Local arterial vasoconstriction induced by octreotide in patients with cirrhosis.
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 microg/min; octreotide 20 microg/h, and octreotide 20 microg/h + methacholine 4 microg/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 (%triangle up) 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 <.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.
Chatila
R
R
Section of Digestive Diseases, Yale University School of Medicine, and the Hepatic Hemodynamic Laboratory at the Veterans Administration Medical Center, West Haven, CT 06516, USA.
Ferayorni
L
L
Gupta
T
T
Groszmann
R J
RJ
D001132:Arm; D005260:Female; D005934:Glucagon / Q000097:blood; D006801:Humans; D007261:Infusions, Intra-Arterial; D008103:Liver Cirrhosis / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology; D015282:Octreotide / Q000097:blood / Q000494:pharmacology*; D012039:Regional Blood Flow / Q000187:drug effects; D014661:Vasoconstriction; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D014662:Vasoconstrictor Agents; D016210:Methacholine Chloride; D005934:Glucagon; D015282:Octreotide