Peripheral vascular tone in patients with cirrhosis: role of the renin-angiotensin and sympathetic nervous systems.
OBJECTIVE
The aims of the study were to establish the roles of angiotensin II and of the cardiopulmonary baroreceptor reflex in the regulation of peripheral vascular tone in patients with cirrhosis.


METHODS
Forearm blood flow responses to subsystemic, locally active intrabrachial infusions were measured in patients with Child's Grade C cirrhosis and matched controls using bilateral venous occlusion plethysmography. Responses were determined to the angiotensin II type I receptor antagonist, losartan, noradrenaline, angiotensin II and the nitric oxide synthase inhibitor, L-NG-monomethyl arginine.


RESULTS
Losartan at 30 and 90 micrograms/min caused no significant change in blood flow in controls, but caused 23 +/- 6% and 27 +/- 5% increases in patients respectively (p < 0.001). Lower body negative pressure caused a mean bilateral reduction in forearm blood flow of 20 +/- 4% in controls (p < 0.001) but only tended to reduce flow (9 +/- 5%; p = 0.06) in patients (p < 0.001; controls vs. patients). Noradrenaline, angiotensin II and L-NG-monomethyl arginine caused significant vasoconstriction (p < 0.001) in both patients and controls although angiotensin II caused significantly less vasoconstriction in patients (p = 0.01).


CONCLUSIONS
We conclude that angiotensin II makes an important contribution to basal peripheral vascular tone in patients with cirrhosis in the face of reduced vascular responses to its local administration. In addition, the vasoconstrictor response to cardiopulmonary baroreceptor unloading is attenuated despite normal vascular responses to noradrenaline. These responses are consistent with chronic activation of the renin-angiotensin and sympathetic nervous systems in patients with advanced cirrhosis.
Clinical Pharmacology Unit, University of Edinburgh, Western General Hospital, Scotland, UK. d.e.newby@ed.ac.uk
D E
DE
Newby
R
R
Jalan
S
S
Masumori
P C
PC
Hayes
N A
NA
Boon
D J
DJ
Webb
D000704:Analysis of Variance; D000804:Angiotensin II / Q000494:pharmacology / Q000502:physiology*; D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents / Q000494:pharmacology; D005260:Female; D005542:Forearm / Q000098:blood supply*; D006801:Humans; D008103:Liver Cirrhosis / Q000503:physiopathology*; D019808:Losartan / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009638:Norepinephrine / Q000494:pharmacology; D010991:Plethysmography; D012039:Regional Blood Flow / Q000187:drug effects; D012084:Renin-Angiotensin System / Q000502:physiology*; D013564:Sympathetic Nervous System / Q000503:physiopathology*; D013566:Sympathomimetics / Q000494:pharmacology; D014655:Vascular Resistance / Q000502:physiology*; D019323:omega-N-Methylarginine / Q000494:pharmacology
D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D013566:Sympathomimetics; D000804:Angiotensin II; D019323:omega-N-Methylarginine; D019001:Nitric Oxide Synthase; D019808:Losartan; D009638:Norepinephrine