Physiopathologie de l'hyporéactivité vasculaire au cours des états de choc

Several mechanisms have been proposed to explain the pathophysiology of vascular failure induced by shock states. Nitric oxide (NO), which is produced in excess by inducible nitric oxide synthase (iNOS), is one of the crucial components implicated in vasoplegia and vascular hyporeactivity. NO may cause vasodilatation, notably via the GMPc pathway, by interacting with superoxide to produce peroxynitrite (peroxynitrite interacts with lipids, DNA and proteins via direct or indirect radical-mediated mechanisms) and by activating ATP-sensitive potassium (KATP) channels and calcium-activated potassium (KCa) channels. Potassium channels have a role in coupling membrane excitability with metabolism. They are also activated by peroxynitrite, a fall in ATP, acidosis, hypoxia and lactate, all of which are commonly present in shock. Experimental and clinical data have demonstrated that the induced hyperpolarisation is partially responsible for the hypovasoreactivity observed during shock states. Vasopressin is a vasoconstricting hormone which can inhibit potassium channels as well as NO effects and can potentialize the effects of vasopressor drugs. However, during septic shock, plasma vasopressin concentration is inappropriately low. In addition, shock state is characterized by an alphareceptor dysfunction and desensitization (uncoupling, down regulation), an inactivation of catecholamines by oxidation and by high concentrations of adrenomedullin, a potent vasodilatory agent. While there are currently no specific therapeutic approches, high doses of catecholamines, vasopressin, glucocorticoids, activated protein C and sepsis treatment have nevertheless demonstrated a partial efficiency in reversing sepsis-induced hypotension.