Vasoconstrictor threshold synergism and potentiation in the rabbit isolated thoracic aorta

Isolated rings of rabbit thoracic aorta were mounted in tissue baths for the measurement of isometric contraction, and the effects of combinations of two agonists were studied. Concentrations of methoxamine, clonidine, norepinephrine (NE), 5-hydroxytryptamine (5-HT) and potassium causing threshold contraction (0.1 g) were determined. Combinations of any two of these or of two doses of the same agonist elicited far greater than additive contractions ranging from 0.5 to 2.7 g. When dose-response curves to an alpha adrenergic agonist were obtained in the presence of a threshold concentration of the same or another alpha agonist, the curve was shifted to the left at threshold but converged with the control curve between ED10 and ED70. When 5-HT dose-response curves were obtained in the presence of either NE or methoxamine, the curve was shifted to the left in a parallel fashion. Both NE and methoxamine dose-response curves were also shifted to the left in a parallel fashion in the presence of 5-HT. The threshold concentration of potassium caused leftward parallel shifts of the dose-response curves for all agonists studied. These observations are consistent with the conclusion that the resting state of the rabbit thoracic aorta differs from the threshold contractile state and that this accounts for the far greater than additive contraction caused by combinations of two threshold doses of the same or different agonists. The first dose delivers sufficient stimulus to move the tissue from resting to threshold contractile state whereas the stimulus delivered by the second dose manifests entirely as contraction. This phenomenon affects primarily the threshold response.(ABSTRACT TRUNCATED AT 250 WORDS)