Effects of competitive antagonists on phasic and tonic components of vascular smooth muscle contraction

Phasic and tonic components of contraction are functional properties of vascular smooth muscle reflecting, respectively, release of intracellular calcium and utilization of extracellular calcium. Recently, it has been appreciated that different agonists may manifest discrete actions on these functional properties of vascular smooth muscle. We have analyzed the contractile response of rabbit aortic strips in response to maximal effective concentrations of the agonists norepinephrine, angiotensin II and acetylcholine in the absence and presence of their specific antagonists: phentolamine, saralasin and atropine in order to determine the actions of the antagonists on these functional properties of vascular smooth muscle. When contractions produced by norepinephrine or acetylcholine were plotted as ln velocity vs. time, characteristic curves described by a two-term function Qt = phi 1e-phi 2t + theta 1e-theta 2t were found (Qt = velocity at any time t: phi 1 and theta 1 are velocity of contraction at zero time for phasic and tonic components; phi 2 and theta 2 are contraction velocity constants for their respective components of contraction). The first term represents the phasic component and the second term the tonic component of contraction. The contraction velocity parameters were different for norepinephrine and acetylcholine. Angiotension II-induced contractions gave velocity curves described by a single term, i.e. phasic component of contraction. Phentolamine blocked completely the tonic component and the decreased tension achieved with norepinephrine was completely accounted for by inhibition of the tonic contribution to total tension development. Atropine completely blocked acetylcoholine's tonic component and also attenuated slightly the phasic component. Saralasin reduced angiotensin II-induced tension development and contraction velocity analysis suggested a non-competitive action. We conclude that competitive antagonists may exert distinct actions on the phasic and tonic components of vascular smooth muscle contraction.