Thiopentone-induced changes in the contraction pattern of vascular smooth muscle: the influence of albumin.
The influence of thiopentone on resting tension, contractions evoked by exogenous noradrenaline (NA) and contractions elicited by electrical field stimulation of rings of rabbit pulmonary artery was studied over a concentration range limited by the solubility of the drug. At thiopentone concentrations from 3 X 10(-5) to 1.4 X 10(-3)M in a protein-free electrolyte solution (K-H solution) a gradual increase in resting tension to 232% of the control value was observed. The concentration-effect curve was displaced to the left in the presence of albumin (45 gl-1) at drug concentrations below 1.6 X 10(-4)M. Above that concentration the curve was displaced to the right. The maximal contractile response to exogenous NA in K-H was reduced from 4.1 to 1.8 g by 5.6 X 10(-4)M thiopentone, but the effects of low concentrations of NA were potentiated by thiopentone. The concentration-effect curve for exogenous NA was displaced to the right by albumin itself. The contractions evoked by electrical field stimulation in K-H solution were increased by thiopentone up to 2.4 X 10(-4)M where a maximum of 141% of the control value was reached. Above that a gradual decrease was observed, the height of the contractions being reduced by 75% of the control value at 1.4 X 10(-3)M thiopentone. Thiopentone failed to potentiate electrically-induced contractions in the presence of albumin K-H, and the concentration-effect curve for the inhibitory effect of thiopentone was displaced to the right. 5 From relationships between observed responses and free and total drug concentrations, a procedure was suggested to determine a biologically relevant expression for the thiopentone binding to albumin. The biologically determined albumin binding was always less than the binding determined by equilibrium dialysis, indicating that the fraction of thiopentone bound to albumin could not necessarily be considered biologically inactive.
D000418:Albumins / Q000378:metabolism*; D000818:Animals; D004558:Electric Stimulation; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology*; D011485:Protein Binding; D011651:Pulmonary Artery / Q000187:drug effects / Q000502:physiology; D011817:Rabbits; D013874:Thiopental / Q000378:metabolism / Q000494:pharmacology*
D000418:Albumins; D013874:Thiopental; D009638:Norepinephrine