Gap junctions modulate tissue contractility and alpha 1 adrenergic agonist efficacy in isolated rat aorta.
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 alpha 1 adrenergic receptor activation in rat aortic rings. Preincubation with the selective junctional uncoupling agent heptanol (200 microM) diminished the magnitude of contractions induced by the low-efficacy partial agonist oxymetazoline (1-3 microM) 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 microM; n = 16 rings from 16 animals). Reduced phenylephrine contractility was observed at higher heptanol concentrations (500 microM). However, neither 200 nor 500 microM 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 alpha 1 adrenergic-receptor activated second-messenger molecules appears to be an important modulator of tissue contractility and agonist efficacy.
Christ
G J
GJ
Department of Urology, Albert Einstein College of Medicine, Bronx, New York.
Brink
P R
PR
Zhao
W
W
Moss
J
J
Gondré
C M
CM
Roy
C
C
Spray
D C
DC
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000438:Alcohols / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology; D003198:Computer Simulation; D017630:Connexins; D004058:Diffusion; D019850:Heptanol; D066298:In Vitro Techniques; D007365:Intercellular Junctions / Q000502:physiology*; D008297:Male; D008565:Membrane Proteins / Q000032:analysis; D010109:Oxymetazoline / Q000493:pharmacokinetics / Q000494:pharmacology; D010656:Phenylephrine / Q000493:pharmacokinetics / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D014661:Vasoconstriction / Q000187:drug effects*
D000316:Adrenergic alpha-Agonists; D000438:Alcohols; D017630:Connexins; D008565:Membrane Proteins; D010656:Phenylephrine; D019850:Heptanol; D010109:Oxymetazoline