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Portal hypertension: serotonin and pathogenesis.

D Lebrec1

  • 1Unité de Recherches de Physiopathologie Hépatique (INSERM U-24) Hôpital Beaujon, Clichy, France.

Cardiovascular Drugs and Therapy
|January 1, 1990
PubMed
Summary

Serotonin (5-hydroxytryptamine; 5HT) may worsen portal hypertension. Blocking 5HT2 receptors with drugs like ketanserin and ritanserin effectively reduced portal pressure in patients and animals.

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Area of Science:

  • Pharmacology
  • Gastroenterology
  • Vascular Biology

Background:

  • Serotonin (5-hydroxytryptamine; 5HT) potentially mediates intestinal vasodilation and increases portal vascular resistance.
  • Mesenteric veins in portal hypertensive rats exhibit heightened responsiveness to 5HT, suggesting its role in hyperkinetic syndrome.
  • The hypothesis posits that 5HT increases splanchnic blood flow, contributing to elevated portal pressure.

Purpose of the Study:

  • To investigate the efficacy of 5HT receptor antagonists in reducing portal hypertension.
  • To explore the role of serotonin in the pathophysiology of portal hypertension.

Main Methods:

  • Acute and continuous administration of ketanserin, a 5HT2 receptor antagonist, in cirrhotic patients.
  • Administration of ritanserin, a selective 5HT2 receptor antagonist, in cirrhotic patients.
  • Administration of ketanserin and ritanserin in rats with experimentally induced portal hypertension.

Main Results:

  • Ketanserin significantly decreased portal pressure and collateral blood flow in cirrhotic patients without affecting hepatic blood flow.
  • Ketanserin caused a slight decrease in arterial pressure but did not alter cardiac output.
  • Ritanserin also significantly reduced portal pressure in cirrhotic patients and portal hypertensive rats.
  • In rats, 5HT2 antagonists reduced portal pressure by potentially acting on hepatocollateral vascular resistance.

Conclusions:

  • Serotonin's action via 5HT2 receptors plays a significant role in portal hypertension.
  • 5HT2 receptor antagonists represent a promising new class of drugs for treating portal hypertension.
  • Targeting 5HT2 receptors offers a potential therapeutic strategy for managing portal hypertension and its complications.

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