title: α1 -Adrenoceptor activation of PKC-ε causes heterologous desensitization of thromboxane receptors in the aorta of spontaneously hypertensive rats.
abstract: OBJECTIVE
  In the aorta of adult spontaneously hypertensive (SHR), but not in that of normotensive Wistar-Kyoto (WKY), rats, previous exposure to phenylephrine inhibits subsequent contractions to PGE2 . The present experiments were designed to examine the mechanism(s) underlying this inhibition.
  
  
  METHODS
  Isometric tension was measured in isolated rings of SHR and WKY aortae. Gene expression and protein presence were measured by quantitative real-time PCR and Western blotting respectively.
  
  
  RESULTS
  In aorta of 18 weeks SHR, but not age-matched WKY, pre-exposure to phenylephrine inhibited subsequent contractions to PGE2 that were mediated by thromboxane prostanoid (TP) receptors. This inhibition was not observed in preparations of pre-hypertensive 5-week-old SHR, and was significantly larger in those of 36- than 18-week-old SHR. Pre-exposure to the PKC activator, phorbol 12,13-dibutyrate, also inhibited subsequent contractions to PGE2 in SHR aortae. The selective inhibitor of PKC-ε, ε-V1-2, abolished the desensitization caused by pre-exposure to phenylephrine. Two molecular PKC bands were detected and their relative intensities differed in 36-week-old WKY and SHR vascular smooth muscle. The mRNA expressions of PKC-α, PKC-ε, PK-N2 and PKC-ζ and of G protein-coupled kinase (GRK)-2, GRK4 and β-arrestin2 were higher in SHR than WKY aortae.
  
  
  CONCLUSIONS
  These experiments suggest that in the SHR but not the WKY aorta, α1 -adrenoceptor activation desensitizes TP receptors through activation of PKC-ε. This heterologous desensitization is a consequence of the chronic exposure to high arterial pressure.
authors: Department of Pharmacology & Pharmacy and Stake Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong, China.
authors: Yingzi
authors: Y
authors: Zhao
authors: Department of Pharmacology & Pharmacy and Stake Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong, China.
authors: Paul M
authors: PM
authors: Vanhoutte
authors: Department of Pharmacology & Pharmacy and Stake Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong, China.
authors: Susan W S
authors: SW
authors: Leung
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism*; D008297:Male; D051744:Protein Kinase C-epsilon / Q000378:metabolism*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism*; D017482:Receptors, Thromboxane / Q000378:metabolism*
chemical_list: D018340:Receptors, Adrenergic, alpha-1; D017482:Receptors, Thromboxane; D051744:Protein Kinase C-epsilon