Effect of acetylcholine on phasic and tonic components of vascular smooth muscle contraction
Watkins, R.W.; Davidson, I.W.
Archives Internationales de Pharmacodynamie et de Therapie 243(2): 217-227
1980
ISSN/ISBN: 0003-9780 PMID: 7377896 Document Number: 165635
The contractile response of vascular smooth muscle to vasoconstrictor agents may consist of phasic (fast) and tonic (slow) components of contraction depending upon the particular agonist. The isometric contractile response of rabbit aortic strips to acetylcholine was studied to determine the agonist's effects on the functional properties of vascular smooth muscle. When contractions produced by a maximally effective agonist concentration were plotted as in velocity vs. time, a characteristic curve described by a 2-term function .ovrhdot.Qt = .vphi.1e-.vphi.2t + .theta.1e-.theta.2t was found. Experiments in Ca-free solution served to identify the 2nd term as the tonic component of contraction. The contraction velocity parameters were determined graphically by exponential stripping: .vphi.1 and .theta.1 represent the velocity of contraction at time zero for the phasic and tonic components, respectively; .vphi.2 and .theta.2 are 1st-order rate constants for their respective components of contraction. The empirical relationship indicates that the phasic and tonic components occur simultanesouly and not sequentially. The relative contribution of phasic and tonic components to total tension developed (Qtot) was estimated by integration to give Qtot = Qphasic + Qtonic where .**GRAPHIC**. Experimentally observed responses to several agonist concentrations were log dose-related and were the sum of both phasic and tonic components. The tonic component of contraction contributed more to total tension development for any given agonist concentration than did the phasic component. However, supramaximal agonist concentrations depressed the tonic component of contraction. The mode of action of acetylcholine-induced contractions of vascular smooth muscle involves simultaneous activation of intracellular (phasic) and extracellular (tonic) Ca stores; these actions are dose-dependent.