A role for nitric oxide in endotoxin-induced depletion of the peripheral catecholamine stores

Endotoxemia is associated with increased sympathetic nerve activity and dep letion of norepinephrine (NE) and epinephrine (EPI) contents in the adrenal gland and in sympathetically innervated tissues. Endotoxin (bacterial lipo polysacchride [LPS]) causes an increased production of nitric oxide (NO) by inducing nitric oxide synthase (iNOS) expression in various tissues. This increased production of NO contributes significantly to the hypotension ass ociated with endotoxemia. At high concentrations, NO also can act as a neur otoxin. In this study we tested the hypothesis that increased production of NO is involved in depletion of catecholamine content in various tissues fr om rats treated with a nonlethal dose of LPS. Catecholamine content was mea sured by high-performance liquid chromatography with electrochemical detect ion (HPLC-EC) and NOS activity was measured by the H-3-l-arginine to H-3-l- citrulline conversion method. The NE content was decreased in rat adrenal g land, lung, spleen, tail artery, and aorta after LPS. The maximal decrease was at 24 h and returned to control levels at 6 days (144 h). There was no depletion of the NE content in the heart. The EPI content in the adrenal gl and was greatly depleted (91%) from 12 to 72 h after LPS. LPS increased the NOS activity in all tissues examined. The time course for NOS activity sho wed an increase at 3 h, a further increase at 6 h, and a return to control level at 48 h after LPS. The increase in NOS activity occurred before maxim al catecholamine depletion. Aminoguanidine, a relatively selective iNOS inh ibitor, completely prevented NE depletion in all tissues and partially prev ented adrenal EPI depletion induced by LPS. These results are consistent wi th the hypothesis that LPS-induced production of NO plays a role in depleti on of tissue NE and EPI.