Effects of various antihypertensive guanidine derivatives on the adult rat superior cervical ganglion: histology, ultrastructure, and cholinesterase histochemistry.

Abstract

Abstract: A series of postganglionic neurone blocking agents was administered intraperitoneally in large doses for 2‐3 weeks to adult male rats, and the effects on the superior cervical ganglion were investigated. Histologically guanethidine and guanacline induced pronounced changes consisting of chromatolysis of the nerve cells accompanied by an infiltration of small cells. A varying number of ganglion cells completely degenerated. Guanidine, N‐(β‐guanidinoethyl)‐hexahydrobenzo‐[d]‐azocine (Ph 881/7), guanoxan, debrisoquin, bethanidine, brety‐lium, and reserpine did not change the histological picture. Ultrastructural changes of the nerve cells consisting mainly of mitochondrial swelling with partial loss of mitochondrial crests were observed to a major extent following guanethidine and guanacline (with the latter drug furthermore, numerous lipofuscin pigment granules appearing in the cytoplasm), and to a minor extent following bretylium, debrisoquin, bethanidine, and guanoxan. Guanidine, Ph 881/7, and reserpine did not produce any changes. Histochemically demonstrated cholinesterases were diminished following guanethidine and guanacline, mainly from the cytoplasm of the nerve cells. The other guanidinium compounds did not produce changes in the cholinesterases. No structure‐activity relationship was established concerning the ganglionic effects of the drugs. The changes are considered to be cytotoxic effects of the compounds, and the differences in response are assumed to be due to different potency and different extents of accumulation in the sympathetic ganglion nerve cells.