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Role of protein kinase C in mesenteric pressor responses of rats with portal hypertension.

Abstract
1. Hyporesponsiveness to vasoconstrictors is a characteristic abnormality of liver diseases of uncertain origin. In the present study, we have evaluated the involvement of protein kinase C (PKC) in the reduced pressor response to methoxamine (MTX) of a rat model of portal hypertension induced by partial portal vein ligation (PVL). Experiments were performed in the isolated and perfused mesentery. 2. The pressor response to MTX was reduced in PVL compared to that of control animals (Sham) and pretreatment with NG-nitro-L-arginine (L-NOARG, 10(-4) M) or removal of the endothelium potentiated the response of both groups. However, only removal of the endothelium completely eliminated the reduced pressor response to MTX of the PVL vessels. 3. Pretreatment of the mesentric vessels with calphostin C (10(-6) M), a PKC inhibitor, reduced the response to MTX of Sham to a level similar to that of untreated PVL vessels, but did not change that of PVL animals. 4. Mesenteric pressor responses to a PKC activator, phorbol 12,13-dibutyrate (PDBu), were similar in vessels from both PVL and Sham rats and pretreatment with L-NOARG or removal of the endothelium enhanced those responses while indomethacin (10(-5) M) decreased them. In all cases, the responses to PDBU were similar in PVL vessels compared to Sham. 5. These results indicate that the reduced pressor response to MTX of the mesenteric vascular bed of PVL rats is due to an endothelial alteration, compatible with an enhanced production of nitric oxide. The lack of response to calphostin C in PVL vessels suggests an impairment in agonist-induced PKC activation. Since direct activation of PKC induces a normal pressor response, it is concluded that the endothelial alteration interacts with the mechanism producing PKC activation, which results in a lower pressor response of the PVL mesenteric vaculature.
AuthorsN M Atucha, M C Ortíz, C Martínez, T Quesada, J García-Estañ
JournalBritish journal of pharmacology (Br J Pharmacol) Vol. 118 Issue 2 Pg. 277-82 (May 1996) ISSN: 0007-1188 [Print] England
PMID8735627 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Adrenergic alpha-1 Receptor Agonists
  • Adrenergic alpha-Agonists
  • Phorbol 12,13-Dibutyrate
  • Protein Kinase C
  • Methoxamine
Topics
  • Adrenergic alpha-1 Receptor Agonists
  • Adrenergic alpha-Agonists (pharmacology)
  • Animals
  • Enzyme Activation
  • Hypertension, Portal (enzymology, physiopathology)
  • Male
  • Methoxamine (pharmacology)
  • Phorbol 12,13-Dibutyrate (pharmacology)
  • Protein Kinase C (metabolism)
  • Rats
  • Rats, Sprague-Dawley
  • Splanchnic Circulation (drug effects, physiology)

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