Nitric oxide mediates the reduced vasoconstrictor response to angiotensin II in patients with preascitic cirrhosis.
OBJECTIVE
Altered vascular responses to vasopressor agents contribute to the pathogenesis of the circulatory dysfunction in cirrhosis. This study aims to assess the role of endogenous nitric oxide (NO) in the reduced vascular responsiveness to angiotensin II (ANG-II) in eight patients with preascitic cirrhosis compared with eight age- and sex-matched healthy controls.


METHODS
Forearm blood flow (FBF) responses to sub-systemic, locally-active intra-brachial infusions of ANG-II were measured using venous occlusion plethysmography before and during the application of an 'NO-clamp', a balanced co-infusion of L-N(G)-monomethyl-arginine (a selective NO synthase inhibitor) and sodium nitroprusside (an exogenous NO donor) to block endogenous NO production and restore normal NO-mediated basal blood flow, respectively.


RESULTS
Before applying the 'NO-clamp', ANG-II caused dose-dependent reductions of FBF in both groups (P<0.001) that were significantly attenuated in the cirrhotic patients (P=0.012). In the presence of the 'NO-clamp', the ANG-II-mediated vasoconstriction was enhanced in cirrhotic patients (P<0.01), unchanged in controls, and now similar in both groups.


CONCLUSIONS
This study confirms that vasoconstriction to ANG-II is reduced in patients with preascitic cirrhosis, and suggests that this is principally due to enhanced NO generation mediated by ANG-II.
Helmy
Ahmed
A
Liver Unit, Department of Medicine, Royal Infirmary of Edinburgh, Edinburgh, UK.
Newby
David Ernest
DE
Jalan
Rajiv
R
Johnston
Neil Russell
NR
Hayes
Peter Clive
PC
Webb
David John
DJ
D000804:Angiotensin II / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D001201:Ascites; D016022:Case-Control Studies; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005542:Forearm / Q000098:blood supply; D006801:Humans; D008103:Liver Cirrhosis / Q000097:blood / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism*; D012039:Regional Blood Flow / Q000187:drug effects; D014661:Vasoconstriction; D014662:Vasoconstrictor Agents / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D019323:omega-N-Methylarginine / Q000494:pharmacology
D004791:Enzyme Inhibitors; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D019323:omega-N-Methylarginine; D009569:Nitric Oxide