Gap junctions modulate tissue contractility and alpha1 adrenergic agonist efficacy in isolated rat aorta

G. J. Christ, P. R. Brink, W. Zhao, J. Moss, C. M. Gondre, C. Roy, D. C. Spray

Research output: Contribution to journalArticle

59 Scopus citations

Abstract

Immunocytochemical analysis, using antibodies directed against connexin43, revealed abundant gap junctions between smooth muscle cells in intact aorta from Fischer 344 rats. Therefore, the authors evaluated the potential contribution of these intercellular junctions to contractile responses elicited by alpha1 adrenergic receptor activation in rat aortic rings. Preincubation with the selective junctional uncoupling agent heptanol (200 μM) diminished the magnitude of contractions induced by the low-efficacy partial agonist oxymetazoline (1-3 μM) by 50.6 ± 4.5% (P < .01; n = 16 rings from 16 rats) but had no effect on equivalent contractions induced by the high-efficacy agonist phenylephrine (0.1 μM; n = 16 rings from 16 animals). Reduced phenylephrine contractility was observed at higher heptanol concentrations (500 μM). However, neither 200 nor 500 μM heptanol altered the magnitude of contractions elicited by 60 mM KCl, indicating that tissue contractility per se was unaffected by heptanol. In calcium-free solution, the magnitude of the phasic contraction induced by phenylephrine was three- fold greater than the magnitude of the oxymetazoline-induced phasic contraction (P < .001) but the phasic responses to both agonists were unaffected by the same heptanol concentrations that significantly diminished their steady-state responses. Because heptanol, at the concentrations used, has selective pharmacological actions on gap junctions, these studies provide additional support for a role of gap junctions in the maintenance and modulation of vasomotor tone. In rat aorta, junctional transfer of alpha1 adrenergic-receptor activated second-messenger molecules appears to be an important modulator of tissue contractility and agonist efficacy.

Original languageEnglish (US)
Pages (from-to)1054-1065
Number of pages12
JournalJournal of Pharmacology and Experimental Therapeutics
Volume266
Issue number2
StatePublished - Jan 1 1993

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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