1. Nitric oxide (NO) is a potent endogenous vasodilator and plays a role in the control of resting vascular tone. Patients with cirrhosis have a hyperdynamic circulation with reduced blood pressure and decreased peripheral resistance, and it is possible that increased production of NO due to induction of NO synthase may be involved in maintaining this vasodilatation. We have examined this possibility by studying the effects of local infusions of NG-monomethyl-l-arginine (an inhibitor of NO synthase) in the forearm arteriolar bed and the superficial dorsal hand veins of patients with alcoholic cirrhosis.
2. Drugs were either infused locally into the brachial artery and forearm blood flow was measured by venous occlusion plethysmography, or into a vein on the back of the hand and vein diameter was measured using a linear displacement technique.
3. Basal forearm blood flow was increased and vascular resistance was decreased in the patients with alcoholic cirrhosis compared with healthy control subjects. Noradrenaline and NG-monomethyl-l-arginine caused dose-dependent falls in forearm blood flow in both healthy control subjects and patients with cirrhosis. There was no significant difference in the responses to either noradrenaline or NG-monomethyl-l-arginine between the two groups.
4. In the superficial hand veins there was no change in vein size in response to NG-monomethyl-l-arginine infused alone, and venoconstriction to local infusion of noradrenaline was unaffected by co-infusion with NG-monomethyl-l-arginine.
5. Our results confirm that patients with alcoholic cirrhosis are vasodilated compared with healthy control subjects. Our findings show that basal NO-mediated vasodilatation occurs in the forearm arterial bed, but not the superficial hand veins, of these patients. However, since the response to local NO synthesis inhibition was similiar in the two groups, increased production of NO due to induction of NO synthase is unlikely to account fully for the vasodilatation seen in patients with mild to moderate alcoholic cirrhosis.