These results were associated with increased expression of endothelin-1 and its receptor, together with e-NOS up-regulation as potential mechanisms of protection. Taking into account these experiments, it is plausible
that CIH effects on vascular reactivity could be attenuated in the CBDL model, such as in sustained chronic hypoxia. On the other hand, further vasoconstriction to Mtx was observed in both models of cirrhosis after CIH. Our results suggest that additional factors STA-9090 cell line may play a role in this response. Particularly, increased production of endothelin-1 has been found to occur during CIH.34 To our knowledge, this is the first experimental study investigating the hepatic hemodynamic effects of CIH in the setting of cirrhosis. Our novel findings are clinically relevant, because CIH and OSAS have been described in patients with cirrhosis and portal hypertension. A pilot study showed a previously undescribed high prevalence of OSAS and nocturnal oxygen desaturations among patients who have cirrhosis with ascites that improved after paracenthesis.10 This observation has been
confirmed by other groups more recently.11, 13 The results of these studies showed that OSAS can be present in cirrhotic patients and particularly in those with severe liver disease, which could exacerbate impairment of liver function. In fact, OSAS has been associated with elevated alanine aminotransferase levels in patients12 and animals exposed to CIH.35 Furthermore, even severe histology changes (inflammation and fibrosis) have been shown to appear after long exposure to GSK-3 inhibitor review CIH.35 In our short-term experimental conditions, MCE the
absence of change in baseline portal perfusion pressure makes a change in intrahepatic mechanical vascular resistance unlikely due to increased fibrosis. In vivo baseline hemodynamic parameters were not significantly different between CIH and HC rats. However, after volume expansion was performed in cirrhotic rats, analysis of hemodynamics yielded interesting results. As shown by other investigators,16, 36 after volume expansion in cirrhotic rats, PP increases as MAP and portal blood flow augments, due to the inability of the liver circulation to appropriately dilate in response to flow. In fact, this further increase in PP can be prevented with NO donors16, 36 without modifying MAP or portal blood flow. In our study, PP increase was similar in CIH and HC rats. However, MAP and probably PBF increase were lower in CIH rats. Indeed, vascular hyporeactivity due to autonomic impairment has been described recently after exposure to CIH.37 These observations suggest that CIH may also provoke additional deleterious systemic effects in cirrhotic rats, yet to be studied. Overall, these data suggest that CIH could be a relevant underestimated factor to take into account when assessing cirrhotic patients with portal hypertension.