Abstract
We evaluated the possible alterations produced by liver cholestasis (LC), a model of decompensated liver cirrhosis in sympathetic, sensory and nitrergic nerve function in rat superior mesenteric arteries (SMA). The vasoconstrictor response to electrical field stimulation (EFS) was greater in LC animals. Alpha-adrenoceptor antagonist phentolamine and P2 purinoceptor antagonist suramin decreased this response in LC animals more than in control animals. Both non-specific nitric oxide synthase (NOS) L-NAME and calcitonin gene related peptide (CGRP) (8-37) increased the vasoconstrictor response to EFS more strongly in LC than in control segments. Vasomotor responses to noradrenaline (NA) or CGRP were greater in LC segments, while NO analogue DEA-NO induced a similar vasodilation in both experimental groups. The release of NA was not modified, while those of ATP, nitrite and CGRP were increased in segments from LC. Alpha 1 adrenoceptor, Rho kinase (ROCK) 1 and 2 and total myosin phosphatase (MYPT) expressions were not modified, while alpha 2B adrenoceptor, nNOS expression and nNOS and MYPT phosphorylation were increased by LC. Together, these alterations might counteract the increased splanchnic vasodilation observed in the last phases of decompensated liver cirrhosis.
Highlights
Hypertension[22,23] or diabetes[24,25] can modify the participation of the different neurotransmitters involved in the maintenance of vascular tone
The present study in an experimental model of obstructive liver cholestasis (LC) shows an increase in electric field stimulation (EFS)-induced vasoconstriction in superior mesenteric artery that is the net effect of 1) increased sensitivity to NA through enhanced alpha 2B adrenoceptor expression and ROCK activity, and augmented ATP release, and 2) elevated neuronal nitric oxide (NO) and CGRP releases from the nitrergic and sensory innervations, respectively
As we have previously described in this experimental model, LC animals develop liver fibrosis and hepatomegaly, together with a mean arterial pressure decrease, portal hypertension (PH), enlarged spleen and collateral portosystemic circulation, as well as hepatomegaly, liver encephalopathy and ascites[38,39,40]; these alterations make this an appropriate experimental model for studying alterations associated to decompensated liver cirrhosis
Summary
Hypertension[22,23] or diabetes[24,25] can modify the participation of the different neurotransmitters involved in the maintenance of vascular tone. We have previously described a rearrangement of participation by the different components of perivascular mesenteric innervation in a model of long-term PH21. To the best of our knowledge, possible alterations in the function of perivascular innervation components in decompensated liver cirrhosis have yet to be studied. In light of this background, the aim of this study was to analyse the possible alterations in the vasomotor response to electric field stimulation (EFS) in rat superior mesenteric artery, and how sympathetic, sensory and nitrergic components could be affected in decompensated liver cirrhosis induced by liver cholestasis
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