Involvement of Nitric Oxide in the Medullary Control of Circulation in Normotensive Rats

In acute experiments on anesthetized (urethane) normotensive rats, we studied the hemodynamic effects of unilateral microinjections of a nitric oxide (NO) donor, sodium nitroprusside, into the medullary nuclei participating in central cardiovascular control. We studied also the effects of modulation of the intensity of NO production: enhancing its synthesis by intramedullary injections of exogenous L-arginine or inhibiting this process with an inhibitor of neuronal NO synthase (nNOS), L-NNA, or with an inhibitor of arginase, norvaline. Intramedullary injections of the above agents were confined to the nucleus of the tractus solitarius, dorsal motor nucleus of the vagus, nucleus ambiguous, and lateral reticular nucleus. We tried to evaluate the possibility of production of NO from L-arginine in central neurons of normotensive rats via not only the well-known NO synthase pathway, but also via an alternative arginase-mediated pathway of metabolism of the above amino acid. Our results demonstrated that both enzymes are potentially active: injections of the mentioned inhibitors of the enzymes into the medullary neuronal structures induced marked shifts in the systemic arterial pressure (SAP), the integrative parameter characterizing the state of the cardiovascular system. After preliminary administration of an nNOS inhibitor, 7-nitroindazole (30 mg/kg, i.p.) or an inhibitor of arginase, norvaline (2 [mu]g, i.v.), injections of L-arginine into the medullary nuclei failed to evoke significant shifts in the SAP. We suggest that the comparative degree of activation of nNOS or arginase in the medullary nuclei depends on different factors, first of all on the level of oxygenation of the nerve tissue. An inverse dependence is likely to exist between the levels of activation of the above enzymes.