The role of uptake of noradrenaline of its positive inotropic effect in relation to muscle geometry. Statistical evaluation.
1. The influence of saturable drug uptake on the drug concentration near the receptor sites was shown theoretically to depend on the geometry of the preparation; increases in the volume/surface ratio (V/S) of the preparation decrease the sensitivity of the preparation to an agonist inactivated in the tissue. 2. The positive inotropic effect of (-)-noradrenaline was found to depend on the ratio V/S of the preparation; papillary muscles with larger V/S were less sensitive to the drug and showed steeper noradrenaline concentration-effect curves. 3. An algorithm for the statistical estimation of the parameters of the saturable uptake process was derived. It was applied to the positive inotropic noradrenaline effect in relation to muscle geometry. As an analysis of variance showed, the model explained a significant proportion of the shift of (-)-noradrenaline concentration-effect curves associated with variation in size of the preparation.
D000818:Animals; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D008954:Models, Biological; D009132:Muscles / Q000033:anatomy & histology*; D009200:Myocardial Contraction / Q000187:drug effects*; D009638:Norepinephrine / Q000378:metabolism* / Q000494:pharmacology; D010210:Papillary Muscles / Q000033:anatomy & histology; D010539:Permeability; D013268:Stimulation, Chemical
D009638:Norepinephrine