Nitrergic stimulation of the locus coeruleus modulates blood pressure and heart rate in the anaesthetized rat

Abstract

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.