To investigate whether nitric oxide is involved in the cardiovascular responses mediated via the locus coeruleus, the effects of microinjections of L-arginine and L-glutamate into the locus coeruleus on blood pressure and heart rate were investigated in sodium pentobarbitone-anaesthetized rats. Unilateral microinjection of L-arginine (25, 50 nmol) elicited dose-related depressor (-17 +/- 4, -25 +/- 4 mmHg) and bradycardic (13 +/- 3, 24 +/- 6 b.p.m.) effects. Furthermore, these effects were attenuated by prior local microinjection of N(G)-nitro-L-arginine (40 nmol). Peripheral muscarinic receptor blockade with atropine methyl nitrate (1 mg/kg, i.v.) attenuated the bradycardic but not the depressor responses to L-arginine. L-Glutamate (2 nmol) microinjections also mediated depressor (-27 +/- 6 mmHg) and bradycardic (53 +/- 23 b.p.m.) effects that were attenuated by microinjections of dizocilpine maleate (1 nmol) into the locus coeruleus. In addition, pretreatment with N(G)-nitro-L-arginine (40 nmol) also significantly attenuated the depressor response elicited by L-glutamate. These results suggest that nitrergic and glutamatergic pathways are operative within the locus coeruleus to modulate cardiovascular function, and also that a functional interaction may exist between the nitrergic and glutamatergic systems within the rat locus coeruleus.