Arachidonate Metabolites and Serotonin Contraction of Femoral Arteries from DOCA-salt Hypertensive Rats

Abstract

Kanagy, NL, Mecca TE, Webb RC. Arachidonate metabolites and serotonin contraction of: femoral arteries from DOCA-salt hypertensive rats.

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±7mmHg) 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), KCI (40.1 vs. 27.0 mmol/L) and AIF⁻⁴ (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 KCI or AIF⁻⁴ 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 AIF₄- or KCI in this preparation.

Key Words:

• aluminium fluoride
• phospholipase A₂
• mineralocorticoid hypertension
• prostaglandins
• arachidonate