Endothelium-independent relaxations to acetylcholine and A23187 in the human umbilical artery

Research output: Contribution to journalArticle

26 Citations (Scopus)


The effects of acetylcholine (ACh) and A23187 on ring preparations from the human umbilical artery (HUA) were investigateds and compared with the rat aorta (RA). The results from the HUA demonstrate that: (1) At both high (pO2>600 mm Hg) and low O2 tension (pO2<55 mm Hg), ACh and A23187 relaxed precontracted rings in a concentration-dependent and endothelium-independent manner. Changes in pO2 did not influence the response of the HUA to either relaxant. (2) Relaxation responses of the HUA to either ACh or A23187 were insensitive to methylene blue (50 μM), L-nitro-arginine methyl ester (100 μM), indomethacin (10 μM) and nordihydroguaiaretic acid (50 μM). Relaxations initiated by ACh were also atropine-resistant. (3). Meclofenamic acid (3 μM) suppressed the relaxations to A23187, but not ACh. (4) Regardless of pO2 superoxide dismutase (100 U/ml) potentiated the relaxant effects of ACh, whereas mannitol (60 mM) enhanced ACh-initiated relaxations at high but not low pO2. (5) Ouabain (30 nM), high potassium (HK+, 60 mM) and tetraethylammonium (20 mM) inhibited responses to ACh. (6) Na+-free physiological saline solution inhibited both relaxations and oscillations initiated by either ACh or A23187. (7) Both nitroglycerin and exogenous nitric oxide (NO) fully, and 8-bromoguanosine 3',5'-cyclic monophosphate partially, relaxed the HUA, and LY83583 (10 μM) reversed such relaxations. (8) In the RA, relaxation responses to ACh and A23187 were endothelium-dependent and sensitivity was reduced under high versus low pO2 conditions. We conclude that in the HUA, unlike in the RA, ACh and A23187 mediate their responses via an endothelium- and NO-independent process(es), perhaps involving the release of a msucle-derived relaxing factor. ACh-initiatedd relaxations are mediated by activation of Na+,K+-ATPase, and subsequent hyperpolarization via K+ efflux, whereas A23187-mediated relaxations result from the synthesis of an indomethacin-resistant cyclooxygenase product.

Original languageEnglish
Pages (from-to)92-105
Number of pages14
JournalJournal of Vascular Research
Issue number2
Publication statusPublished - 1994
Externally publishedYes



  • A23187
  • Acetylcholine
  • Contraction
  • Endothelium
  • Human umbilical artery
  • Oxygen tension
  • Relaxation

ASJC Scopus subject areas

  • Physiology

Cite this