Peripheral vasodilation initiates the hyperdynamic circulation in cirrhosis. Somatostatin and its analogues, such as octreotide, have a vasoconstrictive effect in cirrhotic patients and experimental animals with portal hypertension. The exact mechanism of octreotide-induced vasoconstriction remains unknown. To investigate whether octreotide produces vasoconstriction through suppression of vasodilatory peptides, such as glucagon, or through a local effect, we evaluated the effect of an intra-arterial dose on forearm blood flow (FBF), while measuring systemic glucagon levels. FBF was measured in 10 cirrhotic patients by venous occlusion plethysmography. The brachial artery of the nondominant arm was catheterized, and vasoactive drugs were administered: methacholine 4 g/min; octreotide 20 g/h, and octreotide 20 g/h ؉ methacholine 4 g/min. Each infusion, lasting 5 minutes, was followed by saline for washout. FBF was measured in both arms during the last minute of each infusion and at the end of washout, with the uninfused arm acting as the control. Nitrates and nitrites, octreotide, and glucagon blood levels were determined at baseline and after each infusion. Percent change in flow (%⌬) was obtained by comparing the flow during drug administration to that during the preceding saline infusion. Saline infusion did not alter FBF, but octreotide infusion resulted in a 34% ؎ 7.7 (P F .005) reduction in FBF in the infused arm. FBF in the control arm was unchanged despite a significant decrease in systemic glucagon levels. Methacholine infusion increased FBF around 300%, which was not altered by the concomitant infusion of octreotide. Octreotide has a local vasoconstrictive effect that seems nitric oxide (NO)-independent. Octreotide probably has a facilitating effect over vasoconstrictors increased in chronic liver diseases. (HEPATOLOGY 2000;31:572-576.)Chronic peripheral vasodilation is the hallmark hemodynamic abnormality in portal hypertension, which accounts for several important complications of cirrhosis. 1 This state (characterized by low mean arterial pressure [MAP], increased cardiac output, and increased regional blood flow) has been shown to be, at least in part, caused by increased production of the endothelial vasodilator nitric oxide (NO). [2][3][4][5] Studies of the natural history in patients with cirrhosis clearly illustrate that one of the main predictors of survival in patients with cirrhosis and ascites is the MAP. A low MAP that reflects a state of peripheral arterial vasodilation was directly associated with poor survival rate. 6 As a result, there is an interest in drugs that could modify this state without inducing untoward effects. Octreotide, a long-acting analogue of somatostatin, 7 was introduced for clinical use in patients with cirrhosis and variceal hemorrhage in the early 1990s. 8 Its initial clinical use was mostly based on data about the beneficial effect of somatostatin, its naturally occurring hormone, in this clinical setting. The mechanism by which the systemic administration of somat...
