Adverse effects of tris hydrochloride, a commonly used buffer in physiological media.

1. Tris 10mM, produced inhibition of motor responses to adrenergic motor nerve stimulation in all smooth muscles studied (rat anococcygeus and vas deferens perfused rabbit ear artery). Up to 30 mM Tris was without significant effect on those motor responses to cholinergic nerve stimulation examined (guinea-pig ileum). 2. a similar reduction in responses to endogenous motor agonists was seen only in the anococcygeus, while in the rabbit ear artery, responses to noradrenaline (NA) were potentiated. 3. tris consistently produced increased tone in the rat anococcygeus and rabbit aorta, but in no other tissue, Small reductions in tone were seen with Tris in spiral strips of rabbit ear artery. 4. inhibitory responses to adrenergic nerve stimulation and to NA in the rabbit jejunum and to inhibitory nerve stimulation in the rat anococcygeus were unaffected by Tris. 5. in the perfused rabbit heart Tris produced a negative inotropic effect and reduced responses to vagal stimulation. Responses to sympathetic nerve stimulation and to ACh and NA were not significantly altered. 6. up to 40 mM Tris had little effect on responses of the rat diaphragm to motor nerve stimulation. 7. the effects of Tris on the rat anococcygeus were not reduced by increased calcium levels but were reduced at lower incubation temperatures. The negative inotropic effect of Tris on the rabbit heart was also reduced at lower temperatures. 8. the buffer HEPES produced a reduction in responses to stimulation in the rat anococcygeus and vas deferens along, but at higher concentrations than those of Tris. Increases in tone in the anococcygeus and aorta were never seen with HEPES. 9. These results indicate that Tris in concentrations commonly used as a buffer in physiological salines can exert toxic effects on neuro-muscular transmission in smooth and cardiac muscle though not in skeletal muscle. The effects are variable, mainly presynaptic and appear to affect in particular motor and especially adrenergic transmission. They may be associated with intracellular metabolic actions of Tris.