Vasodilatory effects of cholinergic agonists are greatly diminished in aorta from M3R-/- mice

Sandeep Khurana, Ingrid Chacon, Guofeng Xie, Masahisa Yamada, Jurgen Wess, Jean Pierre Raufman, Richard H. Kennedy

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Acetylcholine interacts with endothelial muscarinic receptors to enhance nitric oxide (NO) release and thereby cause vasodilation. The present study was designed to determine if this effect of acetylcholine is mediated by muscarinic M3 receptors. Thoracic aortae were isolated from wild-type (WT) and M3 receptor knock out (M3R-/-) male mice, and endothelium-intact (I) and -denuded (D) aortic rings were bathed in physiological buffer. Preparations were utilized to examine the contractile response to phenylephrine (1×10-8-3×10-4 M added cumulatively) and the vasodilatory actions of acetylcholine (10 -8-10-4 M), carbachol (10-9-10-4 M), ATP (3×10-5 M) and the NO donor SIN-1 (10-4 M), each added in the presence of phenylephrine. Endothelium-dependent vasodilatory effects of acetylcholine and carbachol were obvious in aortae isolated from WT mice (56.3±9.8% and 49.1±4.1% reductions, respectively, in phenylephrine-induced contraction; p<0.05), while acetylcholine and carbachol-associated relaxations observed in endothelium-intact M 3R-/- preparations (17.9±2.6% and 13.5±4.2% reductions, respectively) did not differ significantly from time-control values. ATP-induced, endothelium-dependent vasodilation was similar in preparations from M3R-/- and WT mice, and SIN-1 elicited similar dilatory effects in intact and denuded WT and M3R-/- segments. Phenylephrine concentration-response curves were shifted leftwards by removal of the endothelium in both groups (EC50 values: WT-I/D - 25.59±6.86/3.13±1.01×10-7 M; M3R -/-I/D - 13.92±4.21/1.52±0.46×10-7 M; both p<0.05); however, the phenylephrine response did not differ significantly when compared between the WT and M3R-/- groups. These results indicate that the attenuated vasodilatory effect of acetylcholine in endothelium-intact aortae from M3R-/- mice is due to the absence of muscarinic M3 receptors, and thus suggest that in mouse aorta, muscarinic M3 receptors play a major role in the endothelium-dependent acetylcholine-induced vasodilation.

Original languageEnglish (US)
Pages (from-to)127-132
Number of pages6
JournalEuropean Journal of Pharmacology
Volume493
Issue number1-3
DOIs
StatePublished - Jun 16 2004

Fingerprint

Cholinergic Agonists
Acetylcholine
Endothelium
Aorta
Phenylephrine
Muscarinic M3 Receptors
Carbachol
Vasodilation
Adenosine Triphosphate
Molsidomine
Nitric Oxide Donors
Muscarinic Receptors
Thoracic Aorta
Buffers
Nitric Oxide

Keywords

  • ATP
  • Cholinergic agonist
  • Receptor subtype
  • SIN-1
  • Vascular relaxation

ASJC Scopus subject areas

  • Pharmacology

Cite this

Khurana, S., Chacon, I., Xie, G., Yamada, M., Wess, J., Raufman, J. P., & Kennedy, R. H. (2004). Vasodilatory effects of cholinergic agonists are greatly diminished in aorta from M3R-/- mice. European Journal of Pharmacology, 493(1-3), 127-132. https://doi.org/10.1016/j.ejphar.2004.04.012

Vasodilatory effects of cholinergic agonists are greatly diminished in aorta from M3R-/- mice. / Khurana, Sandeep; Chacon, Ingrid; Xie, Guofeng; Yamada, Masahisa; Wess, Jurgen; Raufman, Jean Pierre; Kennedy, Richard H.

In: European Journal of Pharmacology, Vol. 493, No. 1-3, 16.06.2004, p. 127-132.

Research output: Contribution to journalArticle

Khurana, S, Chacon, I, Xie, G, Yamada, M, Wess, J, Raufman, JP & Kennedy, RH 2004, 'Vasodilatory effects of cholinergic agonists are greatly diminished in aorta from M3R-/- mice', European Journal of Pharmacology, vol. 493, no. 1-3, pp. 127-132. https://doi.org/10.1016/j.ejphar.2004.04.012
Khurana, Sandeep ; Chacon, Ingrid ; Xie, Guofeng ; Yamada, Masahisa ; Wess, Jurgen ; Raufman, Jean Pierre ; Kennedy, Richard H. / Vasodilatory effects of cholinergic agonists are greatly diminished in aorta from M3R-/- mice. In: European Journal of Pharmacology. 2004 ; Vol. 493, No. 1-3. pp. 127-132.
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