EFFECT OF NITRIC-OXIDE SYNTHASE INHIBITION ON CARDIORESPIRATORY RESPONSES IN THE CONSCIOUS RAT

Nitric oxide synthase (NOS) blockade was used to test the cardioventil atory responses to hypercapnia and hypoxia in freely behaving animals. Chronically instrumented adult Sprague-Dawley rats were studied befor e and after intravenous administration of either 100 mg/kg of N-G-nitr o-L-arginine methyl ester (L-NAME), a nonspecific NOS blocker, or 10 m g/kg of S-methyl-L-thiocitrulline (SMTC), a selective neural NOS inhib itor L-NAME injection induced sustained blood pressure (BP) elevation with transient tachycardia and increased minute ventilation (VE), whic h returned to baseline within minutes. SMTC elicited similar, although transient, BP increases; however, heart rate and VE decreased. L-NAME and SMTC did not modify overall steady-state hypercapnic responses. I n control conditions, hypoxia induced early VE increases with further VE enhancements at 30 min. L-NAME increased the early VE response to 1 0% O-2 but induced late VE reductions in hypoxia. SMTC did not change early VE responses but induced marked reductions in the later VE hypox ic responses. In control animals, hypoxia induced a significant heart rate increase. This increase was absent during the early response afte r SMTC and was followed in both L-NAME- and SMTC-treated animals by si gnificant heart rate reductions to values below room air. Similarly, t he sustained BP response to hypoxia in control animals was absent afte r administration of NOS inhibitors. These findings suggest that NOS ac tivity exerts excitatory influences on respiration and cardiac chronot ropy and sustained vasomotor tone during hypoxia. We speculate that NO S-mediated mechanisms may play an important role in hypoxia-induced ve ntilatory roll-off during wakefulness.