The future treatment of portal hypertension.
Increased understanding of the hyperdynamic circulation syndrome has resulted in novel therapeutic approaches, some of which have already reached clinical practice. Central to the hyperdynamic circulation syndrome is an imbalance between the increase in different vasodilators (foremost among which is nitric oxide) and the compensatory increase in vasoconstrictors--usually accompanied by a blunted response. This chapter discusses the role of endothelin in the pathogenesis of the syndrome and in future treatment approaches. A relatively new area of research in this field is the role of infection and inflammation in the initiation and maintenance of the hyperdynamic circulation syndrome. The use of antibiotics in the setting of acute variceal bleeding is standard practice. Studies have suggested that chronic manipulation of the intestinal flora could have beneficial effects in the treatment of portal hypertension. The bile salts are another novel and interesting target. Although their vasoactive properties have been known for some time, recent data demonstrate that their effects could be central in the pathogenesis of the hyperdynamic circulation syndrome, and that manipulation of the composition of the bile acid pool could be a therapeutic approach to portal hypertension. Finally, hypoxia and angiogenesis play a role in the development of portal hypertension and the formation of collaterals. This role needs to be further defined but it appears likely that this phenomenon is yet another target for therapeutic intervention.
Reichen
Jürg
J
Institute of Clinical Pharmacology, University of Berne, Murtenstrasse 31 POB 49, 3010 Berne, Switzerland. reichen@ikp.unibe.ch
Lebrec
Didier
D
D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001647:Bile Acids and Salts / Q000097:blood; D004359:Drug Therapy, Combination; D016232:Endothelins / Q000502:physiology*; D006801:Humans; D006975:Hypertension, Portal / Q000188:drug therapy* / Q000209:etiology* / Q000382:microbiology; D009389:Neovascularization, Pathologic / Q000150:complications; D009569:Nitric Oxide / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000502:physiology
D000900:Anti-Bacterial Agents; D000893:Anti-Inflammatory Agents; D001647:Bile Acids and Salts; D016232:Endothelins; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase