Effects of ethylene glycol dinitrate on pituitary-adrenocortical function in the rat

Abstract

A single sc injection of 65 mg/kg ethylene glycol dinitrate (EGDN) in the rat leads to a marked increase in plasma corticosterone, rising to a maximum at 15 min and persisting for over 2 h. The response is dependent on the pituitary, the initial stimulus probably being the systemic hypotension resulting from the EGDN injection. The corticosterone output in response to an injection of EGDN given 24 or 72 h after the last of a series of injections is markedly reduced. Repeated injections of EGDN also lead to a decrease in the corticosterone response to a “standard” stress (histamine ip) given 24, 48 and 72 h after the last of the series of EGDN injections. It is suggested that the reduced corticosterone response to EGDN following a series of injections is due partly to tolerance to the hypotensive action of EGDN and partly to some deficiency in the hypothalamopituitary-adrenal axis.