Increased hepatic resistance: a new target in the pharmacologic therapy of portal hypertension.
Increased resistance to portal blood flow is the primary factor in the pathophysiology of portal hypertension, and is mainly determined by the morphologic changes occurring in chronic liver diseases. This is aggravated by an increased hepatic vascular tone, which results from an insufficient hepatic bioavailability of nitric oxide (NO) and an increased production of circulating and local vasoconstrictors (angiotensin, endothelin, cysteinyl-leukotrienes, and thromboxane, among others). This dynamic and reversible component provides the rationale for the use of therapies aimed at decreasing portal pressure by reducing the vascular tone. Among them, systemic and liver-selective NO donors, statins, and gene therapy with adenovirus encoding NO synthases have been used to increase NO availability with promising results. Other attempts have been the blockade of the effect of vasoconstrictors, using anti alpha-adrenergic agents and renin-angiotensin system blockers. Some of these pharmacologic approaches have already been incorporated into clinical practice while others are still under investigation.
Hernández-Guerra
Manuel
M
Hepatic Hemodynamic Laboratory, Liver Unit, Institut de Malalties Digestives, Hospital Clínic, IDIBAPS, University of Barcelona, Barcelona, Spain.
García-Pagán
Juan Carlos
JC
Bosch
Jaime
J
D000317:Adrenergic alpha-Antagonists / Q000627:therapeutic use; D002121:Calcium Channel Blockers / Q000627:therapeutic use; D016232:Endothelins / Q000037:antagonists & inhibitors; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D006975:Hypertension, Portal / Q000188:drug therapy* / Q000503:physiopathology; D008099:Liver / Q000098:blood supply* / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000627:therapeutic use; D012084:Renin-Angiotensin System / Q000187:drug effects; D014655:Vascular Resistance / Q000502:physiology*
D000317:Adrenergic alpha-Antagonists; D002121:Calcium Channel Blockers; D016232:Endothelins; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D020030:Nitric Oxide Donors; D009569:Nitric Oxide