Octreotide potentiates PKC-dependent vasoconstrictors in portal-hypertensive and control rats

Gastroenterology. 2001 Mar;120(4):975-83. doi: 10.1053/gast.2001.22529.


Background & aims: The effect of octreotide on vascular tone in the superior mesenteric artery (SMA) was studied in portal-hypertensive (portal vein-ligated) and sham-operated rats.

Methods: In vitro-perfused SMA vascular beds were tested for the cumulative dose-response to octreotide at baseline conditions and after preconstriction with different vasoconstrictors (alpha1-agonist methoxamine, endothelin [ET-1], phorbol ester [PdBu], and potassium chloride [KCl]).

Results: Octreotide did not affect baseline perfusion pressures (without preconstriction). alpha1-Adrenergic-, ET-1-, and PdBu-, but not KCl-, induced vasoconstriction was significantly potentiated by octreotide. This effect was dose-dependent and not different in portal vein-ligated and sham rats. Amplification of alpha1-adrenergic vasoconstriction by octreotide was significantly enhanced by nitric oxide inhibition (N(W)-nitro-L-arginine, 10(-4) mol/L) as well as by removal of the endothelium, and was completely suppressed by inhibition of protein kinase C (calphostin C, 1 micromol/L), phospholipase A2 (quinacrine, 5 micromol/L), and cyclooxygenase (indomethacin, 20 micromol/L).

Conclusions: Not directly, but in the presence of vasoconstrictors involving activation of protein kinase C, octreotide exerts a local vasoconstrictive effect on vascular smooth muscle of SMA. This potentiation is equipotent in portal vein-ligated and sham rats, immediate in onset, and mediated via phospholipase A2 and cyclooxygenase-derived prostanoids. This indicates that in preprandial conditions octreotide enhances the vasoconstrictive effect of dependent vasoconstrictors.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adrenergic alpha-Agonists / pharmacology
  • Animals
  • Dose-Response Relationship, Drug
  • Drug Synergism
  • Endothelin-1 / pharmacology
  • Endothelium, Vascular / physiopathology
  • Hypertension, Portal / physiopathology*
  • Male
  • Methoxamine / pharmacology
  • Nitric Oxide / physiology
  • Octreotide / pharmacology*
  • Phorbol 12,13-Dibutyrate / pharmacology
  • Protein Kinase C / physiology*
  • Rats
  • Rats, Sprague-Dawley
  • Reference Values
  • Vasoconstrictor Agents / pharmacology*


  • Adrenergic alpha-Agonists
  • Endothelin-1
  • Vasoconstrictor Agents
  • Nitric Oxide
  • Phorbol 12,13-Dibutyrate
  • Protein Kinase C
  • Methoxamine
  • Octreotide