Arachidonate metabolites and serotonin contraction of femoral arteries from DOCA-salt hypertensive rats

Nancy L. Kanagy, Thomas E. Mecca, R. Clinton Webb

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Serotonin stimulates phospholipase A2 (PLA2) leading to the production of prostaglandin products, several of which are vasoconstrictors. We hypothesised that the elevated vascular responsiveness to serotonin in deoxycorticosterone acetate (DOCA)-hypertensive rats is due in part to augmented production of vasoconstrictor cyclooxygenase products (e.g. PGF(2α)). Denuded helical strips of femoral arteries from DOCA-salt hypertensive rats (SBP = 183 ± 7 mmHg) and normotensive control rats (SBP = 115 ± 2) were used in all experiments. EC50 values for several agonists were significantly reduced in DOCA arteries compared with controls (in μmol/L, control vs. DOCA): PGF(2α) (0.99 vs. 0.23), PGE2 (0.72 vs. 0.22), arachidonate (1.52 vs. 0.73), serotonin (0.19 vs. 0.07), noradrenaline (0.029 vs. 0.013), KCl (40.1 vs. 27.0 mmol/L) and AlF4- (2.3 vs. 1.4 mmol/L). Treatment with indomethacin (14 μmol/L) inhibited the responses to serotonin in DOCA arteries (EC50 values = 0.07 untreated vs. 0.70) and eliminated the responses to arachidonate but did not affect KCl or AlF4- contractions. Cyclooxygenase inhibitors shifted concentration response curves to serotonin in sham and DOCA tissues equally. Thus increased sensitivity to serotonin in DOCA arteries persisted following cyclooxygenase blockade. Therefore, although arachidonate products contribute to the serotonergic contraction in femoral arteries, the augmented response in arteries from DOCA hypertensive rats is not due to increased production of or sensitivity to cyclooxygenase products. Furthermore, arachidonate metabolites do not contribute to the contraction induced by either AlF4- or KCl in this preparation.

Original languageEnglish (US)
Pages (from-to)113-120
Number of pages8
JournalBlood Pressure
Volume5
Issue number2
DOIs
StatePublished - Mar 1996
Externally publishedYes

Keywords

  • aluminium fluoride
  • arachidonate
  • mineralocorticoid hypertension
  • phospholipase A
  • prostaglandins
  • serotonin

ASJC Scopus subject areas

  • Internal Medicine
  • Cardiology and Cardiovascular Medicine

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