Acetylcholine causes endothelium-dependent contraction of mouse arteries

Yingbi Zhou, Saradhadevi Varadharaj, Xue Zhao, Narasimham Parinandi, Nicholas A. Flavahan, Jay L. Zweier

Research output: Contribution to journalArticlepeer-review

Abstract

The goal of this study was to determine whether acetylcholine evokes endothelium-dependent contraction in mouse arteries and to define the mechanisms involved in regulating this response. Arterial rings isolated from wild-type (WT) and endothelial nitric oxide (NO) synthase knockout (eNOS-/-) mice were suspended for isometric tension recording. In abdominal aorta from WT mice contracted with phenylephrine, acetylcholine caused a relaxation that reversed at the concentration of 0.3-3 μM. After inhibition of NO synthase [with Nω-nitro-L-arginine methyl ester (L-NAME), 1 mM], acetylcholine (0.1-10 μM) caused contraction under basal conditions or during constriction to phenylephrine, which was abolished by endothelial denudation. This contraction was inhibited by the cyclooxygenase inhibitor indomethacin (1 μM) or by a thromboxane A2 (TxA2) and/or prostaglandin H2 receptor antagonist SQ-29548 (1 μM) and was associated with endothelium-dependent generation of the TxA2 metabolite TxB 2. Also, SQ-29548 (1 μM) abolished the reversal in relaxation evoked by 0.3-3 μM acetylcholine and subsequently enhanced the relaxation to the agonist. The magnitude of the endothelium-dependent contraction to acetylcholine (0.1-10 μM) was similar in aortas from WT mice treated in vitro with L-NAME and from eNOS-/- mice. In addition, we found that acetylcholine (10 μM) also caused endothelium-dependent contraction in carotid and femoral arteries of eNOS-/- mice. These results suggest that acetylcholine initiates two competing responses in mouse arteries: endothelium-dependent relaxation mediated predominantly by NO and endothelium-dependent contraction mediated most likely by TxA2.

Original languageEnglish (US)
Pages (from-to)H1027-H1032
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume289
Issue number3 58-3
DOIs
StatePublished - Sep 2005
Externally publishedYes

Keywords

  • Cyclooxygenase
  • Endothelial nitric oxide synthase
  • Endothelium-derived contracting factor
  • Gene knockout

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Fingerprint Dive into the research topics of 'Acetylcholine causes endothelium-dependent contraction of mouse arteries'. Together they form a unique fingerprint.

Cite this