. The complex regulation of NOS in cardiovascular and renal physiology depends on the magnitude of hemorrhage and age. The effects of endogenous and exogenous NO on cardiovascular and renal function have gained great interest considering both the development of physiological knowledge and the eventual extension of the new concepts to the pharmacological and therapeutical fields for the treatment of tissue dysfunction using NO donors, inhibitors of NO endogenous production and inhibitors of the shut-off mechanisms for NO effects. The adaptive enhancement of NO synthesis and availability activates or increases expression of other protective factors, including heat shock proteins, antioxidants and prostaglandins, making the protection more robust and sustained. This review focuses on the biochemical and physiological mechanisms that involve NOS expression and activity in the heart and kidney in hypovolemic shock. Understanding the role of NO in the mechanisms of adaptation to hemorrhage will support the development of therapies to prevent and to treat hypoperfusion damage to organs and cells and to increase the adaptive capabilities of the organism.