FURTHER STUDIES ON THE EFFECTS OF RESERPINE PRETREATMENT ON RABBIT AORTA: CALCIUM AND HISTOLOGIC CHANGES

¹ Departments of Pharmacology and Anatomy, Medical College of Virginia, Health Sciences Division, Virginia Commonwealth University, Richmond, Virginia

The present study investigated alterations in tissue calcium and morphology coincident with the relatively nonspecific supersensitivity which had been shown to develop in aortic strips from rabbits after reserpine pretreatment. The schedule of reserpine pretreatment consisted of 0.3 mg/kg/day for three days. After this regime aortic strips from pretreated rabbits were found to be identical to aortic strips from control rabbits with respect to tissue water content, extracellular (sucrose-C¹⁴) space, Ca⁴⁵ tissue space and total calcium content. These findings suggest that the pretreatment schedule had not had a deleterious effect on the tissue. On the other hand, changes were apparent which may be related to the relatively nonspecific supersensitivity. Three parameters were significantly altered after reserpine pretreatment. 1) Efflux of Ca⁴⁵ into Ca-free Ringer's solution from tissue binding sites in the aorta appeared to have been facilitated over a portion of the experiment after reserpine pretreatment. This may reflect a reduction in affinity of calcium binding at membrane sites. Since calcium is probably involved in membrane stability this could result in a reduction in stability and facilitate stimulation by certain agents which alter membrane permeability. 2) Total tissue calcium retention in Ca-free Ringer's solution was significantly greater in aortic strips from reserpine-pretreated rabbits. These calcium levels may reflect calcium accumulation or retention by subcellular fractions which is not readily lost by diffusion. 3) A comparison of tissues viewed by light microscopy revealed morphologic differences which may be related to changes in tissue calcium utilization. It is proposed that these three alterations are in connection with the mechanism for the postsynaptic change responsible for the relatively nonspecific supersensitivity which develops after reserpine pretreatment.