title: Contraction velocity analysis of norepinephrine and angiotensin-II activation of vascular smooth muscle.
abstract: The contractile response of vascular smooth muscle is known to consist of fast and slow components of contraction. We investigated the effect of norepinephrine and angiotensin-II on these functional properties of vascular smooth muscle in a quantitative fashion by analyzing the velocity of isometric tension development in rabbit aortic strips as a function of time. Basic premises for contraction velocity analysis are: (1) tension development is proportional to agonist concentration and relates to the amount of calcium fixed by the contractile proteins; (2) the rate of tension development (Qt) reflects the rate calcium is mobilized; (3) the rate at which calcium is made available relates to agonist concentration; (4) calcium is available from internal and external sites; (5) the calcium source)s) activated are characteristic of the mechanism of action of a particular agonist, and (6) the source of calcium activated is identifiable. Aortic strips were contracted maximally with norepinephrine and the velocity of contraction found to decrease with time according to the empirical expression Qt = phi 1e-phi 2t + theta 1e-the 2t. Experiments in calcium-free medium served to identify the tonic component of norepinephrine-induced contraction as the second term while angiotensin demonstrated only one term (phasic) which was independent of extracellular calcium. Strips contracted with different concentrations of norepinephrine or angiotensin showed dose-dependent actions on these functional properties of vascular smooth muscle as revealed by their effects on the contraction velocity parameters. An expression describing the contribution of each component to total tension developed was derived by integrating the above expression to give Qtot = phi 1 (1--e-phi 2tmax)/phi 2 + theta 1 (1--e-theta 2tmax)/theta 2. The contribution of each component to total tension development was donse-dependent and their sum gave the total tension observed experimentally with norepinephrine. For angiotensin, the first term of the preceeding expression gave the observed tension response. It is concluded that contraction velocity analysis affords a new approach for studying the effects of vasoactive agents on the functional properties of vascular smooth muscle.
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D005260:Female; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology*; D011817:Rabbits
chemical_list: D000804:Angiotensin II; D009638:Norepinephrine