Inhibition of nitric oxide synthase in the hypothalamus blocks the increase in plasma prolactin induced by intraventricular injection of interleukin-1 alpha in the rat.

Injection of interleukin-1 (IL-1) into the third cerebral ventricle (3V) of conscious rats increases plasma prolactin (PRL) concentration. Nitric oxide (NO) is involved in control of corticotropin-releasing factor (CRF) and luteinizing hormone-releasing hormone (LHRH) release. Consequently, we evaluated its role in the PRL-releasing action of IL-1. In the present experiment, NG-mono-methyl-L-arginine (NMMA) (1 mg in 5 microliters of 0.9% NaCl (saline)], an inhibitor of NO synthase, or 5 microliter of saline was microinjected into the 3V of conscious, castrate male rats and blood samples were removed from jugular catheters just prior to and at 10-min intervals after injection. A second injection of NMMA or saline was given 60 min after the first. Five minutes after the injection of NMMA or saline, IL-1 alpha (0.6 pmol in 2 microliter saline), or an equal volume of saline, was injected into the 3V. Plasma PRL concentrations were increased within 10-20 min after injection of IL-1 alpha and a second pulse of PRL usually occurred at 60-70 min following its injection. The maximal increase in plasma PRL from the initial value in the animals injected with IL-1 alpha was highly significant, whereas there was no significant increase in the animals injected with NMMA plus IL-1 alpha or in the animals injected with saline or NMMA. The area under the plasma PRL curve was significantly elevated in the animals injected with IL-1 alpha above that of rats injected with NMMA plus IL-1 alpha during the first hour after injection.(ABSTRACT TRUNCATED AT 250 WORDS)